Pulse Brain · Growing Health Evidence Index
Peer-reviewed

Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics

Alvaro Barbeira, Scott Dickinson, Rodrigo Bonazzola, Jiamao Zheng, Heather E. Wheeler, Jason Torres, Eric S. Torstenson, Kaanan P. Shah, Tzintzuni Garcia, Todd L. Edwards, Eli A. Stahl, Laura M. Huckins, François Aguet, Kristin Ardlie, Beryl B. Cummings, Ellen Gelfand, Gad Getz, Kane Hadley, Robert E. Handsaker, Katherine Huang, Seva Kashin, Konrad J. Karczewski, Monkol Lek, Xiao Li, Daniel G. MacArthur, Jared L. Nedzel, Duyen T. Nguyen, Michael S. Noble, Ayellet V. Segrè, Casandra A. Trowbridge, Taru Tukiainen, Statistical Methods groups—Analysis Working Group, Nathan S. Abell, Brunilda Balliu, Ruth Barshir, Omer Basha, Alexis Battle, Gireesh K. Bogu, Andrew Brown, Christopher Brown, Stephane E. Castel, Lin Chen, Colby Chiang, Donald F. Conrad, Farhan N. Damani, Joe R. Davis, Olivier Delaneau, Emmanouil T. Dermitzakis, Barbara E. Engelhardt, Eleazar Eskin, Pedro G. Ferreira, Laure Frésard, Eric R. Gamazon, Diego Garrido-Martín, Ariel DH Gewirtz, Genna Gliner, Michael J. Gloudemans, Roderic Guigó, Ira M. Hall, Buhm Han, Yuan He, Farhad Hormozdiari, Cédric Howald, Brian Jo, Eun Yong Kang, Yungil Kim, Sarah Kim-Hellmuth, Tuuli Lappalainen, Gen Li, Xin Li, Boxiang Liu, Serghei Mangul, Mark I. McCarthy, Ian C. McDowell, Pejman Mohammadi, Jean Monlong, Stephen B. Montgomery, Manuel Muñoz-Aguirre, Anne W. Ndungu, Andrew B. Nobel, Meritxell Oliva, Halit Ongen, John Palowitch, Nikolaos Panousis, Panagiotis Papasaikas, YoSon Park, Princy Parsana, A. J. Payne, Christine B. Peterson, Jie Quan, Ferrán Reverter, Chiara Sabatti, Ashis Saha, Michael Sammeth, Alexandra J. Scott, Andrey A. Shabalin, Reza Sodaei, Matthew Stephens, Barbara E. Stranger, Benjamin J. Strober

Nature Communications · 2018

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Summary

Scalable, integrative methods to understand mechanisms that link genetic variants with phenotypes are needed. Here we derive a mathematical expression to compute PrediXcan (a gene mapping approach) results using summary data (S-PrediXcan) and show its accuracy and general robustness to misspecified reference sets. We apply this framework to 44 GTEx tissues and 100+ phenotypes from GWAS and meta-analysis studies, creating a growing public catalog of associations that seeks to capture the effects of gene expression variation on human phenotypes. Replication in an independent cohort is shown. Most of the associations are tissue specific, suggesting context specificity of the trait etiology. Colocalized significant associations in unexpected tissues underscore the need for an agnostic scanning

Source type
Peer-reviewed study
DOI
10.1038/s41467-018-03621-1
Catalogue ID
SNmois846h-9a82p5
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