ArticleCell reports. Medicine2023
Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration.
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Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 39 citations in OpenAlex.
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- Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms.Experimental eye research · 2025Review
- Metabolomic Characteristics of Aqueous Humor in Wet Age-Related Macular Degeneration and the Impact of Anti-VEGF Treatment.Investigative ophthalmology & visual science · 2025Article
- Serum metabolites and risk of aortic dissection: a two-sample Mendelian randomization study.Indian journal of thoracic and cardiovascular surgery · 2025Article
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Authors and funding
35 authors at 12 institutions in 5 countries.
Xikun HanDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: xikun_han@hsph.harvard.edu.
Ines LainsMassachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Jun LiDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jinglun LiDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Yiheng ChenLady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada; Department of Human Genetics, McGill University, Montréal, QC, Canada.
Bing YuDepartment of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Qibin QiDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA.
Eric BoerwinkleDepartment of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Robert KaplanDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA; Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Bharat ThyagarajanDepartment of Laboratory Medicine and Pathology, University of Minnesota Medical Center, Minneapolis, MN, USA.
Martha DaviglusInstitute for Minority Health Research, University of Illinois at Chicago, Chicago, IL, USA.
Charlotte E JoslinDepartment of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.
Jianwen CaiDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Marta Guasch-FerréDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Deirdre K TobiasDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Eric RimmDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Alberto AscherioDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Karen CostenbaderDivision of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Elizabeth KarlsonDivision of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Lorelei MucciDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
A Heather EliassenDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Oana ZeleznikChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
John MillerMassachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Demetrios G VavvasRetina Service, Ines and Fredrick Yeatts Retinal Research Laboratory, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Ivana K KimMassachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Rufino SilvaOphthalmology Unit, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal; University Clinic of Ophthalmology, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
Joan MillerMassachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Frank HuDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Walter WillettDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jessica Lasky-SuSystems Genetics and Genomics Unit, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Peter KraftDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
J Brent RichardsLady Davis Institute, Jewish General Hospital, McGill University, Montréal, QC, Canada; Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, McGill University, Montréal, QC, Canada; Department of Twin Research, King's College London, London, UK; Five Prime Sciences Inc, Montréal, QC, Canada.
Stuart MacGregorStatistical Genetics Lab, QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia.
Deeba HusainMassachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA. Electronic address: deeba_husain@meei.harvard.edu.
Liming LiangDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Program in Genetic Epidemiology and Statistical Genetics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: lliang@hsph.harvard.edu.
Harvard University · USBrigham and Women's Hospital · USMassachusetts Eye and Ear Infirmary · USAlbert Einstein College of Medicine · USThe University of Texas Health Science Center at Houston · USUniversity of Illinois Chicago · USHospitais da Universidade de Coimbra · PTJewish General Hospital · CAKing's College London · GBQIMR Berghofer Medical Research Institute · AUUniversity of Minnesota Medical Center · USUniversity of North Carolina at Chapel Hill · US
Funding
Life Course Cancer Epidemiology Cohort in WomenU01CA176726 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 2018 to 2025
$22.4MLong Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3MCancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0MPilot Program CoreP30ES027792 · NIEHS · UNIVERSITY OF CHICAGO · PI Briseis A Aschebrook-Kilfoy · 2017 to 2026
$13.6MPremonopausal Hormone Levels and Risk of Breast CancerR01CA067262 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HANKINSON, SUSAN E · 2002 to 2011
$11.9MBIOCHEMICAL MARKERS IN THE NURSES'HEALTH STUDY COHORTR01CA049449 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI HANKINSON, SUSAN E · 1989 to 2008
$11.3MNovel Biomarkers and Prediction Models for Rheumatoid ArthritisR01AR049880 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI COSTENBADER, KAREN H, KARLSON, ELIZABETH W · 2003 to 2018
$8.7MMetabolomics a Novel Tool for Investigating the Pathogenesis of Age-related Macular DegenerationR01EY030088 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Deeba Husain · 2020 to 2026
$3.5MChronic Inflammation and Type 2 Diabetes: A Multi-omics ApproachR00DK122128 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI LI, JUN · 2022 to 2024
$723kHISPANIC COMMUNITY HEALTH STUDY-268065233N01HC065233 · HC · COORDINATING CENTER · PI CHAMBLESS, LLOYD E · 2006 to 2006
–NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA067262NCI NIH HHS U01 CA167552NCI NIH HHS U01 CA176726NCI NIH HHS UM1 CA186107NEI NIH HHS R01 EY030088NHLBI NIH HHS N01 HC065233NHLBI NIH HHS N01 HC065234NHLBI NIH HHS N01 HC065235NHLBI NIH HHS N01 HC065236NHLBI NIH HHS N01 HC065237NIAMS NIH HHS R01 AR049880NIDDK NIH HHS R00 DK122128NIEHS NIH HHS P30 ES027792Wellcome Trust
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.
Indexed as
Genome-Wide Association StudyMacular DegenerationAgedBayes TheoremHumansMetabolomeMetabolomicsage-related macular degenerationAMDCanadian Longitudinal Study of AgingCLSAgenome-wide association studiesgenomicsGWASsHCHS/SOLHealth Professionals Follow Up StudyHispanic Community Health Study/Study of LatinosHPFSMendelian randomizationmetabolomicsMRNHSNurses’ Health StudyUK Biobank
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