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Title: Integrative genomics identifies new genes associated with severe COPD and emphysema
Authors: Phuwanat Sakornsakolpat
Jarrett D. Morrow
Peter J. Castaldi
Craig P. Hersh
Yohan Bossé
Edwin K. Silverman
Ani Manichaikul
Michael H. Cho
Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval
University of Virginia
Brigham and Women's Hospital
Faculty of Medicine, Siriraj Hospital, Mahidol University
Keywords: Medicine
Issue Date: 22-Mar-2018
Citation: Respiratory Research. Vol.19, No.1 (2018)
Abstract: © 2018 The Author(s). Background: Genome-wide association studies have identified several genetic risk loci for severe chronic obstructive pulmonary disease (COPD) and emphysema. However, these studies do not fully explain disease heritability and in most cases, fail to implicate specific genes. Integrative methods that combine gene expression data with GWAS can provide more power in discovering disease-associated genes and give mechanistic insight into regulated genes. Methods: We applied a recently described method that imputes gene expression using reference transcriptome data to genome-wide association studies for two phenotypes (severe COPD and quantitative emphysema) and blood and lung tissue gene expression datasets. We further tested the potential causality of individual genes using multi-variant colocalization. Results: We identified seven genes significantly associated with severe COPD, and five genes significantly associated with quantitative emphysema in whole blood or lung. We validated results in independent transcriptome databases and confirmed colocalization signals for PSMA4, EGLN2, WNT3, DCBLD1, and LILRA3. Three of these genes were not located within previously reported GWAS loci for either phenotype. We also identified genetically driven pathways, including those related to immune regulation. Conclusions: An integrative analysis of GWAS and gene expression identified novel associations with severe COPD and quantitative emphysema, and also suggested disease-associated genes in known COPD susceptibility loci.
ISSN: 1465993X
Appears in Collections:Scopus 2018

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