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<p>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.</p>

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Assessing the potential causal effects of 1099 plasma metabolites on 2099 binary disease endpoints

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月28日

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  • 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

摘要

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.