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

Abstract

Objectives: People with HIV (PWH) are more likely to develop electrocardiogram (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, eleven 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.