Faculty, Staff and Student Publications
Publication Date
7-18-2023
Journal
Cell Reports Medicine
Abstract
Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.
Keywords
Humans, Aged, Genome-Wide Association Study, Bayes Theorem, Macular Degeneration, Metabolomics, Metabolome, age-related macular degeneration, AMD, genome-wide association studies, GWASs, Nurses’ Health Study, NHS, Health Professionals Follow Up Study, HPFS, Canadian Longitudinal Study of Aging, CLSA, Hispanic Community Health Study/Study of Latinos, HCHS/SOL, Mendelian randomization, MR, genomics, metabolomics, UK Biobank
DOI
10.1016/j.xcrm.2023.101085
PMID
37348500
PMCID
PMC10394104
PubMedCentral® Posted Date
7-18-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Graphical Abstract
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Medical Genetics Commons, Public Health Commons