Nature genetics · 2017

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

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Hobbs Brian D, de Jong Kim, Lamontagne Maxime, Bossé Yohan, Shrine Nick, Artigas María Soler, Wain Louise V, Hall Ian P, Jackson Victoria E, Wyss Annah B, London Stephanie J, North Kari E, Franceschini Nora, Strachan David P, Beaty Terri H, Hokanson John E, Crapo James D, Castaldi Peter J, Chase Robert P, Bartz Traci M, Heckbert Susan R, Psaty Bruce M, Gharib Sina A, Zanen Pieter, Lammers Jan W, Oudkerk Matthijs, Groen H J, Locantore Nicholas, Tal-Singer Ruth, Rennard Stephen I, Vestbo Jørgen, Timens Wim, Paré Peter D, Latourelle Jeanne C, Dupuis Josée, O'Connor George T, Wilk Jemma B, Kim Woo Jin, Lee Mi Kyeong, Oh Yeon-Mok, Vonk Judith M, de Koning Harry J, Leng Shuguang, Belinsky Steven A, Tesfaigzi Yohannes, Manichaikul Ani, Wang Xin-Qun, Rich Stephen S, Barr R Graham, Sparrow David, Litonjua Augusto A, Bakke Per, Gulsvik Amund, Lahousse Lies, Brusselle Guy G, Stricker Bruno H, Uitterlinden André G, Ampleford Elizabeth J, Bleecker Eugene R, Woodruff Prescott G, Meyers Deborah A, Qiao Dandi, Lomas David A, Yim Jae-Joon, Kim Deog Kyeom, Hawrylkiewicz Iwona, Sliwinski Pawel, Hardin Megan, Fingerlin Tasha E, Schwartz David A, Postma Dirkje S, MacNee William, Tobin Martin D, Silverman Edwin K, Boezen H Marike, Cho Michael H, COPDGene Investigators, ECLIPSE Investigators, LifeLines Investigators, SPIROMICS Research Group, International COPD Genetics Network Investigators, UK BiLEVE Investigators, International COPD Genetics Consortium

Аннотация

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

Предметные рубрики MeSH

Adult Aged Aged, 80 and over Alleles Asthma Female Genetic Loci Genetic Predisposition to Disease Genome-Wide Association Study Humans Lung Male Middle Aged Phenotype Polymorphism, Single Nucleotide Pulmonary Disease, Chronic Obstructive Pulmonary Fibrosis Risk Factors Smoking

Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.

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Аннотация

Предметные рубрики MeSH