作者
Alvaro N Barbeira, Scott P Dickinson, Rodrigo Bonazzola, Jiamao Zheng, Heather E Wheeler, Jason M Torres, Eric S Torstenson, Kaanan P Shah, Tzintzuni Garcia, Todd L Edwards, Eli A Stahl, Laura M Huckins, NIH Common Fund Nierras Concepcion R. 87, NIH/NCI Branton Philip A. 88 Carithers Latarsha J. 88 89 Guan Ping 88 Moore Helen M. 88 Rao Abhi 88 Vaught Jimmie B. 88, NIH/NHGrI Gould Sarah E. 90 Lockart Nicole C. 90 Martin Casey 90 Struewing Jeffery P. 90 Volpi Simona 90, NIH/NIMH Addington Anjene M. 91 Koester Susan E. 91, NIH/NIDA Little A. Roger 92, Biospecimen Collection Source Site—rPCI Bridge Jason 99 Foster Barbara A. 100 Gillard Bryan M. 100 Karasik Ellen 100 Kumar Rachna 100 Miklos Mark 99 Moser Michael T. 100, Biospecimen Core resource—VArI Jewell Scott D. 101 Montroy Robert G. 101 Rohrer Daniel C. 101 Valley Dana R. 101, Brain Bank repository—University of Miami Brain Endowment Bank Davis David A. 102 Mash Deborah C. 102, ELSI Study Barker Laura K. 106 Mosavel Maghboeba 107 Siminoff Laura A. 106 Traino Heather M. 106, Genome Browser Data Integration & Visualization—EBI Flicek Paul 108 Juettemann Thomas 108 Ruffier Magali 108 Sheppard Dan 108 Taylor Kieron 108 Trevanion Stephen J. 108 Zerbino Daniel R. 108
发表日期
2018/5/8
期刊
Nature communications
卷号
9
期号
1
页码范围
1825
出版商
Nature Publishing Group UK
简介
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 of multiple contexts to improve our ability to detect causal regulatory mechanisms. Monogenic disease …
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AN Barbeira, SP Dickinson, R Bonazzola, J Zheng… - Nature communications, 2018