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Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration.

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
Eliassen AH
Zeleznik O
Miller J
Vavvas DG
Kim IK
Silva R
Miller J
Hu F
Willett W
Lasky-Su J
Kraft P
Richards JB
MacGregor S
Husain D
Liang L
Source :
Cell reports. Medicine [Cell Rep Med] 2023 Jul 18; Vol. 4 (7), pp. 101085. Date of Electronic Publication: 2023 Jun 21.
Publication Year :
2023

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.<br />Competing Interests: Declaration of interests J.B.R.’s institution has received investigator-initiated grant funding from Eli Lilly, GlaxoSmithKline, and Biogen for projects unrelated to this research. He is the CEO of 5 Prime Sciences (www.5primesciences.com), which provides research services for biotech, pharma, and venture capital companies for projects unrelated to this research. J.L.-S. is a scientific advisor to Precion Inc. D.G.V. is a consultant for Sumitomo/Sunovion, Inhibikase, OLix Pharma, Twenty/Twenty, and Valitor.<br /> (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
2666-3791
Volume :
4
Issue :
7
Database :
MEDLINE
Journal :
Cell reports. Medicine
Publication Type :
Academic Journal
Accession number :
37348500
Full Text :
https://doi.org/10.1016/j.xcrm.2023.101085