Genome-wide admixture and association study of subclinical atherosclerosis in the Women's Interagency HIV Study
Aditi Shendre1, Howard W Wiener1, Marguerite R Irvin1
1Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
Insights
This study explored genetic links to cardiovascular disease risk in Black women with and without HIV. Findings suggest European ancestry influences common carotid artery intima-media thickness, a marker for atherosclerosis.
Area of Science:
- Genetics and Genomics
- Cardiovascular Health
- HIV Research
Background:
- Cardiovascular disease (CVD) is a significant comorbidity in individuals with HIV.
- Common carotid artery intima-media thickness (cCIMT) is a validated marker for subclinical atherosclerosis and CVD risk.
- Understanding genetic factors contributing to CVD in HIV-infected populations is crucial.
Purpose of the Study:
- To investigate genome-wide associations (GWA) and admixture patterns related to cCIMT in Black women.
- To analyze these associations separately in HIV-positive and HIV-negative women.
- To identify genetic variants and ancestry-related regions associated with atherosclerosis markers.
Main Methods:
- Genome-wide association (GWA) and admixture analysis were performed on 682 HIV-positive and 288 HIV-negative Black, non-Hispanic women from the Women's Interagency HIV Study (WIHS).
- Combined and stratified analyses were used to assess genetic associations.
- Top single nucleotide polymorphisms (SNPs) and significant local ancestry regions were identified.
Main Results:
- No SNPs reached genome-wide statistical significance, but suggestive associations were found.
- Top GWAS SNPs included rs2280828 (MED30 | EXT1), rs2907092 (CTNND2), and rs7529733 (FAM5C | RGS18).
- Significant local European ancestry associations were identified on chromosomes 19 and 10, implicating genes like ZSCAN5D, NDUF1, VN1R6P, ZNF845, SEC23IP, and PPAPDC1A.
Conclusions:
- Local European ancestry appears to play a role in the genetic associations of cCIMT in Black women within the WIHS cohort.
- Findings suggest a complex interplay between genetic factors, local ancestry, and environmental influences on CVD risk in this population.
- Identified SNPs and gene regions warrant further investigation and validation in independent cohorts.
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.
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