Genome-wide metabolite quantitative trait loci analysis (mQTL) in red blood cells from volunteer blood donors

• DOI: 10.1016/j.jbc.2022.102706
• Publication Date: 2022-11-15T01:28:53Z
• Authors: Amy Moore; Michael P. Busch; Karolina Dziewulska; Richard O. Francis; Eldad A. Hod; James C. Zimring; Angelo D’Alessandro; Grier P. Page
• Keywords: Genome-wide Association Study

The red blood cell (RBC)-Omics study, part of the larger NHLBI-funded Recipient Epidemiology and Donor Evaluation Study (REDS-III), aims to understand genetic contribution donor RBC characteristics. Previous work identified demographic, behavioral, genetic, metabolic underpinnings donation, storage, (to a lesser extent) transfusion outcomes, but none have yet linked bodies work. We performed genome-wide association (GWA) analysis using RBC-Omics study participants with generated untargeted metabolomics data identify metabolite quantitative trait loci in RBCs. GWA analyses 382 metabolites 243 individuals imputed 1000 Genomes Project phase 3 all-ancestry reference panel. Analyses were conducted ProbABEL adjusted for sex, age, donation center, number whole donations past 2 years, first 10 principal components ancestry. Our results 423 independent associated 132 (<i>p</i> < 5×10^–8). Potentially novel locus-metabolite associations region encoding heme transporter FLVCR1 choline lysophosphatidylcholine acetyltransferase LPCAT3 lysophosphatidylserine 16.0, 18.0, 18.1, 18.2; these are supported by published rare disease mouse studies. also confirmed previous associations, including N(6)-methyl-L-lysine protein PYROXD2 various carnitines SLC22A16. Association between pyruvate levels G6PD polymorphisms was validated an cohort murine models deficiency (African Mediterranean variants). demonstrate that it is possible perform metabolomics-scale modest, trans-ancestry sample size.