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Advances in genome-wide association studies on essential hypertension

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  • 1. School of Public Health, Xinjiang Medical University, Urumqi 830054, China 2. Department of Clinical Epidemiology, Children's Hospital of Fudan University, Shanghai 201102, China

Received date: 2011-12-13

  Revised date: 2012-02-17

  Online published: 2012-07-25

Abstract

Since the first genome-wide association study was reported in 2007, hypertension has attracted numerous studies to identify its genetic basis. The first part of the current review summarizes the genetic loci associated with blood pressure/ hypertension identified by genome-wide association studies (GWAS) from January 2007 to September 2011, by race and chromosomal location. In the second part, we stress several important points in GWAS methodology, for example, selecting high-quality phenotypes and using multi-stage study design to increase the power studies to identify loci with minor effect. For statistical analysis, besides multiple testing correction and replication of the GWAS that have been introduced in previous reviews, computer-based genotype imputation has been described for its advantages in compensating GWAS genotyping failures. Although GWAS identifies many unknown genetic variants and improves our understanding for the pathogenesis of hypertension, the loci related to blood pressure / hypertension are common sequence variations with minor effect. The association studies are difficult to be replicated in different populations. Further studies are expected including extensive functional studies and fine mapping using advanced techniques, such as whole genome exon sequencing and pathway analysis, as well as epigenetic study to elucidate the etiology of human essential hypertension.

Cite this article

XU Rui-Wei, YAN Wei-Li . Advances in genome-wide association studies on essential hypertension[J]. Hereditas(Beijing), 2012 , 34(7) : 793 -809 . DOI: 10.3724/SP.J.1005.2012.00793

References

[1] Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J. Global burden of hypertension: Analysis of worldwide data. Lancet, 2005, 365(9455): 217-223.
[2] Lawes CMM, Hoorn SV, Rodgers A. Global burden of blood-pressure-related disease, 2001. Lancet, 2008, 371 (9623): 1513-1518.
[3] Feinleib M, Garrison RJ, Fabsitz R, Christian JC, Hrubec Z, Borhani NO, Kannel WB, Rosenman R, Schwartz JT, Wagner JO. The NHLBI twin study of cardiovascular disease risk factors: Methodology and summary of results. Am J Epidemiol, 1977, 106(4): 284-285.
[4] Hunt SC, Hasstedt SJ, Kuida H, Stults BM, Hopkins PN, Williams RR. Genetic heritability and common environmental components of resting and stressed blood pressures, lipids, and body mass index in Utah pedigrees and twins. Am J Epidemiol, 1989, 129(3): 625-638.
[5] Pearson TA, Manolio TA. How to interpret a genome-wide association study. JAMA J Am Med Assoc, 2008, 299(11): 1335-1344.
[6] Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 2007, 447(7145): 661-678.
[7] Levy D, Larson MG, Benjamin EJ, Newton-Cheh C, Wang TJ, Hwang SJ, Vasan RS, Mitchell GF. Framingham heart study 100K project: Genome-wide associations for blood pressure and arterial stiffness. BMC Med Genet, 2007, 8(Suppl. 1): S3.
[8] Ehret GB, Morrison AC, O'Connor AA, Grove ML, Baird L, Schwander K, Weder A, Cooper RS, Rao DC, Hunt SC, Boerwinkle E, Chakravarti A. Replication of the wellcome trust genome-wide association study of essential hypertension: The family blood pressure program. Eur J Hum Genet, 2008, 16(12): 1507-1511.
[9] Wang Y, O'Connell JR, McArdle PF, Wade JB, Dorff SE, Shah SJ, Shi XL, Pan L, Rampersaud E, Shen HQ, Kim JD, Subramanya AR, Steinle NI, Parsa A, Ober CC, Welling PA, Chakravarti A, Weder AB, Cooper RS, Mitchell BD, Shuldiner AR, Chang YPC. Whole-genome association study identifies STK39 as a hypertension susceptibility gene. Proc Natl Acad Sci USA, 2009, 106(1): 226-231.
[10] Org E, Eyheramendy S, Juhanson P, Gieger C, Lichtner P, Klopp N, Veldre G, Döring A, Viigimaa M, Sõber S, Tomberg K, Eckstein G, Kelgo P, Rebane T, Shaw- Hawkins S, Howard P, Onipinla A, Dobson RJ, Newhouse SJ, Brown M, Dominiczak A, Connell J, Samani N, Farrall M, Caulfield MJ, Munroe PB, Illig T, Wichmann HE, Meitinger T, Laan M. Genome-wide scan identifies CDH13 as a novel susceptibility locus contributing to blood pressure determination in two european populations. Hum Mol Genet, 2009, 18(12): 2288-2296.
[11] Roslin NM, Hamid JS, Paterson AD, Beyene J. Genome-wide association analysis of cardiovascular-related quantitative traits in the framingham heart study. BMC Proc, 2009, 3(Suppl. 7): S117.
[12] Levy D, Ehret GB, Rice K, Verwoert GC, Launer LJ, Dehghan A, Glazer NL, Morrison AC, Johnson AD, Aspelund T, Aulchenko Y, Lumley T, Köttgen A, Vasan RS, Rivadeneira F, Eiriksdottir G, Guo XQ, Arking DE, Mitchell GF, Mattace-Raso FUS, Smith AV, Taylor K, Scharpf RB, Hwang SJ, Sijbrands EJG, Bis J, Harris TB, Ganesh SK, O'Donnell CJ, Hofman A, Rotter JI, Coresh J, Benjamin EJ, Uitterlinden AG, Heiss G, Fox CS, Witteman JCM, Boerwinkle E, Wang TJ, Gudnason V, Larson MG, Chakravarti A, Psaty BM, van Duijn CM. Genome-wide association study of blood pressure and hypertension. Nat Genet, 2009, 41(6): 677-687.
[13] Newton-Cheh C, Johnson T, Gateva V, Tobin MD, Bochud M, Coin L, Najjar SS, Zhao JH, Heath SC, Eyheramendy S, Papadakis K, Voight BF, Scott LJ, Zhang F, Farrall M, Munroe PB. Genome-wide association study identifies eight loci associated with blood pressure. Nat Genet, 2009, 41(6): 666-676.
[14] Zhu XF, Young JH, Fox E, Keating BJ, Franceschini
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