Crosstalk between Host Genome and Metabolome among People with HIV in South Africa

• Type of Material: Article
• Authors: Chang Liu, Emory University; Zicheng Wang, Emory University; Qin Hui, Emory University; Yiyun Chiang, Emory University; Junyu Chen, Emory University; Jaysingh Brijkumar, University of Kwazulu Natal; Johnathan Edwards, Emory University; Claudia Ordonez, Emory University; Matthew Dudgeon, Emory University; Henry Sunpath, University of Kwazulu Natal; Selvan Pillay, University of Kwazulu Natal; Pravi Moodley, University of Kwazulu Natal; Daniel R Kuritzkes, Harvard Medical School; Mohamed YS Moosa, University of Kwazulu Natal; Dean Jones, Emory University; Vincent Marconi, Emory University; Yan Sun, Emory University
• Language: English
• Date: 2022-07-01
• Publisher: MDPI
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by the authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3390/metabo12070624
• Title of Journal or Parent Work: METABOLITES
• Volume: 12
• Issue: 7
• Grant/Funding Information: This research was partly funded by the National Institute of Health grant number R01DK125187, and Emory CFAR grant number P30AI050409.
• Keywords: Life Sciences & Biomedicine; DISEASE; Science & Technology; RISK; WIDE ASSOCIATION; GWAS; African; BILIRUBIN LEVELS; metabolome; LOCI; HIV; SET; MASS-SPECTROMETRY; Biochemistry & Molecular Biology
• Research Categories: Health Sciences, Public Health; Health Sciences, Epidemiology; Health Sciences, Medicine and Surgery

Abstract

Genome-wide association studies (GWAS) of circulating metabolites have revealed the role of genetic regulation on the human metabolome. Most previous investigations focused on European ancestry, and few studies have been conducted among populations of African descent living in Africa, where the infectious disease burden is high (e.g., human immunodeficiency virus (HIV)). It is important to understand the genetic associations of the metabolome in diverse at-risk populations including people with HIV (PWH) living in Africa. After a thorough literature review, the reported significant gene–metabolite associations were tested among 490 PWH in South Africa. Linear regression was used to test associations between the candidate metabolites and genetic variants. GWAS of 154 plasma metabolites were performed to identify novel genetic associations. Among the 29 gene–metabolite associations identified in the literature, we replicated 10 in South Africans with HIV. The UGT1A cluster was associated with plasma levels of biliverdin and bilirubin; SLC16A9 and CPS1 were associated with carnitine and creatine, respectively. We also identified 22 genetic associations with metabolites using a genome-wide significance threshold (p-value < 5 × 10−8). In a GWAS of plasma metabolites in South African PWH, we replicated reported genetic associations across ancestries, and identified novel genetic associations using a metabolomics approach.