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

TitleGenetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.
Publication TypePublication
Year2017
AuthorsHobbs BD, de Jong K, Lamontagne M, Bossé Y, Shrine N, Artigas MSoler, Wain LV, Hall IP, Jackson VE, Wyss AB, London SJ, North KE, Franceschini N, Strachan DP, Beaty TH, Hokanson JE, Crapo JD, Castaldi PJ, Chase RP, Bartz TM, Heckbert SR, Psaty BM, Gharib SA, Zanen P, Lammers JW, Oudkerk M, Groen HJ, Locantore N, Tal-Singer R, Rennard SI, Vestbo J, Timens W, Paré PD, Latourelle JC, Dupuis J, O'Connor GT, Wilk JB, Kim WJin, Lee MKyeong, Oh Y-M, Vonk JM, de Koning HJ, Leng S, Belinsky SA, Tesfaigzi Y, Manichaikul A, Wang X-Q, Rich SS, R Barr G, Sparrow D, Litonjua AA, Bakke P, Gulsvik A, Lahousse L, Brusselle GG, Stricker BH, Uitterlinden AG, Ampleford EJ, Bleecker ER, Woodruff PG, Meyers DA, Qiao D, Lomas DA, Yim J-J, Kim DKyeom, Hawrylkiewicz I, Sliwinski P, Hardin M, Fingerlin TE, Schwartz DA, Postma DS, MacNee W, Tobin MD, Silverman EK, H Boezen M, Cho MH
Corporate AuthorsCOPDGene Investigators, ECLIPSE Investigators, LifeLines Investigators, SPIROMICS Research Group, International COPD Genetics Network Investigators, UK BiLEVE Investigators, International COPD Genetics Consortium
JournalNat Genet
Volume49
Issue3
Pagination426-432
Date Published2017 Mar
ISSN1546-1718
KeywordsAdult, 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
Abstract

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) 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.

DOI10.1038/ng.3752
Alternate JournalNat. Genet.
PubMed ID28166215
PubMed Central IDPMC5381275
Grant ListR01 HL113264 / HL / NHLBI NIH HHS / United States
R01 HL089897 / HL / NHLBI NIH HHS / United States
P01 HL092870 / HL / NHLBI NIH HHS / United States
P30 CA118100 / CA / NCI NIH HHS / United States
S10 OD018526 / OD / NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
K08 HL097029 / HL / NHLBI NIH HHS / United States
U01 HL089897 / HL / NHLBI NIH HHS / United States
R01 HL077612 / HL / NHLBI NIH HHS / United States
G1000861 / / Medical Research Council / United Kingdom
R01 HL075478 / HL / NHLBI NIH HHS / United States
MC_PC_12010 / / Medical Research Council / United Kingdom
R01 HL089856 / HL / NHLBI NIH HHS / United States
R01 HL093081 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01 HL089856 / HL / NHLBI NIH HHS / United States
P01 HL105339 / HL / NHLBI NIH HHS / United States
R01 HL126596 / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
K01 HL129039 / HL / NHLBI NIH HHS / United States
G0902313 / / Medical Research Council / United Kingdom
R01 HL124233 / HL / NHLBI NIH HHS / United States
R01 HL084323 / HL / NHLBI NIH HHS / United States
P01 HL114501 / HL / NHLBI NIH HHS / United States
T32 HL007427 / HL / NHLBI NIH HHS / United States
MS#: 
MS072
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Winston-Salem (Wake Forest University Health Sciences)
ECI: 
Manuscript Status: 
Published