Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints
Abstract Metabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Here, we perform two-sample Mendelian randomization to systematically infer the potential causal effects of 1099 plasma metabolites measured in 6136 Finnish men from the METSIM study...
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| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58129-2 |
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| author | Xianyong Yin Jack Li Debraj Bose Jeffrey Okamoto Annie Kwon Anne U. Jackson Lilian Fernandes Silva Anniina Oravilahti Xiaomeng Chu Heather M. Stringham Lei Liu Ruyi Peng Zhijie Xia Samuli Ripatti Mark Daly Aarno Palotie Laura J. Scott Charles F. Burant Eric B. Fauman Xiaoquan Wen Michael Boehnke Markku Laakso Jean Morrison |
| author_facet | Xianyong Yin Jack Li Debraj Bose Jeffrey Okamoto Annie Kwon Anne U. Jackson Lilian Fernandes Silva Anniina Oravilahti Xiaomeng Chu Heather M. Stringham Lei Liu Ruyi Peng Zhijie Xia Samuli Ripatti Mark Daly Aarno Palotie Laura J. Scott Charles F. Burant Eric B. Fauman Xiaoquan Wen Michael Boehnke Markku Laakso Jean Morrison |
| author_sort | Xianyong Yin |
| collection | DOAJ |
| description | Abstract Metabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Here, we perform two-sample Mendelian randomization to systematically infer the potential causal effects of 1099 plasma metabolites measured in 6136 Finnish men from the METSIM study on risk of 2099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen. We find evidence for 282 putative causal effects of 70 metabolites on 183 disease endpoints. We also identify 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 putative causal effect of N6,N6-dimethyllysine on anxious personality disorder. |
| format | Article |
| id | doaj-art-e7b0e132fca54462a0771c858f53f363 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e7b0e132fca54462a0771c858f53f3632025-08-20T02:49:35ZengNature PortfolioNature Communications2041-17232025-03-0116111010.1038/s41467-025-58129-2Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpointsXianyong Yin0Jack Li1Debraj Bose2Jeffrey Okamoto3Annie Kwon4Anne U. Jackson5Lilian Fernandes Silva6Anniina Oravilahti7Xiaomeng Chu8Heather M. Stringham9Lei Liu10Ruyi Peng11Zhijie Xia12Samuli Ripatti13Mark Daly14Aarno Palotie15Laura J. Scott16Charles F. Burant17Eric B. Fauman18Xiaoquan Wen19Michael Boehnke20Markku Laakso21Jean Morrison22Department 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 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 HospitalInstitute 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 Epidemiology, School of Public Health, Nanjing Medical UniversityDepartment of Epidemiology, School of Public Health, Nanjing Medical UniversityDepartment of Epidemiology, School of Public Health, Nanjing Medical UniversityInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of HelsinkiInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of HelsinkiInstitute for Molecular Medicine Finland, FIMM, HiLIFE, University of HelsinkiDepartment of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthDepartment of Internal Medicine, University of MichiganInternal Medicine Research Unit, Pfizer Worldwide Research, Development and MedicalDepartment 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 Biostatistics and Center for Statistical Genetics, University of Michigan School of Public HealthAbstract Metabolites are small molecules that are useful for estimating disease risk and elucidating disease biology. Here, we perform two-sample Mendelian randomization to systematically infer the potential causal effects of 1099 plasma metabolites measured in 6136 Finnish men from the METSIM study on risk of 2099 binary disease endpoints measured in 309,154 Finnish individuals from FinnGen. We find evidence for 282 putative causal effects of 70 metabolites on 183 disease endpoints. We also identify 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 putative causal effect of N6,N6-dimethyllysine on anxious personality disorder.https://doi.org/10.1038/s41467-025-58129-2 |
| spellingShingle | Xianyong Yin Jack Li Debraj Bose Jeffrey Okamoto Annie Kwon Anne U. Jackson Lilian Fernandes Silva Anniina Oravilahti Xiaomeng Chu Heather M. Stringham Lei Liu Ruyi Peng Zhijie Xia Samuli Ripatti Mark Daly Aarno Palotie Laura J. Scott Charles F. Burant Eric B. Fauman Xiaoquan Wen Michael Boehnke Markku Laakso Jean Morrison Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints Nature Communications |
| title | Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints |
| title_full | Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints |
| title_fullStr | Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints |
| title_full_unstemmed | Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints |
| title_short | Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints |
| title_sort | assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints |
| url | https://doi.org/10.1038/s41467-025-58129-2 |
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