The genetic landscape of neuro-related proteins in human plasma

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. 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 and Xia Shen ()
Additional contact information
Linda Repetto: Sun Yat-sen University
Jiantao Chen: Sun Yat-sen University
Zhijian Yang: Sun Yat-sen University
Ranran Zhai: Sun Yat-sen University
Paul R. H. J. Timmers: University of Edinburgh
Xiao Feng: Fudan University
Ting Li: Sun Yat-sen University
Yue Yao: Fudan University
Denis Maslov: Lomonosov Moscow State University
Anna Timoshchuk: Lomonosov Moscow State University
Fengyu Tu: Sun Yat-sen University
Emma L. Twait: University Medical Center Utrecht and Utrecht University
Sebastian May-Wilson: University of Edinburgh
Marisa D. Muckian: University of Edinburgh
Bram P. Prins: University of Cambridge
Grace Png: Helmholtz Zentrum München—German Research Center for Environmental Health
Charles Kooperberg: Fred Hutchinson Cancer Center
Åsa Johansson: Uppsala University
Robert F. Hillary: The University of Edinburgh
Eleanor Wheeler: University of Cambridge School of Clinical Medicine
Lu Pan: Karolinska Institutet
Yazhou He: Sichuan University
Sofia Klasson: University of Gothenburg
Shahzad Ahmad: Erasmus MC
James E. Peters: Imperial College London
Arthur Gilly: Helmholtz Zentrum München—German Research Center for Environmental Health
Maria Karaleftheri: Echinos Medical Centre
Emmanouil Tsafantakis: Anogia Medical Centre
Jeffrey Haessler: Fred Hutchinson Cancer Center
Ulf Gyllensten: Uppsala University
Sarah E. Harris: University of Edinburgh
Nicholas J. Wareham: University of Cambridge School of Clinical Medicine
Andreas Göteson: The Sahlgrenska Academy at the University of Gothenburg
Cecilia Lagging: University of Gothenburg
Mohammad Arfan Ikram: Erasmus MC
Cornelia M. Duijn: Erasmus MC
Christina Jern: University of Gothenburg
Mikael Landén: Karolinska Institutet
Claudia Langenberg: University of Cambridge School of Clinical Medicine
Ian J. Deary: University of Edinburgh
Riccardo E. Marioni: The University of Edinburgh
Stefan Enroth: Uppsala University
Alexander P. Reiner: University of Washington
George Dedoussis: Harokopio University of Athens
Eleftheria Zeggini: Helmholtz Zentrum München—German Research Center for Environmental Health
Sodbo Sharapov: Lomonosov Moscow State University
Yurii S. Aulchenko: Lomonosov Moscow State University
Adam S. Butterworth: University of Cambridge
Anders Mälarstig: Karolinska Institutet
James F. Wilson: University of Edinburgh
Pau Navarro: University of Edinburgh
Xia Shen: Sun Yat-sen University

Nature Human Behaviour, 2024, vol. 8, issue 11, 2222-2234

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41562-024-01963-z

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