Abstract
Hypertension is a complex disease that is caused by the interaction of multiple genetic and environmental risk factors, affecting 30% adult in industrialized countries. The identification of genetic factors that impact one’s predisposition to hypertension and its progression is an ongoing challenge. A genome-wide association study of African-Americans, who have one of the highest rates of hypertension in the world, was reported. We replicated the GWAS results in 8842 unrelated Koreans. Fifteen of the 30 reported SNPs were analyzed for their association with blood pressure and hypertension. Linear regression was used to analyze blood pressure as a quantitative trait in 7551 subjects, and a case-control study was performed using 1968 hypertensive cases and 4452 normotensive controls by logistic regression analysis. The quantitative trait study demonstrated a moderate association of 2 SNPs, rs9301196 (p=4.9×10−3 for diastolic blood pressure) and rs2823756 (p=0.04 for systolic blood pressure), which were also associated with hypertension (p=0.042 and p=6.3×10−3, respectively). Further, 3 SNPs were associated with hypertension (p=0.042 for rs7902529, p=0.027 for rs10135446, and p=0.01 for rs4613079) but not with blood pressure. Based on the moderate association signals and the low proportion of positive signals, this cross validation between African-Americans and Asians suggests that association studies of blood pressure traits require a larger number of subjects and a more refined design.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adeyemo A, Gerry N, Chen G, Herbert A, Doumatey A, Huang H, Zhou J, Lashley K, Chen Y, Christman M et al. (2009) A genome-wide association study of hypertension and blood pressure in African Americans. PLoS Genet. 5(7): e1000564.
Anney RJ, Lasky-Su J, O’Dushlaine C, Kenny E, Neale BM, Mulligan A, Franke B, Zhou K, Chen W, Christiansen H, et al. (2008) Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. Am. J. Med. Genet. B. 147B: 1369–1378.
Cho YS, Go MJ, Kim YJ, Heo JY, Oh JH, Ban HJ, Yoon D, Lee MH, Kim DJ, Park M et al. (2009) A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat. Genet. 41(5): 527–534.
Dorus S, Gilbert SL, Forster ML, Barndt RJ and Lahn BT (2003) The CDY-related gene family: coordinated evolution in copy number, expression profile and protein sequence. Hum. Mol. Genet. 12(14): 1643–1650.
Ehret GB (2010) Genome-Wide Association Studies: Contribution of Genomics to Understanding Blood Pressure and Essential Hypertension. Curr. Hypertens. Rep. 12: 17–25.
Fields LE, Burt VL, Cutler JA, Hughes J, Roccella EJ, Sorlie P (2004) The burden of adult hypertension in the United States 1999 to 2000: a rising tide. Hypertension 44:398–404.
Heard-Costa NL, Zillikens MC, Monda KL, Johansson A, Harris TB, Fu M, Haritunians T, Feitosa MF, Aspelund T, Eiriksdottir G et al. (2009) NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium. PLoS Genet. 5(6): e1000539.
Hong KW, Jin HS, Cho YS, Lee JY, Lee JE, Cho NH, Shin C, Lee SH, Park HK and Oh B (2009) Replication of the Wellcome Trust genome-wide association study on essential hypertension in a Korean population. Hypertens. Res. 32(7): 570–574.
Joseph LI, Domenic AS and Henry RB (2008) Hypertension in Blacks. In Hypertension Primer, 4 ed. Lippincott williams & Wilkins, Philadelphia, pp. 297.
Lane DA and Lip GY (2001) Ethnic differences in hypertension and blood pressure control in the UK. QJM-An Int. J. Med. 94(7): 391–396.
Lawes CM, Vander Hoorn S, Rodgers A (2008) Global burden of blood-pressure-related disease, 2001. Lancet. 371:1513–1518.
Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, Glazer NL, Morrison AC, Johnson AD, Aspelund T, et al. (2009) Genome-wide association study of blood pressure and hypertension. Nat. Genet. 41:677–687.
Medical Research Council Working Party (1985) Intervention Trial Research Group. MRC trial of treatment of mild hypertension: principal results. Br. Med. J. 291: 97–104.
Multiple Risk Factor Intervention Trial Research Group (1982) Multiple risk factor intervention trial, risk factor changes and mortality results. JAMA-J. Am. Med. Assoc. 248: 1465–1467.
Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, et al. (2009) Genome-wide association study identifies eight loci associated with blood pressure. Nat. Genet. 41:666–676.
Oguri M, Kato K, Yokoi K, Yoshida T, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Nozawa Y, et al. (2010) Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals. Am. J. Hypertens. 23: 70–77.
Rabbee N and Speed TP (2006) A genotype calling algorithm for affymetrix SNP arrays. Bioinformatics 22: 7–12.
Rose JE, Behm FM, Drgon T, Johnson C and Uhl GR (2010) Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Mol. Med. 16: 247–253.
Wright S (1969) Evolution and the Genetics of Populations. Univ. of Chicago Press, Chicago.
WTCCC (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447: 661–678.
Zhang K, Weder AB, Eskin E and O’Connor DT (2010) Genome-wide case/control studies in hypertension: only the ‘tip of the iceberg’. J. Hypertens. 28: 1115–1123.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Jin, HS., Hong, KW., Lim, JE. et al. Replication of an African-American GWAS on blood pressure and hypertension in the Korean population. Genes Genom 33, 127–132 (2011). https://doi.org/10.1007/s13258-010-0138-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13258-010-0138-y