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Title: | Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration | Authors: | Han, Xikun Laíns, Inês Li, Jun Li, Jinglun Chen, Yiheng Yu, Bing Qi, Qibin Boerwinkle, Eric Kaplan, Robert Thyagarajan, Bharat Daviglus, Martha Joslin, Charlotte E. Cai, Jianwen Guasch-Ferré, Marta Tobias, Deirdre K. Rimm, Eric Ascherio, Alberto Costenbader, Karen Karlson, Elizabeth Mucci, Lorelei Eliassen, A Heather Zeleznik, Oana Miller, John Vavvas, Demetrios G. Kim, Ivana K. Silva, Rufino Miller, Joan Hu, Frank Willett, Walter Lasky-Su, Jessica Kraft, Peter Richards, J. Brent MacGregor, Stuart Husain, Deeba Liang, Liming |
Keywords: | AMD; CLSA; Canadian Longitudinal Study of Aging; GWASs; HCHS/SOL; HPFS; Health Professionals Follow Up Study; Hispanic Community Health Study/Study of Latinos; MR; Mendelian randomization; NHS; Nurses’ Health Study; UK Biobank; age-related macular degeneration; genome-wide association studies; genomics; metabolomics | Issue Date: | 18-Jul-2023 | Publisher: | Elsevier | Serial title, monograph or event: | Cell Reports Medicine | Volume: | 4 | Issue: | 7 | 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. | URI: | https://hdl.handle.net/10316/112203 | ISSN: | 26663791 | DOI: | 10.1016/j.xcrm.2023.101085 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais |
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