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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration. / Han, Xikun; Lains, Ines; 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.

In: Cell Reports Medicine, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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 2023, 'Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration', Cell Reports Medicine. https://doi.org/10.1016/j.xcrm.2023.101085

APA

Han, X., Lains, I., Li, J., Li, J., Chen, Y., Yu, B., Qi, Q., Boerwinkle, E., Kaplan, R., Thyagarajan, B., Daviglus, M., Joslin, C. E., Cai, J., Guasch-Ferré, M., Tobias, D. K., Rimm, E., Ascherio, A., Costenbader, K., Karlson, E., ... Liang, L. (Accepted/In press). Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration. Cell Reports Medicine, [101085]. https://doi.org/10.1016/j.xcrm.2023.101085

Vancouver

Han X, Lains I, Li J, Li J, Chen Y, Yu B et al. Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration. Cell Reports Medicine. 2023. 101085. https://doi.org/10.1016/j.xcrm.2023.101085

Author

Han, Xikun ; Lains, Ines ; 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. / Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration. In: Cell Reports Medicine. 2023.

Bibtex

@article{38a6757ddb31408e973b6e6a9bf124e3,
title = "Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration",
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.",
author = "Xikun Han and Ines Lains and Jun Li and Jinglun Li and Yiheng Chen and Bing Yu and Qibin Qi and Eric Boerwinkle and Robert Kaplan and Bharat Thyagarajan and Martha Daviglus and Joslin, {Charlotte E} and Jianwen Cai and Marta Guasch-Ferr{\'e} and Tobias, {Deirdre K} and Eric Rimm and Alberto Ascherio and Karen Costenbader and Elizabeth Karlson and Lorelei Mucci and Eliassen, {A Heather} and Oana Zeleznik and John Miller and Vavvas, {Demetrios G} and Kim, {Ivana K} and Rufino Silva and Joan Miller and Frank Hu and Walter Willett and Jessica Lasky-Su and Peter Kraft and Richards, {J Brent} and Stuart MacGregor and Deeba Husain and Liming Liang",
note = "Copyright {\textcopyright} 2023 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2023",
doi = "10.1016/j.xcrm.2023.101085",
language = "English",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",

}

RIS

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 - Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2023

Y1 - 2023

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.

U2 - 10.1016/j.xcrm.2023.101085

DO - 10.1016/j.xcrm.2023.101085

M3 - Journal article

C2 - 37348500

JO - Cell Reports Medicine

JF - Cell Reports Medicine

SN - 2666-3791

M1 - 101085

ER -

ID: 358111737