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Repetto L, Chen J, Yang Z, Zhai R, Timmers PRHJ, Li T, Twait EL, May-Wilson S, Muckian MD, Prins BP, Png G, Kooperberg C, Johansson Å, Hillary RF, Wheeler E, Pan L, He Y, Klasson S, Ahmad S, Peters JE, Gilly A, Karaleftheri M, Tsafantakis E, Haessler J, Gyllensten U, Harris SE, Wareham NJ, Göteson A, Lagging C, Ikram MA, van Duijn CM, Jern C, Landén M, Langenberg C, Deary IJ, Marioni RE, Enroth S, Reiner AP, Dedoussis G, Zeggini E, Butterworth AS, Mälarstig A, Wilson JF, Navarro P, Shen X
medRxiv - (-) - [2023-02-14; online 2023-02-14]
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.
PubMed 36824751
DOI 10.1101/2023.02.10.23285650
Crossref 10.1101/2023.02.10.23285650
pmc: PMC9949195
pii: 2023.02.10.23285650