Title | Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration. |
Publication Type | Publication |
Year | 2023 |
Authors | Han X, Lains I, Li J, Li J, Chen Y, Yu B, Qi Q, Boerwinkle E, Kaplan R, Thyagarajan B, Daviglus M, Joslin CE, Cai J, Guasch-Ferré M, Tobias DK, Rimm E, Ascherio A, Costenbader K, Karlson E, Mucci L, A Eliassen H, Zeleznik O, Miller J, Vavvas DG, Kim IK, Silva R, Miller J, Hu F, Willett W, Lasky-Su J, Kraft P, J Richards B, MacGregor S, Husain D, Liang L |
Journal | Cell Rep Med |
Volume | 4 |
Issue | 7 |
Pagination | 101085 |
Date Published | 2023 Jul 18 |
ISSN | 2666-3791 |
Keywords | Aged, Bayes Theorem, genome-wide association study, Humans, Macular Degeneration, Metabolome, Metabolomics |
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. |
DOI | 10.1016/j.xcrm.2023.101085 |
Alternate Journal | Cell Rep Med |
PubMed ID | 37348500 |
PubMed Central ID | PMC10394104 |
Grant List | R01 AR049880 / AR / NIAMS NIH HHS / United States U01 CA176726 / CA / NCI NIH HHS / United States U01 CA167552 / CA / NCI NIH HHS / United States R01 EY030088 / EY / NEI NIH HHS / United States R00 DK122128 / DK / NIDDK NIH HHS / United States R01 CA049449 / CA / NCI NIH HHS / United States R01 CA067262 / CA / NCI NIH HHS / United States UM1 CA186107 / CA / NCI NIH HHS / United States |
Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration.
MS#:
0892
ECI:
Yes
Manuscript Affiliation:
Field Center: Bronx (Einstein College of Medicine)
Manuscript Status:
Published