학술논문

Genome-wide Association Analysis of Blood-Pressure Traits in African-Ancestry Individuals Reveals Common Associated Genes in African and Non-African Populations
Document Type
article
Author
Franceschini, NoraFox, ErvinZhang, ZhaogongEdwards, Todd LNalls, Michael ASung, Yun JuTayo, Bamidele OSun, Yan VGottesman, OmriAdeyemo, AdebawoleJohnson, Andrew DYoung, J HunterRice, KenDuan, QingChen, FangLi, YunTang, HuaFornage, MyriamKeene, Keith LAndrews, Jeanette SSmith, Jennifer AFaul, Jessica DGuangfa, ZhangGuo, WeiLiu, YuMurray, Sarah SMusani, Solomon KSrinivasan, SathanurEdwards, Digna R VelezWang, HemingBecker, Lewis CBovet, PascalBochud, MurielleBroeckel, UlrichBurnier, MichelCarty, CaraChasman, Daniel IEhret, GeorgChen, Wei-MinChen, GuanjieChen, WeiDing, JingzhongDreisbach, Albert WEvans, Michele KGuo, XiuqingGarcia, Melissa EJensen, RichKeller, Margaux FLettre, GuillaumeLotay, VaneetMartin, Lisa WMoore, Jason HMorrison, Alanna CMosley, Thomas HOgunniyi, AdesolaPalmas, WalterPapanicolaou, GeorgePenman, AlanPolak, Joseph FRidker, Paul MSalako, BabatundeSingleton, Andrew BShriner, DanielTaylor, Kent DVasan, RamachandranWiggins, KerriWilliams, Scott MYanek, Lisa RZhao, WeiZonderman, Alan BBecker, Diane MBerenson, GeraldBoerwinkle, EricBottinger, ErwinCushman, MaryEaton, CharlesNyberg, FredrikHeiss, GerardoHirschhron, Joel NHoward, Virginia JKarczewsk, Konrad JLanktree, Matthew BLiu, KiangLiu, YongmeiLoos, RuthMargolis, KarenSnyder, MichaelConsortium, the Asian Genetic Epidemiology NetworkGo, Min JinKim, Young JinLee, Jong-YoungJeon, Jae-PilKim, Sung SooHan, Bok-GheeCho, Yoon ShinSim, XuelingTay, Wan TingOng, Rick Twee HeeSeielstad, MarkLiu, Jian Jun
Source
American Journal of Human Genetics. 93(3)
Subject
Epidemiology
Biological Sciences
Health Sciences
Genetics
Cardiovascular
Human Genome
Aetiology
2.1 Biological and endogenous factors
Africa
Black People
Blood Pressure
Cohort Studies
Databases
Genetic
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Polymorphism
Single Nucleotide
Quantitative Trait
Heritable
Reproducibility of Results
Asian Genetic Epidemiology Network Consortium
Medical and Health Sciences
Genetics & Heredity
Biological sciences
Biomedical and clinical sciences
Health sciences
Language
Abstract
High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10(-8)) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.