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Repetto, L.* ; Chen, J.* ; Yang, Z.* ; Zhai, R.* ; Timmers, P.R.H.J.* ; Feng, X.* ; Li, T.* ; Yao, Y.* ; Maslov, D.* ; Timoshchuk, A.* ; Tu, F.* ; Twait, E.L.* ; May-Wilson, S.* ; Muckian, M.D.* ; Prins, B.P.* ; Png, G. ; Kooperberg, C.* ; Johansson, Å* ; Hillary, R.F.* ; Wheeler, E.* ; Pan, L.* ; He, Y.* ; Klasson, S.* ; Ahmad, S.* ; Peters, J.E.* ; Gilly, A. ; Karaleftheri, M.* ; Tsafantakis, E.* ; Haessler, J.* ; Gyllensten, U.* ; Harris, S.E.* ; Wareham, N.J.* ; Göteson, A.* ; Lagging, C.* ; Ikram, M.A.* ; van Duijn, C.M.* ; Jern, C.* ; Landén, M.* ; Langenberg, C.* ; Deary, I.J.* ; Marioni, R.E.* ; Enroth, S.* ; Reiner, A.P.* ; Dedoussis, G.* ; Zeggini, E. ; Sharapov, S.* ; Aulchenko, Y.S.* ; Butterworth, A.S.* ; Mälarstig, A.* ; Wilson, J.F.* ; Navarro, P.* ; Shen, X.*

The genetic landscape of neuro-related proteins in human plasma.

Nat. Hum. Behav. 8, 2222-2234 (2024)
Postprint DOI PMC
Open Access Green
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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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Association; Loci; Atlas; Risk
ISSN (print) / ISBN 2397-3374
e-ISSN 2397-3374
Journal Nature human behaviour
Quellenangaben Volume: 8, Issue: 11, Pages: 2222-2234 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Translational Genomics (ITG)
Grants China Postdoctoral Science Foundation
National Key Research and Development Program grant
National Natural Science Foundation of China (NSFC)
Natural Science Foundation of Guangdong Province
Swedish Research Council (Vetenskapsrdet)
Medical Research Council Human Genetics Unit Program grant 'Quantitative Traits in Health and Disease'
Research Program at the Moscow State University (MSU) Institute for Artificial Intelligence
National Natural Science Foundation of China (National Science Foundation of China)