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Genetic mechanisms of 184 neuro-related proteins in human plasma.
Repetto, Linda; Chen, Jiantao; Yang, Zhijian; Zhai, Ranran; Timmers, Paul R H J; Li, Ting; 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; Butterworth, Adam S; Mälarstig, Anders; Wilson, James F; Navarro, Pau; Shen, Xia.
Afiliação
  • Repetto L; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Chen J; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
  • Yang Z; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Zhai R; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
  • Timmers PRHJ; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Li T; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Twait EL; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
  • May-Wilson S; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Muckian MD; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Prins BP; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
  • Png G; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • Kooperberg C; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Johansson Å; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Hillary RF; MRC Human Genetics Unit, MRC Institute of Genetics Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Wheeler E; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
  • Pan L; Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), Fudan University, Guangzhou, China.
  • He Y; Biostatistics Group, School of Life Sciences, Sun Yat-sen University, Guangzhou, China.
  • Klasson S; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht and Utrecht University, Utrecht, Netherlands.
  • Ahmad S; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Peters JE; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Gilly A; BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
  • Karaleftheri M; Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  • Tsafantakis E; Technical University of Munich (TUM), School of Medicine, 81675 Munich, Germany.
  • Haessler J; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle USA.
  • Gyllensten U; Dept. Immunology, Genetics and Pathology, Science for life laboratory, Uppsala University, Sweden.
  • Harris SE; Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, The University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom.
  • Wareham NJ; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
  • Göteson A; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Lagging C; Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.
  • Ikram MA; Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • van Duijn CM; Department of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.
  • Jern C; Department of Immunology and Inflammation, Faculty of Medicine, Imperial College London, London, United Kingdom.
  • Landén M; Institute of Translational Genomics, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.
  • Langenberg C; Echinos Medical Centre, Echinos, Greece.
  • Deary IJ; Anogia Medical Centre, Anogia, Greece.
  • Marioni RE; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle USA.
  • Enroth S; Dept. Immunology, Genetics and Pathology, Science for life laboratory, Uppsala University, Sweden.
  • Reiner AP; Lothian Birth Cohorts, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
  • Dedoussis G; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
  • Zeggini E; Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Butterworth AS; Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Mälarstig A; Region Västra Götaland, Sahlgrenska University Hospital, Department of Clinical Genetics and Genomics, Gothenburg, Sweden.
  • Wilson JF; Department of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.
  • Navarro P; Department of Epidemiology, ErasmusMC, Rotterdam, The Netherlands.
  • Shen X; Institute of Biomedicine, Department of Laboratory Medicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
medRxiv ; 2023 Feb 14.
Article em En | MEDLINE | ID: mdl-36824751
Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-reiated proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-reiated traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2023 Tipo de documento: Article