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The genetic landscape of neuro-related proteins in human plasma.
Repetto, Linda; Chen, Jiantao; Yang, Zhijian; Zhai, Ranran; Timmers, Paul R H J; Feng, Xiao; Li, Ting; Yao, Yue; Maslov, Denis; Timoshchuk, Anna; Tu, Fengyu; Twait, Emma L; May-Wilson, Sebastian; Muckian, Marisa D; Prins, Bram P; Png, Grace; Kooperberg, Charles; Johansson, Åsa; Hillary, Robert F; Wheeler, Eleanor; Pan, Lu; He, Yazhou; Klasson, Sofia; Ahmad, Shahzad; Peters, James E; Gilly, Arthur; Karaleftheri, Maria; Tsafantakis, Emmanouil; Haessler, Jeffrey; Gyllensten, Ulf; Harris, Sarah E; Wareham, Nicholas J; Göteson, Andreas; Lagging, Cecilia; Ikram, Mohammad Arfan; van Duijn, Cornelia M; Jern, Christina; Landén, Mikael; Langenberg, Claudia; Deary, Ian J; Marioni, Riccardo E; Enroth, Stefan; Reiner, Alexander P; Dedoussis, George; Zeggini, Eleftheria; Sharapov, Sodbo; Aulchenko, Yurii S; Butterworth, Adam S; Mälarstig, Anders; Wilson, James F.
Afiliação
  • Repetto L; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Chen J; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Yang Z; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Zhai R; Health Data Science Centre, Fondazione Human Technopole, Milan, Italy.
  • Timmers PRHJ; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Feng X; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Li T; State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China.
  • Yao Y; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Maslov D; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Timoshchuk A; State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China.
  • Tu F; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Twait EL; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • May-Wilson S; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Muckian MD; State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China.
  • Prins BP; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Png G; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Kooperberg C; MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Johansson Å; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Hillary RF; State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China.
  • Wheeler E; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Pan L; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • He Y; State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China.
  • Klasson S; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Ahmad S; State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Shanghai, China.
  • Peters JE; MSU Institute for Artificial Intelligence, Lomonosov Moscow State University, Moscow, Russia.
  • Gilly A; MSU Institute for Artificial Intelligence, Lomonosov Moscow State University, Moscow, Russia.
  • Karaleftheri M; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Tsafantakis E; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht and Utrecht University, Utrecht, Netherlands.
  • Haessler J; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Gyllensten U; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Harris SE; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Wareham NJ; Institute of Translational Genomics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Göteson A; Technical University of Munich (TUM), TUM School of Medicine and Health, Munich, Germany.
  • Lagging C; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Ikram MA; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • van Duijn CM; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh, UK.
  • Jern C; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
  • Landén M; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Langenberg C; Department of Epidemiology and Medical Statistics, Division of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • Deary IJ; Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Marioni RE; Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
  • Enroth S; Department of Immunology and Inflammation, Faculty of Medicine, Imperial College London, London, UK.
  • Reiner AP; Institute of Translational Genomics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Dedoussis G; Echinos Medical Centre, Echinos, Greece.
  • Zeggini E; Anogia Medical Centre, Anogia, Greece.
  • Sharapov S; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Aulchenko YS; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Butterworth AS; Lothian Birth Cohorts, University of Edinburgh, Edinburgh, UK.
  • Mälarstig A; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
  • Wilson JF; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Nat Hum Behav ; 2024 Aug 29.
Article em En | MEDLINE | ID: mdl-39210026
ABSTRACT
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article