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Brief Overview of a Decade of Genome-Wide Association Studies on Primary Hypertension.

1. Introduction

Hypertension is highly prevalent globally. The estimated number of people with uncontrolled hypertension is nearly 1 billion (around 15% of the world population), with the number predicted to increase to 1.56 billion by the year 2025 [1]. Due to its high prevalence, hypertension is the leading risk factor for cardiovascular disease, stroke, and end-stage kidney diseases. The increased risk of cardiovascular mortality and morbidity has led to the estimation that hypertension causes 13% of all deaths (around 7.5 million deaths worldwide) [2]. Patients are considered to have hypertension when their systolic blood pressure is >140 mmHg and/or their diastolic blood pressure is >90 mmHg [3]. However, raised blood pressure, even within the normal range, is positively and continuously related to mortality and morbidity--each increment of 20 (systolic)/10 (diastolic) mmHg of blood pressure doubles the risk of cardiovascular diseases [2]. Hence, the number of people at risk is higher as the prevalence of raised blood pressure for adults (aged [greater than or equal to]25 years) is around 40% [2].

The majority of hypertension in the general population occur idiopathically with no apparent causes and therefore are categorized as primary hypertension. The remaining hypertensive cases (about 5%) are categorized as secondary hypertension as the raised blood pressure occur secondary to other causes/diseases, for example, hypertension due to aldosteronism, pheochromocytoma, renovascular diseases, or even Mendelian forms of hypertension [4, 5]. However, despite being classified as having no apparent cause, studies of familial aggregation on primary hypertensive patients have found associations of blood pressure among siblings and between parents and children, indicating that genetic factors contribute to the high blood pressure among primary hypertensive patients. Genetic factors have been estimated to explain 30-50% of the interindividual variation in blood pressure which significantly predisposes family (siblings/ children) of primary hypertensive patients to hypertension [6]. These heritable genetic factors, in addition to environment and demographic factors, play a major role in interindividual variation in blood pressure [7]. Therefore, extensive genetic research has been conducted over the years, including genome-wide association studies (GWASs), to help elucidate primary hypertension's heritability.

2. Outcomes of Genome-Wide Association Studies on Primary Hypertension

GWASs have identified over three hundred plus SNPs/loci associated with blood pressure and/or primary hypertension over the past decade (Table 1). Meta-analyses of GWASs have made the biggest contribution as they allowed for larger sample sizes and more extensive imputation panels. Despite these advancements, genetic variation identified so far only explains ~3-6% of the variance for blood pressure, approximately 1 mmHg per allele systolic blood pressure or 0.5 mmHg per allele diastolic blood pressure [8-12]. Further, the vast majority of GWASs were performed predominantly in Caucasian populations with only a few studies assessing or replicating in other populations even though high blood pressure burden risk is ranked number one in Southeast Asia, Central Asia, North Africa, and Middle East [13-40]. This suggests the existence of many more undiscovered SNPs/loci or at the very least SNPs unique to other populations that are not of Caucasian ancestry. For example, one meta-analysis on Oriental populations found five Oriental-specific loci near CAPZA1, FIGN, ENPEP, NPR3, and PTPN11 (near C12orf51) associated with hypertension [22]. Either the differences in environmental exposures/lifestyle factors or genetic background can explain why ethnic/racial susceptibility loci exist. Nevertheless, as even a small increase in blood pressure can increase the risk of cardiovascular diseases, the biological pathways identified by these SNPs would still be useful in resolving many of the open questions regarding blood pressure pathophysiology.

3. Biological Pathways Involved with Blood Pressure Pathophysiology

Mendelian forms of hypertension and germline mutations causing early-onset hypertension have highlighted biological pathways that involve renal salt handling (WNK1, WNK4, KLHL3, and CUL3), ion transport (CACNA1D, CACNA1H, KCNJ5, SCNN1B, and SCNN1G), corticosteroidogenesis (CYP11B2, HSD11B2, NR3C2, CYP11B1, and CYP17A1), and vascular tone (PDE3A) to regulate blood [41-44]. Thus, not surprisingly, GWASs have identified SNPs in or near to genes involved with these biological pathways associated with primary hypertension. In fact, one of the first few high-throughput genotyping was performed on only genes underlying monogenic hypertension and hypotension (not genome-wide) which found two renal sodium regulatory genes (KCNJ1 and NR3C2) to have SNPs associated with blood pressure in the general population [45].

3.1. Renal Salt Handling. One interesting SNP putatively involving renal salt-handling pathway was only linked to hypertension in an extreme case-control GWAS design [25]. This SNP, rs13333226, on chromosome 16 is in the 5' region of UMOD (combined P value of 3.6 x [10.sup.-11]). The minor G allele of this SNP had an OR of 0.87 (95% CI: 0.84-0.91) for hypertension, with the subject having the minor G allele having decreased urinary uromodulin and better renal function. The exclusive expression of uromodulin, the protein encoded by UMOD, in the thick portion of the ascending limb of Henle suggests that the SNP exerts its effect through sodium homeostasis [25]. Also based on renal expression, SNPs in or near to PAPPA2 and ADAMTS7 (rs61823001 andrs62011052, resp., [8]) are expected to play a role in the renal salt-handling pathway. Interestingly in regard to the protein encoded by ADAMTS7, angiotensin II stimulation induced renal expression of the protein [46]. Similarly, renal cortex expression of PAPPA2 in Dahl salt-sensitive rats responded to changes of salt diet supporting a role of the SNP in the renal salt-handing pathway [47]. SNPs in FAM186B and ARHGAP24 on the other hand are postulated to play a role in renal function based on involvement with kidney diseases. Combining whole exome sequencing and homozygosity mapping in consanguineous families, FAM186B was identified as a novel candidate gene for monogenic, recessive nephronophthisis-related ciliopathies [48]. ARHGAP24 on the other hand is thought to play a role in renal cell carcinoma and focal segmental glomerulosclerosis most likely through RhoA and Rac1 signaling pathways [49, 50].

3.2. Ion Transport. Several SNPs in genes involved with ion transport have been associated with blood pressure (e.g., ATP2B1, CACNA1D, CACNA2D2, CACNB2, KCNK3, SLC4A7, and SLC39A8; Table 1). Of these, the one most studied and replicated are SNPs in ATP2B1 [9, 18, 22, 51]. Confirming the role of ATP2B1 in blood pressure regulation is the vascular smooth muscle cell-specific knockout of ATP2B1 mice which had higher systolic blood pressure and significantly increased phenylephrine-induced vasoconstrictions [52]. Similarly, silencing of ATP2B1 through injection of an SiRNA complex into mouse tail veins led to an increase in blood pressure and an increase in contractile response to phenylephrine [53]. These results support that ATP2B1 genetic variants are the causative gene for the association with blood pressure seen in GWASs. The other gene encoding an ion channel with significant supporting evidence is CACNA1D. This is because gain of function mutations in CACNA1D have been found to be causal for primary aldosteronism and for aldosterone-producing cell clusters [42, 54, 55]. As aldosterone is a key regulator of blood pressure, even small changes which may not pass the clinical threshold for primary aldosteronism may be causal for increase in blood pressure. Elevation of aldosterone may also be the mechanism of action for the other ion channels associated with primary hypertension as mutations in the ATPase [Na.sup.+]/[K.sup.+] transporting subunit alpha 1 and G protein-activated inward rectifier K+ channel 4 have also been found causal for primary aldosteronism and aldosterone-producing cell clusters [55,56].

3.3. Corticosteroidogenesis. Surprisingly in the sense that corticosteroids can highly affect blood pressure, only 2 cytochrome P450 enzyme genes involved with corticosteroidogenesis have been linked to hypertension by GWASs--CYP17A1 and CYP21A2. And of that, only SNPs in the CYP17A1 gene have been replicated, though even then with inconsistent results. CYP17A1 encodes 17a-hydroxylase which is essential to the synthesis of cortisol precursors. Therefore, alteration of this gene can cause a deficiency in 17a-hydroxylase and thus cortisol, which affects blood pressure [57]. Supporting the role of CYP17A1 in blood pressure regulation is the SNP rs11191548, a SNP near the CYP17A1 gene that has been consistently associated with blood pressure in both East Asian cohorts and Caucasian cohorts [10, 17, 18, 58-60]. Patients harboring the risky C allele had lower PRA and K+ levels similar to patients with 17a-hydroxylase deficiency, suggesting that the SNP (which is actually in the noncoding region of the gene CNNM2) has an effect on the enzymatic activity of CYP17A1 [58]. One hypothesis as to why inconsistent results occur with GWAS is if the association found between the lead SNP is indirect whereby the signal produced is actually caused by a synthetically linked rarer variant in linkage disequilibrium with the identified tag SNP. This could be the case with the lead SNP rs1004467 which was identified from the CHARGE + Global BPgen metaanalysis [9]. In an Oriental cohort (from Korea), rs1004467 was found to have a modest association with hypertension in prediabetic subjects and a significant association with augmentation index in diabetic subjects [61]. However, in another Oriental cohort with similar ethnic background (from China), rs1004467 association with hypertension/ blood pressure was not found in children [62]. As such, perhaps the causal SNP is not rs1004467 as identified by the initial GWAS meta-analysis but a tag SNP with poor penetrance. Interestingly, rs1004467 is in linkage disequilibrium with rs138009835, a functional SNP located 1800 bases upstream of the transcription site of CYP17A1. In vitro gene reporter gene assays and clinical functional experiments found the minor alleles to have reduced mRNA expression of CYP17A1 and reduced aldosterone excretion [63]. To note, both rs1004467 and rs11191548 are associated with a reduction in both visceral and subcutaneous fat mass in Japanese women [64].

3.4. Vascular Tone. Interestingly, although only one of the fifteen monogenic hypertension genes is postulated to mediate an effect through the vasculature, SNPs associated with blood pressure and primary hypertension are enriched in genes that are expressing their proteins in vascular smooth muscle and endothelial cells [11,12,65-67]. This is consistent with vascular tone playing a primary role in blood pressure regulation. Many of these genes, however, may have been reported as the causal genes due to their proximity to the SNP in question and their likelihood of playing a role in blood pressure regulation rather than due to real functional data [68]. For example, the reported gene for rs7129220, a SNP downstream to the ADM gene in the noncoding RNA CAND1.11 gene, was the ADM gene as adrenomedullin the protein encoded by ADM plays a role in vasodilation [69]. Oppositely, the reported genes for rs633185 are FLJ32810-TMEM133, even though the SNP is within the intron of ARHGAP42 (Table 1). As a candidate gene for blood pressure regulation, ARHGAP42 has many functional evidence to be the causal gene as reduced expression of ARHGAP42 in mice elevated blood pressure [70]. To note, rs633185 is in high linkage disequilibrium with rs604723, another SNP in the intron of ARHGAP42, and the minor T allele is a functional variant that increases ARHGAP42 expression by promoting serum response factor binding to a smooth muscle-selective regulatory element [71]. Based on this strong functional data, rs604723 is most likely the causative SNP at this locus. rs6271 in exon 11 of the DBH gene on the other hand is one of the rare times where GWASs had managed to directly identify a missense variant which is probably damaging to the protein dopamine [beta]-hydroxylase according to PolyPhen-2 prediction [72]. Concurringly, severe orthostatic syndrome (postural hypotension) were found to be caused by truncating, splice site, or missense mutations in the DBH gene [73].

4. Conclusion

Although some of the SNPs identified by GWAS on primary hypertension associates with similar biological pathways as Mendelian or early-onset forms of hypertension (validating the study approach), none of the SNPs identified had a large size effect (< 1 mmHg) to be of significance to an individual patient. The ultimate goals of performing these GWASs are to determine the genetic factors regulating blood pressure that can be used to make predictions about who is at risk of developing hypertension and to identify the biological pathways of the disease allowing for identification of novel targets for treatment or even prevention strategies. As currently no direct clinical application of these GWAS findings can be made, it is still debatable whether GWAS is the best approach to identify the biological underpinnings of primary hypertension. Even though yet-to-be-discovered Oriental-specific loci or rare SNPs that might have larger effect size may increase the variance for blood pressure that can be explained by genetic variation, information on epigenetic modulation (e.g., DNA methylation, posttranslational modifications of proteins, or even gut microbiota [20, 74-78]) may still be needed to explain the total heritability of raised blood pressure which cannot be captured by GWASs.

https://doi.org/10.1155/2018/7259704

Conflicts of Interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

Acknowledgments

The authors thank Ms. Syahirah Kaja Mohideen for her help in preparing this manuscript. Elena Aisha Binti Azizan's research was supported by the Malaysian Minister of Higher Education grant (FRGS/1/2015/SKK08/UKM/02/3). Afifah Binti Azam's salary is supported by the National University of Malaysia (UKm) grant (GUP-2016-083) awarded to Elena Aisha Binti Azizan.

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[75] V. V. Lima, C. S. Rigsby, D. M. Hardy, R. C. Webb, and R. C. Tostes, "O-GlcNAcylation: a novel post-translational mechanism to alter vascular cellular signaling in health and disease: focus on hypertension," Journal of the American Society of Hypertension, vol. 3, no. 6, pp. 374-387, 2009.

[76] F. Z. Marques, C. R. Mackay, and D. M. Kaye, "Beyond gut feelings: how the gut microbiota regulates blood pressure," Nature Reviews Cardiology, vol. 15, no. 1, pp. 20-32, 2017.

[77] J. Li, F. Zhao, Y. Wang et al., "Gut microbiota dysbiosis contributes to the development of hypertension," Microbiome, vol. 5, no. 1, p. 14, 2017.

[78] R. Fan, S.-Q. Mao, T.-L. Gu et al., "Preliminary analysis of the association between methylation of the ACE2 promoter and essential hypertension," Molecular Medicine Reports, vol. 15, no. 6, pp. 3905-3911, 2017.

Afifah Binti Azam [ID] and Elena Aisha Binti Azizan [ID]

Department of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur, Malaysia

Correspondence should be addressed to Elena Aisha Binti Azizan; elena.azizan@ukm.edu.my

Received 28 October 2017; Accepted 12 December 2017; Published 30 January 2018

Academic Editor: Raffaele Pezzani
Table 1: Loci associated with blood pressure and-or hypertension that
have been identified through large-scale studies in the past decade.

Locus name                  SNP       Chr       Chr       Coded
                                      ID     position     allele

2q36.3                   rs2972146     2    226,235,982     T
7q32.1                   rs4728142     7    128,933,913     A
ABHD17C                 rs35199222    15    80,720,696      A

ABHD17C                 rs11634851    15    80,736,624      G
ABLIM3-SH3TC2            rs9687065     5    149,011,577     A
ACE                       rs4308      17    63,482,264      A

ACOX1                    rs2467099    17    75,952,964      T

ADAMTS7-MORF4L1         rs62012628    15    78,777,658      T

ADAMTS7-MORF4L1         rs62011052    15    79,156,983      C
ADAMTS8                 rs11222084    11    130,403,335     T
ADAMTS9                  rs918466      3    64,724,577      A
ADCY3                   rs55701159     2    24,916,727      T
ADM                      rs360157     11     9,732,674      T
ADM                      rs7129220    11    10,350,538      A
ADM                      rs7129220    11    10,350,538      A
ADO                     rs10995311    10    62,805,174      G

ADRB1                    rs2782980    10    114,021,768     T
ADRB1-RNU6-709P         rs10787517    10    114,055,047     A
AGT                      rs2004776     1    230,712,956     T
AKT2                     rs9710247    19    40,254,542      G
AMH-SF3A2                rs740406     19     2,232,222      A
ARHGAP12                rs10826995    10    31,793,730      T

ARHGAP24                 rs2014912     4    85,794,517      T
ARNTL                    rs900145     11    13,272,358      G
ARVCF                   rs12628032    22    19,980,457      T

ARVCF                    rs4819852    22    20,000,644      A
ATP2B1                   rs2681472    12    89,615,182      A
ATP2B1                   rs2681492    12    89,619,312      T
ATP2B1                  rs17249754    12    89,666,809      A
BAT2-BAT5                rs805303      6    31,648,589      G
BDNF                    rs11030119    11    27,706,555      A

BLK-GATA4                rs2898290     8    11,576,400      C
C10orf107                rs4590817    10    61,707,795      C
C10orf107                rs1530440    10    61,764,833      T
C10orf32,                rs4409766    10    102,856,906     T
C10orf32-ASMT
C17orf82-TBX2            rs2240736    17    61,408,032      T
C20orf187                rs1887320    20    10,985,350      A
C2orf43                  rs2289081     2    20,682,080      C

C5orf56                  rs2188962     5    132,435,113     T

CACNA1D                  rs9810888     3    53,601,568      G
CACNA2D2                 rs743757      3    50,438,947      C

CACNB2                   rs1813353    10    18,418,519      C
CACNB2                  rs11014166    10    18,419,869      A
CAMKV-ACTBP13           rs36022378     3    49,876,272      T

CAPZA1                  rs10745332     1    112,646,431     A
CASC15                   rs6911827     6    22,130,372      T

CASZ1                    rs880315      1    10,736,809      T
CCDC141                 rs79146658     2    178,921,341     T

CCDC41-CEP83-           rs139236208   12    94,486,966      A
RN7SL483P
CCNE1                   rs62104477    19    29,804,084      T

CD34                    rs12731740     1    207,851,475     T
CDC42BPA                rs10916082     1    227,064,925     A
CDH13                    rs7500448    16    83,012,185      A

CDH17                    rs2446849     8    94,091,269      T
CELA2A                   rs1042010     1    15,467,418      A

CELA2A                   rs3820068     1    15,471,702      A
CEP164                    rs8258      11    117,412,960     T

CEP68                   rs74181299     2    65,056,838      T

CERS5                    rs7302981    12    50,144,032      A

CFDP1                   rs11643209    16    75,297,146      T

CHIC2                    rs871606      4    53,933,078      T
chr15mb95               rs12906962    15    94,768,842      T

chr1mb25                 rs6686889     1    24,703,979      T
chr1mb9                  rs9662255     1     9,381,890      A

CHST12-LFNG              rs2969070     7     2,472,910      A
CMIP                     rs8059962    16    81,540,592      T
CNNM2                   rs11191548    10    103,086,421     C
COL21A1                  rs1925153     6    56,237,982      T
CPEB4                   rs72812846     5    173,950,633     A

CRACR2B                  rs7126805    11      828,916       A
CRK                     rs12941318    17     1,430,304      T

CRYAA-SIK1-RRP1B        rs12627651    21    43,340,723      A

CSK                      rs1378942    15    74,785,026      A
CYB561-LOC342541         rs4459609    17    63,471,587      A
CYP17A1-NT5C2            rs1004467    10    102,834,750     A

CYP1A1-ULK3              rs6495122    15    74,833,304      A

CYP2C19                  rs4494250    10    94,804,000      A
DBH                       rs6271       9    133,657,152     T
DNM3                    rs12405515     1    172,388,301     T

DPEP1                    rs1126464    16    89,637,957      C

EBF1                    rs11953630     5    158,418,394     T
EBF2                     rs6557876     8    26,043,159      T
ENPEP                    rs6825911     4    110,460,482     C
ESR1                    rs13192976     6    151,991,280     A

FAF1                    rs147696085    1    50,556,195      G
FAM186B                  rs7977389    12    49,587,939      T
FAM208A                  rs9827472     3    56,692,618      T

FBLN5                    rs2244643    14    91,892,678      A
FBN2                     rs6595838     5    128,532,506     A

FBXL19                  rs72799341    16    30,925,422      A

FER1L5                   rs7599598     2    96,686,103      A
FERMT2                   rs9888615    14    52,910,822      T

FGD5                    rs11128722     3    14,916,619      A
FGF5                    rs16998073     4    80,263,187      T
FGGY-HSD52               rs3889199     1    59,188,070      A

FIGN-PRPS1P1            rs16849211     2    164,043,173     T
FIGN-PRPS1P1             rs1446468     2    164,106,976     C
FIGN-GRB14              rs16849225     2    164,050,310     C

FLJ32810-TMEM133         rs633185     11    100,722,807     G
FN1                      rs1250259     2    215,435,759     A

FNDC1                    rs449789      6    159,278,093     C

FOSL2                     rs7562       2    28,412,873      T
FRMD3                   rs115795127    9    83,378,986      T
FURIN-FES                rs2521501    15    90,894,158      T
GATA2                   rs62270945     3    128,483,046     T

GJA1                    rs11154027     6    121,460,244     T
GNAS-EDN3                rs6015450    20    59,176,062      G
GOSR2                   rs17608766    17    46,935,905      T
GPAT2-FAHD2CP            rs2579519     2    96,009,418      T
GPATCH2                 rs12408022     1    217,545,447     T

GPR20                   rs34591516     8    141,356,987     T
GPR20                   rs78192203     8    141,364,973     T
GPR98/ARRDC3            rs10474346     5    91,268,322      C
GTF2B                   rs10922502     1    88,894,475      A

GUCY1A3                 rs13143871     4    155,698,052     T
GUCY1A3-GUCY1B3         rs13139571     4    155,724,361     C
GYPA_HHIP                rs4292285     4    144,350,802     T
HAAO-RNU6-242P-         rs13403122     2    42,851,618      C
AC016735.1
HDAC9                    rs2107595     7    19,009,765      A
HFE                      rs1799945     6    26,090,951      G
HFE                      rs1800562     6    26,092,913      A
HIPK2                    rs1011018     7    139,763,465     A
HIVEP3                   rs7515635     1    41,942,399      T
HM13-ID1                 rs6060114    20    31,581,870      T
HNF4G-RNU2-54P           rs1449544     8    75,679,645      A
HOTTIP                   rs1859168     7    27,202,740      C
HOXA3                    rs6969780     7    27,119,517      C
HOXA-EVX1               rs17428471     7    27,298,248      T
HOXB7                    rs7406910    17    48,610,894      T
HRCT1                   rs76452347     9    35,906,474      T
HSD52-LOC105378756      rs10889130     1    59,148,708      A
HSPB7                    rs1048238     1    16,015,154      T
IGFBP3                  rs11977526     7    45,968,511      A

INPP5B                   rs871524      1    37,945,773      A
INSR                     rs7248104    19     7,224,420      A
INSR                    rs36047283    19     7,255,690      G
ITGA11                   rs1563894    15    68,343,437      A
JAG1                     rs1327235    20    10,988,382      G
JAG1-LOC101929395        rs6040076    20    10,678,234      C
KCNH4-HSD17B1           rs79089478    17    42,165,223      T
KCNK3                    rs1275988     2    26,691,496      T
KIAA0753                 rs7226020    17     6,570,508      T

KIAA1462                 rs9337951    10    30,028,144      A

L3MBTL4                  rs403814     18     6,282,594      A
LHFPL2                  rs10057188     5    78,541,966      A

LINC01615-THBS2          rs1322639     6    169,187,008     A

LMO1                     rs110419     11     8,231,306      A
LOC101928278            rs10932679     2    216,787,868     T
LOC102723446            rs10260816     7    45,970,501      G
LOC105369687-           rs73075659    12    20,220,607      G
LOC105369688
LOC105370003            rs11067763    12    115,760,536     A
LOC105371811-           rs79917357    17    48,747,312      A
LOC105371812
LOC105374567-           rs72876037     2    42,967,456      T
LOC102723854
LOC105379231             rs9693857     8     9,409,607      T
LOC107986913-            rs7826238     8     8,529,585      T
LOC105379224
LOC283335               rs73099903    12    53,046,995      T
LRP12/ZFPM2             rs35783704     8    104,954,030     A
LRRC10B-SYT7             rs751984     11    61,510,774      T

LSP1-TNNT3               rs661348     11     1,884,062      T
MAP4                     rs319690      3    47,885,994      T
MAPK4-MRO               rs36010659    18    50,757,579      T

MCF2L                    rs9549328    13    112,981,842     T

MECOM                    rs419076      3    169,383,098     T
METTL21A-AC079767.3     rs55780018     2    207,661,416     T

MIR1263                 rs16833934     3    164,019,462     G
MKLN1                   rs13238550     7    131,374,297     A
MOV10                   rs12129649     1    112,688,881     T
MRAS                     rs2306374     3    138,401,110     T

MRC2                     rs740698     17    62,689,790      T
MSRA                    rs11249992     8    10,362,902      A
MTAP                     rs4364717     9    21,801,531      A
MTF1-SF3A3               rs4360494     1    37,990,219      C

MTHFR                   rs17367504     1    11,802,721      G
MTHFR-NPPB               rs4846049     1    11,790,308      T
MYEOV                   rs67330701    11    69,312,240      T

MYH6                     rs452036     14    23,396,676      A

NADK-CPSF3L             rs139385870    1     1,754,504      D

NFKBIA                    rs8904      14    35,402,011      A
NME7                     rs7519279     1    169,238,123     G
NOS3                     rs3918226     7    150,993,088     T
NOTCH3                  rs10418305    19    15,167,997      C
NOV                      rs2071518     8    119,423,572     T
NOX4                     rs2289125    11    89,491,285      A

NPNT                    rs13112725     4    105,990,585     C

NPPA-AS1, NPPA          rs12744757     1    11,846,764      T
NPR1                    rs35479618     1    153,689,947     A
NPR3-C5orf23             rs1173771     5    32,814,922      C

OBFC1                    rs4387287    10    103,918,139     A
OR5B12                  rs11229457    11    58,439,730      T
OSR1                     rs1344653     2    19,531,084      A
PABPC4                   rs4660293     1    39,562,508      G
PALLD-chr4mb174          rs1566497     4    168,795,997     A

PAPPA2                  rs61823001     1    176,664,440     G
PAX2                    rs112184198   10    100,844,757     A

PDE10A                  rs147212971    6    165,764,963     T

PDE3A                   rs12579720    12    20,020,830      C
PDE5A                   rs66887589     4    119,588,124     T

PHACTR1                  rs9349379     6    12,903,725      A
PHIP                    rs10943605     6    78,945,760      A
PIK3CG                  rs17477177     7    106,771,412     T
PKHD1                   rs13205180     6    51,967,696      T

PKN2-AS1                rs61767086     1    88,600,899      G
PLCB1                    rs6108168    20     8,645,624      A
PLCD3                   rs12946454    17    45,130,754      T
PLCE1                    rs932764     10    94,136,183      G
PLCE1                    rs932764     10    94,136,183      G
PLEKHA7                  rs177542     11    16,901,107      A
PLEKHA7-NUCB2            rs381815     11    16,880,721      T
PLEKHG1                 rs17080102     6    150,683,634     C
PNPT1                    rs1975487     2    55,581,918      A
POC5-SV2C               rs10078021     5    75,742,606      T

PPL                     rs12921187    16     4,893,018      T

PPP2R5E                  rs8016306    14    63,461,828      A
PRDM11                  rs11442819    11    45,186,590      I

PRDM16                   rs2493292     1     3,412,095      T
PRDM6-SUMO1P5            rs337100      5    123,210,816     A
PRDM6-CSNK1G3           rs13359291     5    123,140,763     A
PRDM8-FGF5               rs1902859     4    80,236,549      C
PRDM8-FGF5               rs1458038     4    80,243,569      T
PREX1                    rs6095241    20    48,692,260      A
PRKAG1                   rs1126930    12    49,005,349      C
PRKCE                   rs11690961     2    46,136,197      A

PRKD3                   rs13420463     2    37,290,423      A

PROCR                    rs867186     20    35,176,751      A
PRRC2A-BAG6             rs151168737    6    31,638,615      A
PSMD5                   rs10760117     9    120,824,459     T

PYY                     rs62080325    17    43,983,263      A
RABGAP1                 rs10818775     9    122,993,292     C
RAPSN, PSMC3,            rs7103648    11    47,440,232      A
SLC39A13
RBM47                   rs35529250     4    40,426,074      T
RCOR2                    rs4980532    11    63,913,247      T
RGL3                     rs167479     19    11,416,089      T

RNF207                   rs709209      1     6,218,354      A
RP11-273G15.2           rs62524579     8    142,979,538     A

RP11-321F6.1             rs7178615    15    66,576,734      A
RP11-435J9.2-TLN2        rs956006     15    62,516,340      C
RP11-439C8.2            rs143112823    3    154,990,178     A

RP11-61O1.1              rs9323988    14    98,121,293      T

RP4-710M16.1-PPAP2B-    rs112557609    1    56,111,252      A
PLPP3
RPL34P18-CDH17           rs7006531     8    94,098,516      G
RPL35P4-LOC107986733    rs10279895     7    27,288,591      G
RPL35P4-LOC107986733    rs11563582     7    27,312,031      A
RPL6-PTPN11-ALDH2       rs11066280    12    112,379,979     T
RPS29P9-LOC102724714     rs3845811     2    207,656,788     G
RRAS                    rs61760904    19    49,636,675      T
RSPO3                   rs13209747     6    126,794,309     T
RYK                      rs9859176     3    134,281,183     T

SBNO1                    rs1060105    12    123,321,672     T
SCAI-PPP6C              rs72765298     9    125,138,717     T

SDCCAG8                  rs953492      1    243,307,890     A

SENP2                   rs12374077     3    185,599,886     C

SEPT9                   rs57927100    17    77,321,218      G
SETBP1                  rs12958173    18    44,562,012      A
SH2B3                    rs3184504    12    111,446,804     T

SLC12A9                  rs7801190     7    100,860,471     C
SLC14A2                  rs7236548    18    45,517,785      A

SLC20A2                  rs2978456     8    42,467,247      T

SLC24A3                  rs6081613    20    19,485,263      A

SLC35F1                  rs9372498     6    118,251,323     A

SLC39A8                 rs13107325     4    102,267,552     T
SLC4A7                  rs11716531     3    27,415,717      A
SLC4A7                  rs13082711     3    27,496,418      T
SLC8A1                   rs4952611     2    40,340,603      T
SMARCA2-VLDLR            rs872256      9     2,496,480      T
SNORD32B                 rs926552      6    29,580,312      T
SNX31                    rs2978098     8    100,664,447     A
SOX6                     rs4757391    11    16,281,393      C
SSPN                     rs6487543    12    26,285,256      A
ST7L-CAPZA1-MOV10        rs2932538     1    112,673,921     G
STK39                    rs6749447     2    168,184,876     G
SUGCT                   rs76206723     7    40,408,372      A

SULT1C3                  rs6722745     2    108,258,788     C
SVEP1                   rs111245230    9    110,407,495     C
SWAP70                   rs2649044    11     9,742,422      T
TBC1D1-FLJ13197          rs2291435     4    38,385,774      T
TBX5-TBX3                rs2384550    12    114,914,926     A

TCF7L1                  rs11689667     2    85,264,242      T

TCF7L2                  rs34872471    10    112,994,312     T
TEX41                    rs1438896     2    144,888,505     T

TEX41                   rs55944332     2    144,969,054     G
TFAP2D                  rs78648104     6    50,715,296      T
TM6SF1                   rs2034618    15    83,130,880      C
TMEM161B                rs10059921     5    88,218,698      T

TMEM194B-NEMP2-NAB1      rs7592578     2    190,574,865     T

TNRC6A                  rs11639856    16    24,777,324      A
TNRC6B                   rs470113     22    40,333,610      A
TNS1                     rs1063281     2    217,804,009     T

TNXB                     rs2021783     6    32,077,074      C
TNXB                     rs185819      6    32,082,290      C
TP53-SLC2A4             rs78378222    17     7,668,434      T

TRAPPC9                  rs4288356     8    140,045,627     A
TRAPPC9                  rs4454254     8    140,049,929     A
TRIM36                  rs10077885     5    115,054,424     A
UBA52P4-LOC105377005     rs820430      3    27,507,409      A
ULK4                     rs7651190     3    41,724,463      G
ULK4                     rs9815354     3    41,912,651      A
ULK4                     rs7372217     3    41,948,630      G
UMOD                    rs13333226    16    20,354,332      NA
VAC14                   rs117006983   16    70,721,707      A
WNT3A                    rs2760061     1    228,003,374     A

XKR6                    rs10107145     8    10,900,703      G
XRCC6                   rs73161324    22    41,642,782      T
ZBTB38                  rs16851397     3    141,415,976     A
ZC3HC1                  rs11556924     7    130,023,656     T
ZFAT                     rs894344      8    134,600,502     A
ZNF101                   rs2304130    19    19,678,719      A
ZNF318-ABCC10           rs10948071     6    43,312,975      T
ZNF385B                 rs13407401     2    179,850,979     A
ZNF638                   rs3771371     2    71,400,409      T

ZNF652                  rs12940887    17    49,325,445      T
ZNF652                  rs16948048    17    49,363,104      G
ZNRF3                    rs4823006    22    29,055,683      G

Locus name              Best    Effect size of best   Coded allele
                        trait     trait (OR beta)      frequency

2q36.3                   DBP           0.17               0.19
7q32.1                   SBP          -0.224              0.29
ABHD17C                  SBP           0.322              0.18

ABHD17C                  SBP           0.316             0.461
ABLIM3-SH3TC2            DBP           0.26               0.16
ACE                      DBP           0.213              0.24

ACOX1                    SBP          -0.307              0.18

ADAMTS7-MORF4L1          DBP          -0.238              0.34

ADAMTS7-MORF4L1          PP            -0.28              0.14
ADAMTS8                  PP            0.337              0.21
ADAMTS9                  DBP          -0.204              0.35
ADCY3                    DBP           0.285              0.1
ADM                      SBP           0.413              0.44
ADM                      SBP          -0.619             0.058
ADM                      DBP          -0.299             0.058
ADO                      DPB           -0.20              0.38

ADRB1                    PP           -0.338              0.28
ADRB1-RNU6-709P          SBP           0.442             0.616
AGT                      SBP           0.42               0.41
AKT2                     DBP           0.252              0.44
AMH-SF3A2                PP            -0.55              0.21
ARHGAP12                 PP           -0.212              0.3

ARHGAP24                 SBP           0.62               0.19
ARNTL                    DBP           -0.25              0.43
ARVCF                    PP            0.24               0.27

ARVCF                    PP            0.261              0.29
ATP2B1                   DBP            0.5               0.83
ATP2B1                   SBP           1.26               0.21
ATP2B1                   BP             0.8               0.35
BAT2-BAT5                SBP           0.376              0.44
BDNF                     DBP          -0.163              0.26

BLK-GATA4                SBP            NA                0.38
C10orf107                DBP           0.436              0.16
C10orf107                DBP           0.19               0.15
C10orf32,                SBP           1.24               0.71
C10orf32-ASMT
C17orf82-TBX2            MAP           0.35               0.35
C20orf187                SBP           0.78               0.53
C2orf43                  PP           -0.223              0.31

C5orf56                  DBP           -0.2               0.14

CACNA1D                  DBP           0.39               0.39
CACNA2D2                 DBP           0.245              0.36

CACNB2                   DBP           0.332              0.34
CACNB2                   DBP           0.46               0.21
CAMKV-ACTBP13            DBP          -0.202              0.11

CAPZA1                   SBP           0.96               0.82
CASC15                   SBP           0.296              0.30

CASZ1                    SBP          -0.475              0.39
CCDC141                  DBP          -0.311              0.03

CCDC41-CEP83-            PP           -0.363              0.04
RN7SL483P
CCNE1                    DBP           0.177              0.19

CD34                     PP           -0.249              0.08
CDC42BPA                 DBP          -0.177              0.27
CDH13                    PP            0.329              0.17

CDH17                    SBP           -0.63              0.22
CELA2A                   SBP           0.412              0.19

CELA2A                   SBP           0.425              0.19
CEP164                   PP            0.236              0.47

CEP68                    PP            0.23               0.46

CERS5                    DBP           0.249              0.30

CFDP1                    SBP          -0.339              0.47

CHIC2                    PP            0.429              0.21
chr15mb95                DBP          -0.221              0.42

chr1mb25                 DBP           0.185              0.37
chr1mb9                  PP           -0.207              0.41

CHST12-LFNG              DBP          -0.205              0.21
CMIP                     DBP          -0.170              0.45
CNNM2                    SBP           1.082              0.09
COL21A1                  PP            -0.21              0.44
CPEB4                    DBP          -0.209              0.11

CRACR2B                  PP            0.222             <0.01
CRK                      SBP          -0.269              0.37

CRYAA-SIK1-RRP1B         SBP           0.503              0.19

CSK                      DBP           0.371              0.65
CYB561-LOC342541         DBP           0.198              0.61
CYP17A1-NT5C2            SBP            1.2               0.16

CYP1A1-ULK3              DBP           0.45               0.29

CYP2C19                  DPB           0.21               0.22
DBH                      DBP          -0.423              0.04
DNM3                     DBP          -0.165              0.47

DPEP1                    DBP           0.275              0.26

EBF1                     DBP          -0.281              0.18
EBF2                     SBP          -0.411              0.33
ENPEP                    DBP           0.39               0.42
ESR1                     PP           -0.332              0.21

FAF1                     PP            0.298              0.06
FAM186B                  PP            0.237              0.18
FAM208A                  DBP          -0.177              0.46

FBLN5                    PP           -0.213              0.29
FBN2                     SBP           0.344              0.41

FBXL19                   DBP           0.185              0.27

FER1L5                   DBP           -0.31              0.42
FERMT2                   SBP          -0.318              0.36

FGD5                     SBP          -0.383              0.41
FGF5                     DBP           0.21               0.23
FGGY-HSD52               PP            0.351              0.14

FIGN-PRPS1P1             PP            0.364              0.23
FIGN-PRPS1P1             SBP           0.538              0.55
FIGN-GRB14               SBP           0.75               0.23

FLJ32810-TMEM133         SBP          -0.565              0.36
FN1                      PP           -0.314              0.23

FNDC1                    PP            0.359              0.15

FOSL2                    SBP           0.263              0.50
FRMD3                    BP             NA                 NR
FURIN-FES                SBP           0.65               0.21
GATA2                    PP            0.607              0.01

GJA1                     PP            0.207              0.38
GNAS-EDN3                SBP           0.896              0.10
GOSR2                    SBP          -0.556              0.05
GPAT2-FAHD2CP            DBP          -0.197              0.41
GPATCH2                  DBP           0.198              0.26

GPR20                    SBP           0.323              0.05
GPR20                    BP             NA                 NR
GPR98/ARRDC3             DBP            1.1               0.31
GTF2B                    SBP          -0.382              0.34

GUCY1A3                  SBP           0.96               0.80
GUCY1A3-GUCY1B3          DBP           0.26               0.21
GYPA_HHIP                DBP           0.177              0.41
HAAO-RNU6-242P-          DBP           0.226              0.20
AC016735.1
HDAC9                    PP            0.31               0.25
HFE                      DBP           0.457              0.09
HFE                      DBP           0.394              0.06
HIPK2                    SBP          -0.329              0.35
HIVEP3                   SBP           0.336              0.47
HM13-ID1                 DBP           0.267              0.27
HNF4G-RNU2-54P           PP            0.183              0.41
HOTTIP                   DBP           0.436              0.92
HOXA3                    BP             NA                 NR
HOXA-EVX1                SBP            1.2               0.08
HOXB7                    SBP          -0.456              0.12
HRCT1                    DBP           -0.25              0.15
HSD52-LOC105378756       PP            0.288              0.33
HSPB7                    SBP           0.366              0.02
IGFBP3                   DBP            0.3               0.44

INPP5B                   PP            0.228              0.33
INSR                     PP            -0.20              0.35
INSR                     SBP           0.801              0.11
ITGA11                   SBP          -0.093              0.18
JAG1                     DBP           0.302              0.46
JAG1-LOC101929395        PP            0.285              0.49
KCNH4-HSD17B1            PP            0.584              0.01
KCNK3                    SBP           -0.6               0.41
KIAA0753                 PP           -0.256              0.38

KIAA1462                 PP            0.28               0.26

L3MBTL4                  BP            1.15                NR
LHFPL2                   PP           -0.205              0.24

LINC01615-THBS2          PP            0.316              0.33

LMO1                     DBP           0.159              0.43
LOC101928278             PP            0.226              0.19
LOC102723446             PP            0.298              0.43
LOC105369687-            SBP           0.357              0.31
LOC105369688
LOC105370003             DBP           0.51               0.62
LOC105371811-            SBP           0.342              0.17
LOC105371812
LOC105374567-            SBP           0.534              0.12
LOC102723854
LOC105379231             SBP           0.337              0.45
LOC107986913-            SBP           0.335              0.47
LOC105379224
LOC283335                SBP           0.768              0.06
LRP12/ZFPM2              SBP          -0.609              0.03
LRRC10B-SYT7             MAP           0.33               0.27

LSP1-TNNT3               MAP           -0.65              0.42
MAP4                     DBP           0.282              0.41
MAPK4-MRO                PP            0.25               0.12

MCF2L                    SBP           0.318              0.22

MECOM                    SBP           0.409              0.42
METTL21A-AC079767.3      SBP          -0.391              0.35

MIR1263                  DBP           -1.63              0.31
MKLN1                    SBP           0.331              0.33
MOV10                    DBP           0.548              0.06
MRAS                     DBP          -0.184              0.08

MRC2                     PP           -0.228              0.41
MSRA                     SBP           0.293              0.38
MTAP                     DBP          -0.175              0.43
MTF1-SF3A3               PP            0.278              0.38

MTHFR                    DBP           0.526              0.15
MTHFR-NPPB               DBP           -0.55              0.37
MYEOV                    DBP          -0.367              0.12

MYH6                     PP           -0.282              0.34

NADK-CPSF3L              SBP          -0.352              0.33

NFKBIA                   SBP           0.377              0.40
NME7                     PP            0.218              0.13
NOS3                     DBP           0.83               0.03
NOTCH3                   PP           -0.282              0.13
NOV                      PP            0.312              0.32
NOX4                     PP           -0.377              0.32

NPNT                     SBP           0.435              0.34

NPPA-AS1, NPPA           SBP           0.695              0.06
NPR1                     SBP           1.34               0.01
NPR3-C5orf23             SBP           0.63               0.34

OBFC1                    SBP           0.338              0.32
OR5B12                   SBP          -0.312              0.22
OSR1                     PP            -0.27              0.38
PABPC4                   DBP           0.27               0.10
PALLD-chr4mb174          PP            0.236              0.23

PAPPA2                   PP            0.31               0.03
PAX2                     SBP          -0.659              0.05

PDE10A                   DBP          -0.360              0.13

PDE3A                    DBP           -0.32              0.46
PDE5A                    DBP          -0.215              0.50

PHACTR1                  SBP           0.289              0.38
PHIP                     DBP           0.18               0.49
PIK3CG                   PP           -0.418              0.17
PKHD1                    DBP           0.168              0.34

PKN2-AS1                 PP            0.413              0.14
PLCB1                    DBP          -0.211              0.38
PLCD3                    SBP           0.28               0.21
PLCE1                    SBP           0.484              0.43
PLCE1                    SBP           0.484              0.44
PLEKHA7                  DBP           0.243              0.50
PLEKHA7-NUCB2            SBP           0.84               0.21
PLEKHG1                  DBP           -0.74              0.12
PNPT1                    DBP          -0.217              0.32
POC5-SV2C                DBP          -0.164              0.46

PPL                      DBP          -0.174              0.41

PPP2R5E                  SBP           0.335              0.41
PRDM11                   PP           -0.279              0.13

PRDM16                   SBP           0.42               0.13
PRDM6-SUMO1P5            PP            0.277              0.40
PRDM6-CSNK1G3            SBP           0.53               0.28
PRDM8-FGF5               SBP           1.34               0.41
PRDM8-FGF5               DBP           0.403              0.30
PREX1                    DBP          -0.168              0.46
PRKAG1                   PP             0.5               0.02
PRKCE                    PP            0.34               0.04

PRKD3                    SBP           0.356              0.49

PROCR                    DBP           0.265              0.11
PRRC2A-BAG6              DBP           0.249              0.46
PSMD5                    SBP           0.334              0.42

PYY                      PP           -0.186              0.21
RABGAP1                  PP            0.254              0.30
RAPSN, PSMC3,            DBP          -0.203              0.33
SLC39A13
RBM47                    SBP          -1.537             <0.01
RCOR2                    PP            0.301              0.56
RGL3                     DBP           -0.33              0.49

RNF207                   PP            0.199              0.36
RP11-273G15.2            DBP          -0.175              0.48

RP11-321F6.1             DBP          -0.179              0.36
RP11-435J9.2-TLN2        PP            0.188              0.23
RP11-439C8.2             DBP          -0.403              0.06

RP11-61O1.1              PP           -0.212              0.29

RP4-710M16.1-PPAP2B-     PP            0.227              0.22
PLPP3
RPL34P18-CDH17           BP             NA                 NR
RPL35P4-LOC107986733     DBP          0.7553               NR
RPL35P4-LOC107986733     BP             NA                 NR
RPL6-PTPN11-ALDH2        DBP           1.01               0.04
RPS29P9-LOC102724714     SBP           0.284              0.43
RRAS                     SBP           1.499             <0.01
RSPO3                    DBP           0.56               0.35
RYK                      SBP           0.322              0.25

SBNO1                    DBP          -0.182              0.18
SCAI-PPP6C               PP           -0.374              0.06

SDCCAG8                  DBP           0.22               0.49

SENP2                    DBP           0.163              0.42

SEPT9                    SBP          -0.489              0.01
SETBP1                   SBP           0.386              0.25
SH2B3                    SBP           0.75               0.33

SLC12A9                  BP            1.31               0.72
SLC14A2                  PP            0.352              0.3

SLC20A2                  PP           -0.188              0.45

SLC24A3                  PP            0.263              0.31

SLC35F1                  DBP           0.334              0.07

SLC39A8                  DBP          -0.684               0
SLC4A7                   DBP           0.213             0.237
SLC4A7                   DBP          -0.238              0.12
SLC8A1                   DBP          -0.157              0.34
SMARCA2-VLDLR            SBP           0.096              0.43
SNORD32B                 DBP           -0.31              0.07
SNX31                    DBP           0.165              0.34
SOX6                     DBP           0.49               0.28
SSPN                     SBP            0.3               0.46
ST7L-CAPZA1-MOV10        DBP           0.24               0.17
STK39                    SBP             3                0.48
SUGCT                    PP           -0.346              0.18

SULT1C3                  SBP           0.28               0.4
SVEP1                    SBP           0.94               0.03
SWAP70                   DBP            0.2              0.547
TBC1D1-FLJ13197          SBP          -0.378              0.4
TBX5-TBX3                DBP           -0.35              0.29

TCF7L1                   PP            0.176              0.28

TCF7L2                   PP           -0.226              0.24
TEX41                    DBP           0.234              0.3

TEX41                    DBP           0.267              0.24
TFAP2D                   SBP          -0.481              0.09
TM6SF1                   DBP           0.21               0.22
TMEM161B                 SBP          -0.526              0.06

TMEM194B-NEMP2-NAB1      DBP          -0.240              0.18

TNRC6A                   SBP           -0.37              0.17
TNRC6B                   PP           -0.253              0.21
TNS1                     DBP          -0.200              0.43

TNXB                     DBP           0.49               0.79
TNXB                     SBP           0.365             0.513
TP53-SLC2A4              PP            0.904               0

TRAPPC9                  PP            0.224             0.615
TRAPPC9                  PP           -0.261              0.45
TRIM36                   DBP          -0.194              0.42
UBA52P4-LOC105377005     SBP           0.76               0.32
ULK4                     BP             NA                 NR
ULK4                     DBP            0.6               0.17
ULK4                     BP             NA                 NR
UMOD                     HTN            NA                0.24
VAC14                    PP            0.986               0
WNT3A                    DBP           0.23               0.35

XKR6                     SBP           0.361             0.528
XRCC6                    PP            0.496              0.02
ZBTB38                   DBP          -0.493              0.05
ZC3HC1                   DBP          -0.214              0.27
ZFAT                     SBP          -0.258              0.47
ZNF101                   DBP          -0.292              0.11
ZNF318-ABCC10            PP            -0.38              0.43
ZNF385B                  SBP           0.434             0.291
ZNF638                   PP           -0.160              0.37

ZNF652                   DBP           0.26              0.374
ZNF652                   DBP           0.39               0.29
ZNRF3                    SBP           -0.33              0.45

Locus name                 Reporting article

2q36.3                   Surendran et al. [29]
7q32.1                   Surendran et al. [29]
ABHD17C                   Hoffmann et al. [8],
                           Warren et al. [26]
ABHD17C                     Wain et al. [27]
ABLIM3-SH3TC2               Kato et al. [20]
ACE                       Hoffmann et al. [8],
                           Warren et al. [26]
ACOX1                     Hoffmann et al. [8],
                           Warren et al. [26]
ADAMTS7-MORF4L1           Hoffmann et al. [8],
                           Warren et al. [26]
ADAMTS7-MORF4L1           Hoffmann et al. [8]
ADAMTS8                     Wain et al. [19]
ADAMTS9                    Ehret et al. [12]
ADCY3                      Warren et al. [26]
ADM                        Ehret et al. [12]
ADM                        Ehret et al. [18]
ADM                        Ehret et al. [18]
ADO                          Liuetal. [23],
                         Surendran et al. [29]
ADRB1                       Wain et al. [19]
ADRB1-RNU6-709P             Wain et al. [27]
AGT                       Johnson et al. [30]
AKT2                        Wain et al. [27]
AMH-SF3A2                   Kato et al. [20]
ARHGAP12                  Hoffmann et al. [8],
                           Warren et al. [26]
ARHGAP24                    Kato et al. [20]
ARNTL                       Liu et al. [23]
ARVCF                     Hoffmann et al. [8],
                           Warren et al. [26]
ARVCF                       Wain et al. [27]
ATP2B1                      Levy et al. [9]
ATP2B1                      Levy et al. [9]
ATP2B1                     Kelly et al. [31]
BAT2-BAT5                 Johnson et al. [30]
BDNF                      Hoffmann et al. [8],
                           Warren et al. [26]
BLK-GATA4                    Ho et al. [33]
C10orf107                   Wain et al. [27]
C10orf107               Newton-Cheh et al. [10]
C10orf32,                    Lu et al. [51]
C10orf32-ASMT
C17orf82-TBX2               Kato et al. [20]
C20orf187                    Lu et al. [51]
C2orf43                   Hoffmann et al. [8],
                           Warren et al. [26]
C5orf56                     Liu et al. [23],
                         Surendran et al. [29]
CACNA1D                      Lu et al. [51]
CACNA2D2                  Hoffmann et al. [8],
                           Warren et al. [26]
CACNB2                      Wain et al. [27]
CACNB2                      Levy et al. [9]
CAMKV-ACTBP13             Hoffmann et al. [8],
                           Warren et al. [26]
CAPZA1                       Lu et al. [51]
CASC15                    Hoffmann et al. [8],
                           Warren et al. [26]
CASZ1                      Ehret et al. [12]
CCDC141                   Hoffmann et al. [8],
                           Warren et al. [26]
CCDC41-CEP83-             Hoffmann et al. [8],
RN7SL483P                  Warren et al. [26]
CCNE1                     Hoffmann et al. [8],
                           Warren et al. [26]
CD34                       Warren et al. [26]
CDC42BPA                   Warren et al. [26]
CDH13                     Hoffmann et al. [8],
                           Warren et al. [26]
CDH17                       Zhu et al. [32]
CELA2A                    Hoffmann et al. [8],
                           Warren et al. [26]
CELA2A                      Wain et al. [27]
CEP164                    Hoffmann et al. [8],
                           Warren et al. [26]
CEP68                     Hoffmann et al. [8],
                           Warren et al. [26]
CERS5                       Liu et al. [23],
                         Surendran et al. [29]
CFDP1                     Hoffmann et al. [8],
                           Warren et al. [26]
CHIC2                       Wain et al. [19]
chr15mb95                 Hoffmann et al. [8],
                           Warren et al. [26]
chr1mb25                   Warren et al. [26]
chr1mb9                   Hoffmann et al. [8],
                           Warren et al. [26]
CHST12-LFNG                Ehret et al. [12]
CMIP                       Warren et al. [26]
CNNM2                       Wain et al. [27]
COL21A1                     Liu et al. [23]
CPEB4                     Hoffmann et al. [8],
                           Warren et al. [26]
CRACR2B                    Warren et al. [26]
CRK                       Hoffmann et al. [8],
                           Warren et al. [26]
CRYAA-SIK1-RRP1B           Ehret et al. [12],
                         Surendran et al. [29]
CSK                         Wain et al. [27]
CYB561-LOC342541            Wain et al. [27]
CYP17A1-NT5C2               Levy et al. [9],
                        Newton-Cheh et al. [10]
CYP1A1-ULK3                 Levy et al. [9],
                        Newton-Cheh et al. [10]
CYP2C19                     Liu et al. [23]
DBH                        Ehret et al. [12]
DNM3                      Hoffmann et al. [8],
                           Warren et al. [26]
DPEP1                       Liu et al. [23],
                         Surendran et al. [29]
EBF1                      Johnson et al. [30]
EBF2                        Wain et al. [27]
ENPEP                       Kato et al. [22]
ESR1                      Hoffmann et al. [8],
                           Warren et al. [26]
FAF1                      Hoffmann et al. [8]
FAM186B                   Hoffmann et al. [8]
FAM208A                   Hoffmann et al. [8],
                           Warren et al. [26]
FBLN5                     Hoffmann et al. [8]
FBN2                      Hoffmann et al. [8],
                           Warren et al. [26]
FBXL19                    Hoffmann et al. [8],
                           Warren et al. [26]
FER1L5                     Ganesh et al. [34]
FERMT2                    Hoffmann et al. [8],
                           Warren et al. [26]
FGD5                       Ehret et al. [12]
FGF5                    Newton-Cheh et al. [10]
FGGY-HSD52                Hoffmann et al. [8],
                           Warren et al. [26]
FIGN-PRPS1P1                Wain et al. [27]
FIGN-PRPS1P1                Wain et al. [27]
FIGN-GRB14                 Ehret et al. [18],
                           Kato et al. [22],
                            Wain et al. [19]
FLJ32810-TMEM133          Johnson et al. [30]
FN1                       Hoffmann et al. [8],
                           Warren et al. [26]
FNDC1                     Hoffmann et al. [8],
                           Warren et al. [26]
FOSL2                      Warren et al. [26]
FRMD3                      Liang et al. [35]
FURIN-FES                 Johnson et al. [30]
GATA2                     Hoffmann et al. [8],
                           Warren et al. [26]
GJA1                       Warren et al. [26]
GNAS-EDN3                 Johnson et al. [30]
GOSR2                     Johnson et al. [30]
GPAT2-FAHD2CP              Warren et al. [26]
GPATCH2                   Hoffmann et al. [8],
                           Warren et al. [26]
GPR20                    Surendran et al. [29]
GPR20                      Liang et al. [35]
GPR98/ARRDC3                Fox et al. [36]
GTF2B                     Hoffmann et al. [8],
                           Warren et al. [26]
GUCY1A3                      Lu et al. [51]
GUCY1A3-GUCY1B3           Johnson et al. [30]
GYPA_HHIP                 Hoffmann et al. [8]
HAAO-RNU6-242P-           Hoffmann et al. [8],
AC016735.1                 Warren et al. [26]
HDAC9                       Kato et al. [20]
HFE                       Johnson et al. [30]
HFE                         Wain et al. [27]
HIPK2                      Warren et al. [26]
HIVEP3                     Ehret et al. [12]
HM13-ID1                  Hoffmann et al. [8]
HNF4G-RNU2-54P            Hoffmann et al. [8]
HOTTIP                      Wain et al. [27]
HOXA3                      Liang et al. [35]
HOXA-EVX1               Franceschini et al. [24]
HOXB7                    Surendran et al. [29]
HRCT1                       Liu et al. [23]
HSD52-LOC105378756          Wain et al. [27]
HSPB7                       Wain et al. [27]
IGFBP3                      Zhu et al. [32],
                            Liu et al. [23]
INPP5B                      Wain et al. [27]
INSR                        Liu et al. [23]
INSR                        Wain et al. [27]
ITGA11                     Parmar et al. [37]
JAG1                      Johnson et al. [30]
JAG1-LOC101929395           Wain et al. [27]
KCNH4-HSD17B1              Warren et al. [26]
KCNK3                      Ganesh et al. [34]
KIAA0753                  Hoffmann et al. [8],
                           Warren et al. [26]
KIAA1462                  Hoffmann et al. [8],
                           Warren et al. [26]
L3MBTL4                     Liu et al. [23]
LHFPL2                    Hoffmann et al. [8],
                           Warren et al. [26]
LINC01615-THBS2           Hoffmann et al. [8],
                           Warren et al. [26]
LMO1                     Surendran et al. [29]
LOC101928278                Wain et al. [27]
LOC102723446                Wain et al. [27]
LOC105369687-               Wain et al. [27]
LOC105369688
LOC105370003                 Lu et al. [51]
LOC105371811-               Wain et al. [27]
LOC105371812
LOC105374567-               Wain et al. [27]
LOC102723854
LOC105379231                Wain et al. [27]
LOC107986913-               Wain et al. [27]
LOC105379224
LOC283335                   Wain et al. [27]
LRP12/ZFPM2                 Wain et al. [27]
LRRC10B-SYT7               Kato et al. [20],
                           Ehret et al. [12]
LSP1-TNNT3                Johnson et al. [30]
MAP4                        Wain et al. [19]
MAPK4-MRO                 Hoffmann et al. [8],
                           Warren et al. [26]
MCF2L                     Hoffmann et al. [8],
                           Warren et al. [26]
MECOM                     Johnson et al. [30]
METTL21A-AC079767.3       Hoffmann et al. [8],
                           Warren et al. [26]
MIR1263                    Simino et al. [38]
MKLN1                      Warren et al. [26]
MOV10                       Wain et al. [27]
MRAS                      Hoffmann et al. [8],
                           Warren et al. [26]
MRC2                       Warren et al. [26]
MSRA                        Wain et al. [27]
MTAP                       Warren et al. [26]
MTF1-SF3A3                Hoffmann et al. [8],
                           Warren et al. [26]
MTHFR                       Wain et al. [27]
MTHFR-NPPB                Johnson et al. [30]
MYEOV                     Hoffmann et al. [8],
                           Warren et al. [26]
MYH6                        Liu et al. [23],
                         Surendran et al. [29]
NADK-CPSF3L               Hoffmann et al. [8],
                           Warren et al. [26]
NFKBIA                      Wain et al. [27]
NME7                      Hoffmann et al. [8]
NOS3                      Johnson et al. [30]
NOTCH3                    Hoffmann et al. [8]
NOV                         Wain et al. [19]
NOX4                      Hoffmann et al. [8],
                           Warren et al. [26]
NPNT                      Hoffmann et al. [8],
                           Warren et al. [26]
NPPA-AS1, NPPA              Wain et al. [27]
NPR1                        Liu et al. [23]
NPR3-C5orf23              Johnson et al. [30],
                            Kato et al. [22]
OBFC1                    Surendran et al. [29]
OR5B12                   Surendran et al. [29]
OSR1                        Kato et al. [20]
PABPC4                      Liu et al. [23]
PALLD-chr4mb174           Hoffmann et al. [8],
                           Warren et al. [26]
PAPPA2                    Hoffmann et al. [8]
PAX2                      Hoffmann et al. [8],
                           Warren et al. [26]
PDE10A                    Hoffmann et al. [8],
                           Warren et al. [26]
PDE3A                       Kato et al. [20]
PDE5A                     Hoffmann et al. [8],
                           Warren et al. [26]
PHACTR1                  Surendran et al. [29]
PHIP                        Liu et al. [23]
PIK3CG                      Wain et al. [19]
PKHD1                     Hoffmann et al. [8],
                           Warren et al. [26]
PKN2-AS1                    Wain et al. [27]
PLCB1                      Warren et al. [26]
PLCD3                   Newton-Cheh et al. [10]
PLCE1                     Johnson et al. [30]
PLCE1                      Ehret et al. [18]
PLEKHA7                     Wain et al. [27]
PLEKHA7-NUCB2               Levy et al. [9]
PLEKHG1                 Franceschini et al. [24]
PNPT1                      Ehret et al. [12]
POC5-SV2C                 Hoffmann et al. [8],
                           Warren et al. [26]
PPL                       Hoffmann et al. [8],
                           Warren et al. [26]
PPP2R5E                    Warren et al. [26]
PRDM11                    Hoffmann et al. [8],
                           Warren et al. [26]
PRDM16                      Liu et al. [23]
PRDM6-SUMO1P5               Wain et al. [27]
PRDM6-CSNK1G3               Kato et al. [20]
PRDM8-FGF5                    Luetal. [51]
PRDM8-FGF5                  Wain et al. [27]
PREX1                    Surendran et al. [29]
PRKAG1                   Surendran et al. [29]
PRKCE                     Hoffmann et al. [8],
                           Warren et al. [26]
PRKD3                     Hoffmann et al. [8],
                           Warren et al. [26]
PROCR                    Surendran et al. [29]
PRRC2A-BAG6                 Wain et al. [27]
PSMD5                      Ehret et al. [12],
                            Liu et al. [23]
PYY                        Warren et al. [26]
RABGAP1                   Hoffmann et al. [8]
RAPSN, PSMC3,              Ehret et al. [12]
SLC39A13
RBM47                    Surendran et al. [29]
RCOR2                       Wain et al. [27]
RGL3                        Liu et al. [23],
                         Surendran et al. [29]
RNF207                   Surendran et al. [29]
RP11-273G15.2             Hoffmann et al. [8],
                           Warren et al. [26]
RP11-321F6.1               Warren et al. [26]
RP11-435J9.2-TLN2         Hoffmann et al. [8]
RP11-439C8.2              Hoffmann et al. [8],
                           Warren et al. [26]
RP11-61O1.1               Hoffmann et al. [8],
                           Warren et al. [26]
RP4-710M16.1-PPAP2B-      Hoffmann et al. [8],
PLPP3                      Warren et al. [26]
RPL34P18-CDH17             Liang et al. [35]
RPL35P4-LOC107986733       Liang et al. [35]
RPL35P4-LOC107986733       Liang et al. [35]
RPL6-PTPN11-ALDH2           Kato et al. [22]
RPS29P9-LOC102724714        Wain et al. [27]
RRAS                     Surendran et al. [29]
RSPO3                   Franceschini et al. [24]
RYK                       Hoffmann et al. [8],
                           Warren et al. [26]
SBNO1                    Surendran et al. [29]
SCAI-PPP6C                Hoffmann et al. [8],
                           Warren et al. [26]
SDCCAG8                   Hoffmann et al. [8],
                           Warren et al. [26]
SENP2                     Hoffmann et al. [8],
                           Warren et al. [26]
SEPT9                       Wain et al. [27]
SETBP1                     Ehret et al. [12]
SH2B3                       Levy et al. [9],
                        Newton-Cheh et al. [10]
SLC12A9                    Lettre et al. [39]
SLC14A2                   Hoffmann et al. [8],
                           Warren et al. [26]
SLC20A2                   Hoffmann et al. [8],
                           Warren et al. [26]
SLC24A3                   Hoffmann et al. [8],
                           Warren et al. [26]
SLC35F1                   Hoffmann et al. [8],
                           Warren et al. [26]
SLC39A8                   Johnson et al. [30]
SLC4A7                      Wain et al. [27]
SLC4A7                    Johnson et al. [30]
SLC8A1                     Warren et al. [26]
SMARCA2-VLDLR              Parmar et al. [37]
SNORD32B                    Liu et al. [23]
SNX31                      Warren et al. [26]
SOX6                          Luetal. [51]
SSPN                       Warren et al. [26]
ST7L-CAPZA1-MOV10         Johnson et al. [30]
STK39                       Wang et al. [40]
SUGCT                     Hoffmann et al. [8],
                           Warren et al. [26]
SULT1C3                     Liu et al. [23]
SVEP1                       Liu et al. [23]
SWAP70                      Wain et al. [27]
TBC1D1-FLJ13197            Ehret et al. [12]
TBX5-TBX3                   Levy et al. [9],
                            Kato et al. [22]
TCF7L1                    Hoffmann et al. [8],
                           Warren et al. [26]
TCF7L2                    Hoffmann et al. [8]
TEX41                     Hoffmann et al. [8],
                           Warren et al. [26]
TEX41                       Wain et al. [27]
TFAP2D                     Warren et al. [26]
TM6SF1                    Hoffmann et al. [8]
TMEM161B                  Hoffmann et al. [8],
                           Warren et al. [26]
TMEM194B-NEMP2-NAB1       Hoffmann et al. [8],
                           Warren et al. [26]
TNRC6A                      Liu et al. [23]
TNRC6B                   Surendran et al. [29]
TNS1                      Hoffmann et al. [8],
                           Warren et al. [26]
TNXB                         Lu et al. [51]
TNXB                        Wain et al. [27]
TP53-SLC2A4               Hoffmann et al. [8],
                           Warren et al. [26]
TRAPPC9                     Wain et al. [27]
TRAPPC9                    Warren et al. [26]
TRIM36                     Ehret et al. [12]
UBA52P4-LOC105377005          Luetal. [51]
ULK4                       Liang et al. [35]
ULK4                        Levy et al. [9]
ULK4                       Liang et al. [35]
UMOD                    Padmanabhan et al. [25]
VAC14                      Warren et al. [26]
WNT3A                     Hoffmann et al. [8],
                           Warren et al. [26]
XKR6                        Wain et al. [27]
XRCC6                      Warren et al. [26]
ZBTB38                   Surendran et al. [29]
ZC3HC1                     Ehret et al. [12]
ZFAT                       Warren et al. [26]
ZNF101                   Surendran et al. [29]
ZNF318-ABCC10              Ganesh et al. [34]
ZNF385B                     Wain et al. [27]
ZNF638                    Hoffmann et al. [8],
                           Warren et al. [26]
ZNF652                      Wain et al. [27]
ZNF652                  Newton-Cheh et al. [10]
ZNRF3                       Liu et al. [23]

SBP: systolic blood pressure; DBP: diastolic blood pressure; PP: pulse
pressure; MAP: mean arterial pressure; HTN: hypertension; NR: not
recorded; NA: not available.
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Author:Azam, Afifah Binti; Azizan, Elena Aisha Binti
Publication:International Journal of Endocrinology
Date:Jan 1, 2018
Words:11001
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