Journal Article

Genome-wide admixture and association study of subclinical atherosclerosis in the Women’s Interagency HIV Study (WIHS)

Shendre, Aditi, Kaplan, Robert C., Limdi, Nita A., Aouizerat, Bradley E., Liu, Chenglong, Hanna, David B., Shrestha, Sadeep, Weber, Kathleen M., Wiener, Howard W., Floris-Moore, Michelle A., Qi, Qibin, Overton, Edgar T., Lazar, Jason, Hodis, Howard N., Gange, Stephen J., Ofotokun, Ighovwerha, Irvin, Marguerite R., Zhi, Degui

2017

Overview

Cardiovascular disease (CVD) is a major comorbidity among HIV-infected individuals. Common carotid artery intima-media thickness (cCIMT) is a valid and reliable subclinical measure of atherosclerosis and is known to predict CVD. We performed genome-wide association (GWA) and admixture analysis among 682 HIV-positive and 288 HIV-negative Black, non-Hispanic women from the Women's Interagency HIV study (WIHS) cohort using a combined and stratified analysis approach. We found some suggestive associations but none of the SNPs reached genome-wide statistical significance in our GWAS analysis. The top GWAS SNPs were rs2280828 in the region intergenic to mediator complex subunit 30 and exostosin glycosyltransferase 1 (MED30 | EXT1) among all women, rs2907092 in the catenin delta 2 (CTNND2) gene among HIV-positive women, and rs7529733 in the region intergenic to family with sequence similarity 5, member C and regulator of G-protein signaling 18 (FAM5C | RGS18) genes among HIV-negative women. The most significant local European ancestry associations were in the region intergenic to the zinc finger and SCAN domain containing 5D gene and NADH: ubiquinone oxidoreductase complex assembly factor 1 (ZSCAN5D | NDUF1) pseudogene on chromosome 19 among all women, in the region intergenic to vomeronasal 1 receptor 6 pseudogene and zinc finger protein 845 (VN1R6P | ZNF845) gene on chromosome 19 among HIV-positive women, and in the region intergenic to the SEC23-interacting protein and phosphatidic acid phosphatase type 2 domain containing 1A (SEC23IP | PPAPDC1A) genes located on chromosome 10 among HIV-negative women. A number of previously identified SNP associations with cCIMT were also observed and included rs2572204 in the ryanodine receptor 3 (RYR3) and an admixture region in the secretion-regulating guanine nucleotide exchange factor (SERGEF) gene. We report several SNPs and gene regions in the GWAS and admixture analysis, some of which are common across HIV-positive and HIV-negative women as demonstrated using meta-analysis, and also across the two analytic approaches (i.e., GWA and admixture). These findings suggest that local European ancestry plays an important role in genetic associations of cCIMT among black women from WIHS along with other environmental factors that are related to CVD and may also be triggered by HIV. These findings warrant confirmation in independent samples.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acid phosphatase / Acquired immune deficiency syndrome / AIDS / Arteriosclerosis / Atherosclerosis / Atherosclerosis - complications / Atherosclerosis - genetics / Biology and Life Sciences / Black or African American - genetics / Cardiovascular disease / Cardiovascular diseases / Care and treatment / Carotid arteries / Carotid artery / Case-Control Studies / Chromosome 10 / Chromosome 19 / Cohort Studies / Comorbidity / Diabetes / Diagnosis / Environmental factors / Epidemiology / Female / Genes / Genetic aspects / Genome-wide association studies / Genome-Wide Association Study / Genomes / Glycosyltransferase / Guanine / Guanine nucleotide exchange factor / Heart attacks / HIV / HIV Infections - complications / HIV patients / Human immunodeficiency virus / Humans / Infections / Infectious diseases / Medicine / Medicine and Health Sciences / Mens health / Meta-analysis / NADH / Nicotinamide adenine dinucleotide / Oxidoreductase / People and Places / Phosphatidic acid / Physical Sciences / Public health / Research and Analysis Methods / Risk factors / Ryanodine receptors / Secretion / Signaling / Single-nucleotide polymorphism / Statistical analysis / Statistical methods / Stroke / Ubiquinone / Ubiquinone oxidoreductase / Ultrasonic imaging / Veins & arteries / White people / Womens health / Zinc / Zinc finger proteins