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Genetic mechanisms of 184 neuro-related proteins in human plasma

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-reia...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9949195/
https://www.ncbi.nlm.nih.gov/pubmed/36824751
http://dx.doi.org/10.1101/2023.02.10.23285650
Descripción
Sumario: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.