The Causal Association Between HIV and Atrial Fibrillation: A Mendelian Randomization Study

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Human immunodeficiency virus (HIV) infection and atrial fibrillation (AF) (n=756201). Intervention: Genetically predicted HIV susceptibility vs. Absence of genetic predisposition to HIV susceptibility. Primary outcome: Atrial fibrillation (AF) risk assessed via inverse-variance weighted (IVW) univariable Mendelian randomization (OR 1.016, 95% CI 1.004-1.029, p=0.01).

Q: What does this research mean for the field?

Genetically predicted susceptibility to HIV infection is causally associated with a modestly increased risk of atrial fibrillation in individuals of European ancestry. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Yujia Wu; Wanqian Pan; Hang Li; Rui Han; Minyu Zhou; Xintao Li; 蒋廷波; Xichen Chai

doi:10.1155/cdr/7645834

January 1, 2026Cardiovascular TherapeuticsOpen Access

The Causal Association Between HIV and Atrial Fibrillation: A Mendelian Randomization Study

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Why the study?

Previous evidence suggested an elevated risk of AF among HIV patients, but it remained unclear whether this relationship is causal.

Does genetically predicted HIV susceptibility causally increase the risk of atrial fibrillation in individuals of European ancestry?

Key Points

To determine whether human immunodeficiency virus infection exerts a causal effect on the risk of developing atrial fibrillation.
Applied a two-sample bidirectional univariable and multivariable Mendelian randomization framework using summary statistics from genome-wide association studies.
Identified genetic instruments for HIV susceptibility from the FinnGen project (357 cases, 218,435 controls) and atrial fibrillation from a meta-analysis (55,114 cases, 482,295 controls) among participants of European ancestry.
Adjusted multivariable Mendelian randomization analyses for covariates including smoking, alcohol use disorder, obesity, hypertension, myocardial infarction, and GrimAge epigenetic aging.
Univariate inverse-variance weighted Mendelian randomization showed a causal association between HIV infection and atrial fibrillation risk (OR = 1.016, 95% CI: 1.004-1.029, p = 0.01), with no significant heterogeneity or pleiotropy.
Multivariable Mendelian randomization confirmed an independent causal relationship between HIV infection and atrial fibrillation after adjusting for potential confounders (OR = 1.016, 95% CI: 1.002-1.031, p = 0.03).
Reverse Mendelian randomization found no significant causal effect of atrial fibrillation on HIV risk (OR = 1.064, 95% CI: 0.839-1.350, p = 0.61).

Study Design

Type

Observational (n=756,201)

Multicenter

Yes

Structured PICO

Does genetically predicted HIV susceptibility causally increase the risk of atrial fibrillation in individuals of European ancestry?

P

Population

Two-sample Mendelian randomization study analyzing genome-wide association study summary data from European-ancestry cohorts comprising 218,792 participants for HIV susceptibility (357 cases, 218,435 controls) and 537,409 participants for atrial fibrillation (55,114 cases, 482,295 controls).

E

Exposure

Genetically predicted HIV infection susceptibility (instrumented using 8 single nucleotide polymorphisms at p < 5 × 10^-6 in univariable and multivariable Mendelian randomization models)

C

Comparator

Lower genetically predicted HIV susceptibility / general population controls without genetic predisposition

O

Outcome

Atrial fibrillation (AF) risk evaluated via random-effects inverse-variance weighted (IVW) two-sample Mendelian randomizationhard clinical

Main Result

Odds Ratio: 1.016 (95% CI 1.004–1.029)

p-value: p=0.01

Limitations

Exposure variable captures genetically predicted HIV susceptibility rather than clinical HIV infection course, viral load, CD4+ count, or ART status
Limited number of instrumental variables (8 SNPs using a relaxed threshold of p < 5e-6) explaining only 0.0836% of variance with low statistical power (~5%)
Risk of weak instrument bias in multivariable MR models (conditional F-statistics fell below 10 when adjusting for all six confounders simultaneously)
Restricted to individuals of European ancestry, limiting generalizability to other populations
Did not directly evaluate underlying biological mechanisms
Exposure captures genetic susceptibility to HIV rather than clinical HIV progression, viral load, immune status, or antiretroviral therapy effects
Small number of HIV cases (357) and genetic instruments (8 SNPs explaining 0.0836% variance), resulting in low statistical power (~5%)
Conditional F-statistics fell below 10 (range 1.99-7.79) in the fully adjusted multivariable MR model, indicating risk of weak instrument bias
All GWAS datasets were restricted to European ancestry, limiting generalizability
Biological mechanisms were not directly tested

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Implication

This Mendelian randomization study provides suggestive genetic evidence that HIV susceptibility is modestly and independently associated with an increased risk of atrial fibrillation in individuals of European ancestry, even after accounting for traditional cardiovascular risk factors and biological aging.

Abstract

BACKGROUND: Human immunodeficiency virus (HIV) associated cardiovascular burden has become increasingly prominent. Previous evidence suggested an elevated risk of atrial fibrillation (AF) among HIV patients; it remains unclear whether this relationship is causal. Our study was to investigate the causal effect of HIV infection on AF. METHODS: A two-sample Mendelian randomization (MR) framework was implemented to examine causal association between HIV infection and AF. Summary data on the association of single nucleotide polymorphisms (SNPs) with HIV infection were obtained from public genome-wide association studies. Statistical data for SNPs-AF associations were extracted from OPENGWAS datasets. Bidirectional univariable and multivariable MR analyses were conducted to assess causal effects. RESULTS: Univariate MR analysis revealed a suggestive causal association between HIV infection and AF risk (IVW: OR = 1.016, 95% CI: 1.004-1.029, p = 0.01), with no significant heterogeneity or pleiotropy. None significant effect was observed for AF on HIV risk (OR = 1.064, 95% CI: 0.839-1.350, p = 0.61). Multivariable MR analysis revealed an independent association between HIV infection and AF after adjusting for potential confounders (OR = 1.016, 95% CI: 1.002-1.031, p = 0.03). CONCLUSION: Our study found evidence supporting a causal association between genetically predicted HIV susceptibility and AF in individuals of European ancestry, suggesting that HIV-related pathways may contribute to AF development.

Discussion

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Cite This Study

Wu et al. (2026) conducted an observational in Human immunodeficiency virus (HIV) infection and atrial fibrillation (AF) (n=756,201). Genetically predicted HIV susceptibility vs. Absence of genetic predisposition to HIV susceptibility was evaluated on Atrial fibrillation (AF) risk assessed via inverse-variance weighted (IVW) univariable Mendelian randomization (OR 1.016, 95% CI 1.004-1.029, p=0.01).

synapsesocial.com/papers/6af9ebcdd393cbc380a0503f https://doi.org/10.1155/cdr/7645834

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The Causal Association Between HIV and Atrial Fibrillation: A Mendelian Randomization Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

The Causal Association Between HIV and Atrial Fibrillation: A Mendelian Randomization Study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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