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Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

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.

SUBMITTER: Franceschini N

PROVIDER: S-EPMC3769920 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

Franceschini Nora N Fox Ervin E Zhang Zhaogong Z Edwards Todd L TL Nalls Michael A MA Sung Yun Ju YJ Tayo Bamidele O BO Sun Yan V YV Gottesman Omri O Adeyemo Adebawole A Johnson Andrew D AD Young J Hunter JH Rice Ken K Duan Qing Q Chen Fang F Li Yun Y Tang Hua H Fornage Myriam M Keene Keith L KL Andrews Jeanette S JS Smith Jennifer A JA Faul Jessica D JD Guangfa Zhang Z Guo Wei W Liu Yu Y Murray Sarah S SS Musani Solomon K SK Srinivasan Sathanur S Velez Edwards Digna R DR Wang Heming H Becker Lewis C LC Bovet Pascal P Bochud Murielle M Broeckel Ulrich U Burnier Michel M Carty Cara C Chasman Daniel I DI Ehret Georg G Chen Wei-Min WM Chen Guanjie G Chen Wei W Ding Jingzhong J Dreisbach Albert W AW Evans Michele K MK Guo Xiuqing X Garcia Melissa E ME Jensen Rich R Keller Margaux F MF Lettre Guillaume G Lotay Vaneet V Martin Lisa W LW Moore Jason H JH Morrison Alanna C AC Mosley Thomas H TH Ogunniyi Adesola A Palmas Walter W Papanicolaou George G Penman Alan A Polak Joseph F JF Ridker Paul M PM Salako Babatunde B Singleton Andrew B AB Shriner Daniel D Taylor Kent D KD Vasan Ramachandran R Wiggins Kerri K Williams Scott M SM Yanek Lisa R LR Zhao Wei W Zonderman Alan B AB Becker Diane M DM Berenson Gerald G Boerwinkle Eric E Bottinger Erwin E Cushman Mary M Eaton Charles C Nyberg Fredrik F Heiss Gerardo G Hirschhron Joel N JN Howard Virginia J VJ Karczewsk Konrad J KJ Lanktree Matthew B MB Liu Kiang K Liu Yongmei Y Loos Ruth R Margolis Karen K Snyder Michael M Psaty Bruce M BM Schork Nicholas J NJ Weir David R DR Rotimi Charles N CN Sale Michele M MM Harris Tamara T Kardia Sharon L R SL Hunt Steven C SC Arnett Donna D Redline Susan S Cooper Richard S RS Risch Neil J NJ Rao D C DC Rotter Jerome I JI Chakravarti Aravinda A Reiner Alex P AP Levy Daniel D Keating Brendan J BJ Zhu Xiaofeng X

American journal of human genetics 20130822 3

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 ...[more]

PMID: 23972371

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Project description:Background: Despite hypertension being highly prevalent in individuals with African-ancestry, they are under-represented in large genome-wide association studies. Inclusion of African participants is essential to better understand genetic associations with blood pressure-related traits in Africans. This systematic review critically evaluates existing studies with African-ancestry participants and identifies knowledge gaps. Methods: We followed the PRISMA protocol, HuGE Review handbook to identify literature on original research, in English, on genetic association studies for blood pressure-related traits (systolic and diastolic blood pressure, pulse and mean-arterial pressure, and hypertension) in populations with African-ancestry (January 2007 to April 2020). A narrative synthesis of the evidence was conducted. Results: Twelve studies with African-ancestry participants met the eligibility criteria, within which 10 studies met the additional genetic association data criteria (i.e., reporting only on African-ancestry participants). Across the five blood pressure-related traits, 26 genome-wide significantly associated SNPs were identified, with six SNPs linked to more than one trait, illustrating pleiotropic effects. Among the SNP associations, 12 had not previously been described in non-African studies. Discussion: The limited number of relevant studies highlights the dearth of genomic association studies on participants with African-ancestry, especially those located within Africa. Variations in study methodology, participant inclusion, adjustment for covariates (e.g., antihypertensive medication) and relatively small sample sizes make comparisons challenging, and have resulted in fewer significant associations, compared to large European studies. Regional variation in the prevalence and associated risk factors of hypertension across Africa makes a compelling argument to develop African cohorts to facilitate large genomic studies, using African-centric arrays. Data harmonisation and comparable study designs, such as described in the H3Africa CHAIR initiative, provide a good example toward achieving this goal. Other relevant information: SS and J-TB were funded by the South African National Research Foundation. MR is a South African Research Chair in Genomics and Bioinformatics of African populations hosted by the University of the Witwatersrand, funded by the Department of Science and Innovation, and administered by the NRF. This review was registered at PROSPERO (registration number: CRD42020179221) and OSF (registration DOI: 10.17605/OSF.IO/QT2HA).

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Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

Publications

Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations.

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