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

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Shendre, Aditi
    • Other Affiliation: Department of Epidemiology; University of Alabama at Birmingham
  • Wiener, Howard W.
    • Other Affiliation: Department of Epidemiology; University of Alabama at Birmingham
  • Irvin, Marguerite R.
    • Other Affiliation: Department of Epidemiology; University of Alabama at Birmingham
  • Aouizerat, Bradley E.
    • Other Affiliation: Department of Oral and Maxillofacial Surgery; New York University
  • Overton, Edgar T.
    • Other Affiliation: Division of Infectious Diseases; Department of Medicine; University of Alabama at Birmingham
  • Lazar, Jason
    • Other Affiliation: Department of Medicine; State University of New York; Downstate Medical Center
  • Liu, Chenglong
    • Other Affiliation: Department of Medicine; Georgetown University Medical Center
  • Hodis, Howard N.
    • Other Affiliation: Atherosclerosis Research Unit; University of Southern California
  • Limdi, Nita A.
    • Other Affiliation: Department of Neurology; University of Alabama at Birmingham
  • Weber, Kathleen M.
    • Other Affiliation: Cook County Health and Hospital System/Hektoen Institute of Medicine
  • Gange, Stephen J.
    • Other Affiliation: Department of Epidemiology; Johns Hopkins Bloomberg School of Public Health
  • Zhi, Degui
    • Other Affiliation: School of Biomedical Informatics; University of Texas Health Science Center at Houston
  • Floris-Moore, Michelle A.
    • Affiliation: School of Medicine, Department of Medicine
  • Ofotokun, Ighovwerha
    • Other Affiliation: Department of Medicine/Infectious Diseases; Emory University; Grady Healthcare System
  • Qi, Qibin
    • Other Affiliation: Department of Epidemiology and Population Health; Albert Einstein College of Medicine
  • Hanna, David B.
    • Other Affiliation: Department of Epidemiology and Population Health; Albert Einstein College of Medicine
  • Kaplan, Robert C.
    • Other Affiliation: Department of Epidemiology and Population Health; Albert Einstein College of Medicine
  • Shrestha, Sadeep
    • Other Affiliation: Department of Epidemiology; University of Alabama at Birmingham
Abstract
  • 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.
Date of publication
Keyword
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
Journal title
  • PloS One
Journal volume
  • 12
Journal issue
  • 12
Page start
  • e0188725
Language
  • English
ISSN
  • 1932-6203

Relations

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details PubMedCentral-PMC5714351.pdf 2017 Public Download