Faculty, Staff and Student Publications

Language

English

Publication Date

7-18-2023

Journal

Cell Reports Medicine

DOI

10.1016/j.xcrm.2023.101085

PMID

37348500

PMCID

PMC10394104

PubMedCentral® Posted Date

7-18-2023

PubMedCentral® Full Text Version

Post-print

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

Published Open-Access

yes

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