1. Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders
- Author
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Linda Repetto, Jiantao Chen, Zhijian Yang, Ranran Zhai, Paul Timmers, Ting Li, Emma Twait, Sebastian May-Wilson, Marisa Muckian, Bram Prins, Grace Png, Charles Kooperberg, Åsa Johansson, Robert Hillary, Eleanor Wheeler, Lu Pan, Yazhou He, Sofia Klasson, Shahzad Ahmad, James Peters, Arthur Gilly, Maria Karaleftheri, Emmanouil Tsafantakis, Jeffrey Haessler, Ulf Gyllensten, Sarah Harris, Nicholas Wareham, Andreas Göteson, Cecilia Lagging, M. Arfan Ikram, Cornelia van Duijn, Christina Jern, Mikael Landén, Claudia Langenberg, Ian Deary, Riccardo Marioni, Stefan Enroth, Alexander Reiner, George Dedoussis, Eleftheria Zeggini, Adam Butterworth, Anders Mälarstig, James Wilson, Pau Navarro, and Xia Shen
- Abstract
Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related 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-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
- Published
- 2023