Metabolome-wide Mendelian randomization characterizes heterogeneous and shared causal effects of metabolites on human health
Metabolome-wide Mendelian randomization characterizes heterogeneous and shared causal effects of metabolites on human health
Summary Metabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Nevertheless, their causal effects on human diseases have not been evaluated comprehensively. We performed two-sample Mendelian randomization to systematically infer the causal effects of 1,099 plasma metabolites measured in 6,136 Finnish men from the METSIM study on risk of 2,099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen. We identified evidence for 282 causal effects of 70 metabolites on 183 disease endpoints (FDR<1%). We found 25 metabolites with potential causal effects across multiple disease domains, including ascorbic acid 2-sulfate affecting 26 disease endpoints in 12 disease domains. Our study suggests that N-acetyl-2-aminooctanoate and glycocholenate sulfate affect risk of atrial fibrillation through two distinct metabolic pathways and that N-methylpipecolate may mediate the causal effect of N6, N6-dimethyllysine on anxious personality disorder. This study highlights the broad causal impact of plasma metabolites and widespread metabolic connections across diseases.
Daly Mark、Wen Xiaoquan、Boehnke Michael、Jackson Anne U.、Silva Lilian Fernandes、Yin Xianyong、Bose Debraj、Li Jack、Okamoto Jeffrey、Kwon Annie、Palotie Aarno、Morrison Jean、Oravilahti Anniina、Burant Charles F.、Laakso Markku、Scott Laura J.、Stringham Heather M.、Ripatti Samuli、Fauman Eric B.
Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki||Department of Public Health, University of Helsinki||Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology, and Department of Psychiatry, Massachusetts General HospitalDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University HospitalDepartment of Epidemiology, School of Public Health, Nanjing Medical UniversityDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki||Department of Public Health, University of Helsinki||Analytic and Translational Genetics Unit, Department of Medicine, Department of Neurology, and Department of Psychiatry, Massachusetts General HospitalDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University HospitalDepartment of Internal Medicine, University of MichiganInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University HospitalDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki||Department of Public Health, University of Helsinki||Broad Institute of MIT & HarvardInternal Medicine Research Unit, Pfizer Worldwide Research, Development and Medical
医学研究方法基础医学生物化学
Daly Mark,Wen Xiaoquan,Boehnke Michael,Jackson Anne U.,Silva Lilian Fernandes,Yin Xianyong,Bose Debraj,Li Jack,Okamoto Jeffrey,Kwon Annie,Palotie Aarno,Morrison Jean,Oravilahti Anniina,Burant Charles F.,Laakso Markku,Scott Laura J.,Stringham Heather M.,Ripatti Samuli,Fauman Eric B..Metabolome-wide Mendelian randomization characterizes heterogeneous and shared causal effects of metabolites on human health[EB/OL].(2025-03-28)[2025-04-30].https://www.medrxiv.org/content/10.1101/2023.06.26.23291721.点此复制
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