Publication Date
3-2-2023
Journal
American Journal of Human Genetics
DOI
10.1016/j.ajhg.2023.02.002
PMID
36809768
PMCID
PMC10027475
PubMedCentral® Posted Date
2-20-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, Biological Specimen Banks, Biomarkers, Lipids, United Kingdom, Polymorphism, Single Nucleotide, metabolomics, UK Biobank, rare variant, collapsing analyses, metabologenomics, mQTL, exome sequencing.
Abstract
Genome-wide association studies (GWASs) have established the contribution of common and low-frequency variants to metabolic blood measurements in the UK Biobank (UKB). To complement existing GWAS findings, we assessed the contribution of rare protein-coding variants in relation to 355 metabolic blood measurements-including 325 predominantly lipid-related nuclear magnetic resonance (NMR)-derived blood metabolite measurements (Nightingale Health Plc) and 30 clinical blood biomarkers-using 412,393 exome sequences from four genetically diverse ancestries in the UKB. Gene-level collapsing analyses were conducted to evaluate a diverse range of rare-variant architectures for the metabolic blood measurements. Altogether, we identified significant associations (p < 1 × 10
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