TY - JOUR
T1 - Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration
AU - Han, Xikun
AU - Lains, Ines
AU - Li, Jun
AU - Li, Jinglun
AU - Chen, Yiheng
AU - Yu, Bing
AU - Qi, Qibin
AU - Boerwinkle, Eric
AU - Kaplan, Robert
AU - Thyagarajan, Bharat
AU - Daviglus, Martha
AU - Joslin, Charlotte E.
AU - Cai, Jianwen
AU - Guasch-Ferré, Marta
AU - Tobias, Deirdre K.
AU - Rimm, Eric
AU - Ascherio, Alberto
AU - Costenbader, Karen
AU - Karlson, Elizabeth
AU - Mucci, Lorelei
AU - Eliassen, A. Heather
AU - Zeleznik, Oana
AU - Miller, John
AU - Vavvas, Demetrios G.
AU - Kim, Ivana K.
AU - Silva, Rufino
AU - Miller, Joan
AU - Hu, Frank
AU - Willett, Walter
AU - Lasky-Su, Jessica
AU - Kraft, Peter
AU - Richards, J. Brent
AU - MacGregor, Stuart
AU - Husain, Deeba
AU - Liang, Liming
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/7/18
Y1 - 2023/7/18
N2 - 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.
AB - 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.
KW - AMD
KW - CLSA
KW - Canadian Longitudinal Study of Aging
KW - GWASs
KW - HCHS/SOL
KW - HPFS
KW - Health Professionals Follow Up Study
KW - Hispanic Community Health Study/Study of Latinos
KW - MR
KW - Mendelian randomization
KW - NHS
KW - Nurses’ Health Study
KW - UK Biobank
KW - age-related macular degeneration
KW - genome-wide association studies
KW - genomics
KW - metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85165277682&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85165277682&partnerID=8YFLogxK
U2 - 10.1016/j.xcrm.2023.101085
DO - 10.1016/j.xcrm.2023.101085
M3 - Article
C2 - 37348500
AN - SCOPUS:85165277682
SN - 2666-3791
VL - 4
JO - Cell Reports Medicine
JF - Cell Reports Medicine
IS - 7
M1 - 101085
ER -