428: Genetic regulation of plasma metabolites in people with HIV

Ait Oumelloul M et al., Human Genetics and Genomics Advances - Untargeted plasma metabolomics (1,930 features) in 1,244 participants of the Swiss HIV Cohort Study were paired with genome-wide genotypes to map genetic influences on metabolite levels, test colocalization with eQTLs, and apply Mendelian randomization to probe causal links with aging-related biomarkers and diseases. Key terms: HIV, metabolomics, GWAS, Mendelian randomization, NAT8.

Study Highlights:
The study performed GWAS on 1,930 putative plasma metabolites measured by untargeted mass spectrometry in 1,244 people with HIV and identified 27 metabolites associated with 12 genetic loci, including NAT8, FUT2, PYROXD2, and FADS. Colocalization analyses found that 24 of the 27 metabolite loci overlapped with tissue eQTLs, linking genetic variants to gene expression and metabolite variation. Mendelian randomization using MR-link-2 provided evidence for putative causal relationships, notably genetically higher N-acetylcitrulline associated with lower serum creatinine (protective for kidney function) and chorismate linked to higher cholesterol and triglycerides. Sensitivity analyses across ancestries and sex and partial replication in non-HIV data supported the robustness of key signals.

Conclusion:
Integrating untargeted metabolomics with GWAS, eQTL colocalization, and MR in people with HIV revealed host genetic regulation of plasma metabolites, identified colocalized expression signals, and suggested causal links between specific metabolites and kidney and lipid biomarkers, highlighting targets for follow-up and the utility of multi-omics for precision comorbidity research in this population.

Music:
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Article title:
Genome-wide association study of untargeted plasma metabolomic profiles identifies host genetic regulation in people with HIV

First author:
Ait Oumelloul M

Journal:
Human Genetics and Genomics Advances

DOI:
10.1016/j.xhgg.2026.100635

Reference:
Ait Oumelloul M, van der Graaf A, Tang S, Thorball CW, Labarile M, Saadat A, Timonina V, Schöpf IC, Wandeler G, Nemeth J, Cavassini M, Calmy A, Schmid P, Stöckle M, Elzi L, Zamboni N, Kouyos RD, Tarr PE, Fellay J; Swiss HIV Cohort Study. Genome-wide association study of untargeted plasma metabolomic profiles identifies host genetic regulation in people with HIV. Human Genetics and Genomics Advances. 2026;7:100635. https://doi.org/10.1016/j.xhgg.2026.100635

License:
This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/

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Episode link: https://basebybase.com/episodes/genetic-metabolomics-hiv-428

QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2026-07-23.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited portions include study design and population, untargeted metabolomics, GWAS of metabolites, eQTL colocalization, Mendelian randomization analyses, and key metabolite–gene–disease links (NAT8/N-acetylcitrulline, chorismate, F11/5-HTP), along with limitations and clinical implications discussed in the transcrip...