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. 2023 Oct 1;37(12):1871-1882.
doi: 10.1097/QAD.0000000000003647. Epub 2023 Jul 12.

Differential genome-wide associated variants and enriched pathways of ECG parameters among people with versus without HIV

Jiayu He  1   2   3 , Yingying Ding  1   2 , Haijiang Lin  1   4 , Xing Liu  1   2 , Xiaoxiao Chen  1   4 , Weiwei Shen  4 , Sujuan Zhou  1   2   3 , Cheng Feng  1   2 , Miaochen Wang  1   2 , Jingjing Xia  1   2 , Na He  1   2   3
Affiliations

Differential genome-wide associated variants and enriched pathways of ECG parameters among people with versus without HIV

Jiayu He et al. AIDS. .

Abstract

Objectives: People with HIV (PWH) are more likely to develop ECG abnormalities. Substantial evidence exists for genetic contribution to ECG parameters among general population. However, whether and how would host genome associate with ECG parameters among PWH is unclear. Our research aims to analyze and compare genetic variants, mapped genes, and enriched pathways of ECG parameters among PWH and HIV-negative controls.

Design: A cross-sectional study.

Method: We performed a large original genome-wide association study (GWAS) of ECG parameters among PWH ( n = 1730) and HIV-negative controls ( n = 3746). Genome-wide interaction analyses were also conducted.

Results: A total of 18 novel variants were detected among PWH, six for PR interval including rs76345397 at ATL2 , 11 for QRS duration including rs10483994 at KCNK10 and rs2478830 at JCAD , and one for QTc interval (rs9815364). Among HIV-negative controls, we identified variants located at previously reported ECG-related genes ( SCN5A , CNOT1 ). Genetic variants had a significant interaction with HIV infection ( P < 5 × 10 -8 ), implying that HIV infection and host genome might jointly influence ECG parameters. Mapped genes for PR interval and QRS duration among PWH were enriched in the biological process of viral genome replication and host response to virus, respectively, whereas enriched pathways for PR interval among HIV-negative controls were in the cellular component of voltage-gated sodium channel complex.

Conclusion: The present GWAS indicated a distinctive impact of host genome on quantitative ECG parameters among PWH. Different from HIV-negative controls, host genome might influence the cardiac electrical activity by interfering with HIV viral infection, production, and latency among PWH.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Fig. 1
Fig. 1
Manhattan plots and qq plots of SNPs associated with PR interval (a, b), QRS duration (c, d), and QTc interval (e, f) among people with HIV.
Fig. 2
Fig. 2
Cross-locus interactions for genomic regions associated with PR interval (a, b, c) and QRS duration (d) among people with HIV.
Fig. 3
Fig. 3
Significant bubble diagrams of GO biological process, molecular function, and cell components for PR interval among PWH (a), PR interval among HIV-negative controls (b), and QRS duration among PWH (c).
See this image and copyright information in PMC

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