Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions

Jiayu He; Haijiang Lin; Yingying Ding; Xing Liu; Kelin Xu; Xiaoxiao Chen; Weiwei Shen; Sujuan Zhou; Miaochen Wang; Jingjing Xia; Na He

doi:10.1186/s12967-022-03817-6

Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions

J Transl Med. 2022 Dec 20;20(1):609. doi: 10.1186/s12967-022-03817-6.

Authors

Jiayu He^#^{1

2

3}, Haijiang Lin^#^{1

4}, Yingying Ding^{1

2}, Xing Liu^{1

2}, Kelin Xu⁵, Xiaoxiao Chen^{1

4}, Weiwei Shen⁴, Sujuan Zhou^{1

2

3}, Miaochen Wang^{1

2}, Jingjing Xia^{1

2}, Na He^{6

7

8}

Affiliations

¹ Department of Epidemiology, School of Public Health, and Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China.
² Yi-Wu Research Institute, Fudan University, Shanghai, China.
³ Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China.
⁴ Taizhou City Center for Disease Control and Prevention, Taizhou, Zhejiang, China.
⁵ Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China.
⁶ Department of Epidemiology, School of Public Health, and Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China. nhe@fudan.edu.cn.
⁷ Yi-Wu Research Institute, Fudan University, Shanghai, China. nhe@fudan.edu.cn.
⁸ Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University, Shanghai, China. nhe@fudan.edu.cn.

^# Contributed equally.

Abstract

Background: Genome-wide association studies (GWAS) have identified some variants associated with subclinical atherosclerosis (SCA) in general population but lacking sufficient validation. Besides traditional risk factors, whether and how would genetic variants associate with SCA among people with HIV (PWH) remains to be elucidated.

Method: A large original GWAS and gene-environment interaction analysis of SCA were conducted among Chinese PWH (n = 2850) and age/sex-matched HIV-negative controls (n = 5410). Subgroup analyses by age and functional annotations of variants were also performed.

Results: Different from HIV-negative counterparts, host genome had a greater impact on young PWH rather than the elders: one genome-wide significant variant (rs77741796, P = 2.20 × 10^-9) and eight suggestively significant variants (P < 1 × 10^-6) were identified to be specifically associated with SCA among PWH younger than 45 years. Seven genomic loci and 15 genes were mapped to play a potential role on SCA among young PWH, which were enriched in the biological processes of atrial cardiac muscle cell membrane repolarization and molecular function of protein kinase A subunit binding. Furthermore, genome-wide interaction analyses revealed significant HIV-gene interactions overall as well as gene-environment interactions with alcohol consumption, tobacco use and obesity among PWH. The identified gene-environment interaction on SCA among PWH might be useful for discovering high-risk individuals for the prevention of SCA, particularly among those with tobacco use and alcohol consumption.

Conclusion: The present study provides new clues for the genetic contribution of SCA among young PWH and is the starting point of precision intervention targeting HIV-related atherosclerosis.

Keywords: Chinese; GWAS; HIV; Interaction; Subclinical atherosclerosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Aged
Atherosclerosis* / complications
Atherosclerosis* / genetics
Gene-Environment Interaction
Genome-Wide Association Study
HIV Infections* / complications
HIV Infections* / genetics
Humans
Risk Factors