Linda Repetto, Jiantao Chen, Zhijian Yang, Ranran Zhai, Paul R. H. J. Timmers, Xiao Feng, Ting Li, Yue Yao, Denis Maslov, Anna Timoshchuk, Fengyu Tu, Emma L. Twait, Sebastian May-Wilson, Marisa D. Muckian, Bram P. Prins, Grace Png, Charles Kooperberg, Åsa Johansson, Robert F. Hillary, Eleanor Wheeler, Lu Pan, Yazhou He, Sofia Klasson, Shahzad Ahmad, James E. Peters, Arthur Gilly, Maria Karaleftheri, Emmanouil Tsafantakis, Jeffrey Haessler, Ulf Gyllensten, Sarah E. Harris, Nicholas J. Wareham, Andreas Göteson, Cecilia Lagging, Mohammad Arfan Ikram, Cornelia M. van Duijn, Christina Jern, Mikael Landén, Claudia Langenberg, Ian J. Deary, Riccardo E. Marioni, Stefan Enroth, Alexander P. Reiner, George Dedoussis, Eleftheria Zeggini, Sodbo Sharapov, Yurii S. Aulchenko, Adam S. Butterworth, Anders Mälarstig, James F. Wilson, Pau Navarro, Xia Shen
{"title":"人体血浆中神经相关蛋白的遗传图谱","authors":"Linda Repetto, Jiantao Chen, Zhijian Yang, Ranran Zhai, Paul R. H. J. Timmers, Xiao Feng, Ting Li, Yue Yao, Denis Maslov, Anna Timoshchuk, Fengyu Tu, Emma L. Twait, Sebastian May-Wilson, Marisa D. Muckian, Bram P. Prins, Grace Png, Charles Kooperberg, Åsa Johansson, Robert F. Hillary, Eleanor Wheeler, Lu Pan, Yazhou He, Sofia Klasson, Shahzad Ahmad, James E. Peters, Arthur Gilly, Maria Karaleftheri, Emmanouil Tsafantakis, Jeffrey Haessler, Ulf Gyllensten, Sarah E. Harris, Nicholas J. Wareham, Andreas Göteson, Cecilia Lagging, Mohammad Arfan Ikram, Cornelia M. van Duijn, Christina Jern, Mikael Landén, Claudia Langenberg, Ian J. Deary, Riccardo E. Marioni, Stefan Enroth, Alexander P. Reiner, George Dedoussis, Eleftheria Zeggini, Sodbo Sharapov, Yurii S. Aulchenko, Adam S. Butterworth, Anders Mälarstig, James F. Wilson, Pau Navarro, Xia Shen","doi":"10.1038/s41562-024-01963-z","DOIUrl":null,"url":null,"abstract":"<p>Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 <i>cis</i>-regulatory protein quantitative trait loci (<i>cis</i>-pQTL) and 164 <i>trans</i>-pQTL. The mapped pQTL capture on average 50% of each protein’s heritability. At the <i>cis</i>-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.</p>","PeriodicalId":19074,"journal":{"name":"Nature Human Behaviour","volume":null,"pages":null},"PeriodicalIF":21.4000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The genetic landscape of neuro-related proteins in human plasma\",\"authors\":\"Linda Repetto, Jiantao Chen, Zhijian Yang, Ranran Zhai, Paul R. H. J. Timmers, Xiao Feng, Ting Li, Yue Yao, Denis Maslov, Anna Timoshchuk, Fengyu Tu, Emma L. Twait, Sebastian May-Wilson, Marisa D. Muckian, Bram P. Prins, Grace Png, Charles Kooperberg, Åsa Johansson, Robert F. Hillary, Eleanor Wheeler, Lu Pan, Yazhou He, Sofia Klasson, Shahzad Ahmad, James E. Peters, Arthur Gilly, Maria Karaleftheri, Emmanouil Tsafantakis, Jeffrey Haessler, Ulf Gyllensten, Sarah E. Harris, Nicholas J. Wareham, Andreas Göteson, Cecilia Lagging, Mohammad Arfan Ikram, Cornelia M. van Duijn, Christina Jern, Mikael Landén, Claudia Langenberg, Ian J. Deary, Riccardo E. Marioni, Stefan Enroth, Alexander P. Reiner, George Dedoussis, Eleftheria Zeggini, Sodbo Sharapov, Yurii S. Aulchenko, Adam S. Butterworth, Anders Mälarstig, James F. Wilson, Pau Navarro, Xia Shen\",\"doi\":\"10.1038/s41562-024-01963-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 <i>cis</i>-regulatory protein quantitative trait loci (<i>cis</i>-pQTL) and 164 <i>trans</i>-pQTL. The mapped pQTL capture on average 50% of each protein’s heritability. At the <i>cis</i>-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. 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The genetic landscape of neuro-related proteins in human plasma
Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein’s heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.
期刊介绍：
Nature Human Behaviour is a journal that focuses on publishing research of outstanding significance into any aspect of human behavior.The research can cover various areas such as psychological, biological, and social bases of human behavior.It also includes the study of origins, development, and disorders related to human behavior.The primary aim of the journal is to increase the visibility of research in the field and enhance its societal reach and impact.
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