Genome-wide association study of coronary artery calcified atherosclerotic plaque in African Americans with type 2 diabetes

BMC Genetics

Research Article

S. Carrie Smith¹  Pamela J. Hicks¹  Donald W. Bowden¹  Jianzhao Xu¹  Nicholette D. Palmer²  Jasmin Divers³  W. Mark Brown³  Carl D. Langefeld³  Lingyi Lu³  Lynne E. Wagenknecht⁴  Gary C. Chan⁵  Barry I. Freedman⁵  Lijun Ma⁵  John S. Parks⁶  Solomon Musani⁷  Adolfo Correa⁷  Thomas C. Register⁸  James G. Wilson⁹  John Jeffrey Carr^1,10  James G. Terry^1,10  Herman A. Taylor^1,11  Sarah G. Buxbaum^1,12 

[1] Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA;Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA;Department of Biostatistical Sciences, Wake Forest School of Medicine, Medical Center Boulevard, 27157-1053, Winston-Salem, NC, USA;Department of Epidemiology, Wake Forest School of Medicine, Winston-Salem, NC, USA;Department of Internal Medicine-Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA;Department of Internal Medicine–Section on Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA;Department of Medicine, Jackson, MS, USA;Department of Pathology, Wake Forest School of Medicine, Winston-Salem, NC, USA;Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA;Department of Radiology and Vanderbilt Center for Translation and Clinical Cardiovascular Research (VTRACC), Vanderbilt University School of Medicine, Nashville, TN, USA;Morehouse School of Medicine, Morehouse College, Atlanta, Georgia;School of Public Health Initiative, Jackson State University, Jackson, MS, USA;

关键词: African Americans;    Coronary artery calcified atherosclerotic plaque;    Genome-wide association study;    Cardiovascular disease;    Type 2 diabetes;    Genetics;   

DOI  :  10.1186/s12863-017-0572-9

 received in 2017-02-10, accepted in 2017-11-23,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCoronary artery calcified atherosclerotic plaque (CAC) predicts cardiovascular disease (CVD). Despite exposure to more severe conventional CVD risk factors, African Americans (AAs) are less likely to develop CAC, and when they do, have markedly lower levels than European Americans. Genetic factors likely contribute to the observed ethnic differences. To identify genes associated with CAC in AAs with type 2 diabetes (T2D), a genome-wide association study (GWAS) was performed using the Illumina 5 M chip in 691 African American-Diabetes Heart Study participants (AA-DHS), with replication in 205 Jackson Heart Study (JHS) participants with T2D. Genetic association tests were performed on the genotyped and 1000 Genomes-imputed markers separately for each study, and combined in a meta-analysis.ResultsSingle nucleotide polymorphisms (SNPs), rs11353135 (2q22.1), rs16879003 (6p22.3), rs5014012, rs58071836 and rs10244825 (all on chromosome 7), rs10918777 (9q31.2), rs13331874 (16p13.3) and rs4459623 (18q12.1) were associated with presence and/or quantity of CAC in the AA-DHS and JHS, with meta-analysis p-values ≤8.0 × 10−7. The strongest result in AA-DHS alone was rs6491315 in the 13q32.1 region (parameter estimate (SE) = −1.14 (0.20); p-value = 9.1 × 10−9). This GWAS peak replicated a previously reported AA-DHS CAC admixture signal (rs7492028, LOD score 2.8).ConclusionsGenetic association between SNPs on chromosomes 2, 6, 7, 9, 16 and 18 and CAC were detected in AAs with T2D from AA-DHS and replicated in the JHS. These data support a role for genetic variation on these chromosomes as contributors to CAC in AAs with T2D, as well as to variation in CAC between populations of African and European ancestry.

【 授权许可】

CC BY   
© The Author(s). 2017