{"title":"汉族慢性疾病血清代谢组遗传定位。","authors":"Chunxiao Cheng, Fengzhe Xu, Xiong-Fei Pan, Cheng Wang, Jiayao Fan, Yunhaonan Yang, Yuanjiao Liu, Lingyun Sun, Xiaojuan Liu, Yue Xu, Yuan Zhou, Congmei Xiao, Wanglong Gou, Zelei Miao, Jiaying Yuan, Luqi Shen, Yuanqing Fu, Xiaohui Sun, Yimin Zhu, Yuming Chen, An Pan, Dan Zhou, Ju-Sheng Zheng","doi":"10.1016/j.xgen.2024.100743","DOIUrl":null,"url":null,"abstract":"<p><p>Serum metabolites are potential regulators for chronic diseases. To explore the genetic regulation of metabolites and their roles in chronic diseases, we quantified 2,759 serum metabolites and performed genome-wide association studies (GWASs) among Han Chinese individuals. We identified 184 study-wide significant (p < 1.81 × 10<sup>-11</sup>) metabolite quantitative trait loci (metaboQTLs), 88.59% (163) of which were novel. Notably, we identified Asian-ancestry-specific metaboQTLs, including the SNP rs2296651 for taurocholic acid and taurochenodesoxycholic acid. Leveraging the GWAS for 37 clinical traits from East Asians, Mendelian randomization analyses identified 906 potential causal relationships between metabolites and clinical traits, including 27 for type 2 diabetes and 38 for coronary artery disease. Integrating genetic regulation of the transcriptome and proteome revealed putative regulators of several metabolites. In summary, we depict a landscape of the genetic architecture of the serum metabolome among Han Chinese and provide insights into the role of serum metabolites in chronic diseases.</p>","PeriodicalId":72539,"journal":{"name":"Cell genomics","volume":" ","pages":"100743"},"PeriodicalIF":11.1000,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic mapping of serum metabolome to chronic diseases among Han Chinese.\",\"authors\":\"Chunxiao Cheng, Fengzhe Xu, Xiong-Fei Pan, Cheng Wang, Jiayao Fan, Yunhaonan Yang, Yuanjiao Liu, Lingyun Sun, Xiaojuan Liu, Yue Xu, Yuan Zhou, Congmei Xiao, Wanglong Gou, Zelei Miao, Jiaying Yuan, Luqi Shen, Yuanqing Fu, Xiaohui Sun, Yimin Zhu, Yuming Chen, An Pan, Dan Zhou, Ju-Sheng Zheng\",\"doi\":\"10.1016/j.xgen.2024.100743\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Serum metabolites are potential regulators for chronic diseases. To explore the genetic regulation of metabolites and their roles in chronic diseases, we quantified 2,759 serum metabolites and performed genome-wide association studies (GWASs) among Han Chinese individuals. We identified 184 study-wide significant (p < 1.81 × 10<sup>-11</sup>) metabolite quantitative trait loci (metaboQTLs), 88.59% (163) of which were novel. Notably, we identified Asian-ancestry-specific metaboQTLs, including the SNP rs2296651 for taurocholic acid and taurochenodesoxycholic acid. Leveraging the GWAS for 37 clinical traits from East Asians, Mendelian randomization analyses identified 906 potential causal relationships between metabolites and clinical traits, including 27 for type 2 diabetes and 38 for coronary artery disease. Integrating genetic regulation of the transcriptome and proteome revealed putative regulators of several metabolites. In summary, we depict a landscape of the genetic architecture of the serum metabolome among Han Chinese and provide insights into the role of serum metabolites in chronic diseases.</p>\",\"PeriodicalId\":72539,\"journal\":{\"name\":\"Cell genomics\",\"volume\":\" \",\"pages\":\"100743\"},\"PeriodicalIF\":11.1000,\"publicationDate\":\"2025-02-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell genomics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xgen.2024.100743\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/20 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell genomics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.xgen.2024.100743","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Genetic mapping of serum metabolome to chronic diseases among Han Chinese.
Serum metabolites are potential regulators for chronic diseases. To explore the genetic regulation of metabolites and their roles in chronic diseases, we quantified 2,759 serum metabolites and performed genome-wide association studies (GWASs) among Han Chinese individuals. We identified 184 study-wide significant (p < 1.81 × 10-11) metabolite quantitative trait loci (metaboQTLs), 88.59% (163) of which were novel. Notably, we identified Asian-ancestry-specific metaboQTLs, including the SNP rs2296651 for taurocholic acid and taurochenodesoxycholic acid. Leveraging the GWAS for 37 clinical traits from East Asians, Mendelian randomization analyses identified 906 potential causal relationships between metabolites and clinical traits, including 27 for type 2 diabetes and 38 for coronary artery disease. Integrating genetic regulation of the transcriptome and proteome revealed putative regulators of several metabolites. In summary, we depict a landscape of the genetic architecture of the serum metabolome among Han Chinese and provide insights into the role of serum metabolites in chronic diseases.
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