Title | Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis. |
Publication Type | Publication |
Year | 2017 |
Authors | Hobbs 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 Authors | COPDGene Investigators, ECLIPSE Investigators, LifeLines Investigators, SPIROMICS Research Group, International COPD Genetics Network Investigators, UK BiLEVE Investigators, International COPD Genetics Consortium |
Journal | Nat Genet |
Volume | 49 |
Issue | 3 |
Pagination | 426-432 |
Date Published | 2017 Mar |
ISSN | 1546-1718 |
Keywords | 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 |
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. |
DOI | 10.1038/ng.3752 |
Alternate Journal | Nat Genet |
PubMed ID | 28166215 |
PubMed Central ID | PMC5381275 |
Grant List | R01 HL113264 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States K08 HL097029 / HL / NHLBI NIH HHS / United States R01 HL075478 / HL / NHLBI NIH HHS / United States MC_PC_12010 / MRC_ / Medical Research Council / United Kingdom P01 HL105339 / HL / NHLBI NIH HHS / United States U01 HL137880 / HL / NHLBI NIH HHS / United States K01 HL129039 / HL / NHLBI NIH HHS / United States R01 HL124233 / HL / NHLBI NIH HHS / United States R33 HL120770 / HL / NHLBI NIH HHS / United States 202849/Z/16/Z / WT_ / Wellcome Trust / United Kingdom T32 HL007427 / 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 R01 HL120393 / HL / NHLBI NIH HHS / United States S10 OD018526 / OD / NIH HHS / United States U01 HL120393 / HL / NHLBI NIH HHS / United States U01 HL089897 / HL / NHLBI NIH HHS / United States MR/N024842/1 / MRC_ / Medical Research Council / United Kingdom R01 HL077612 / HL / NHLBI NIH HHS / United States R01 HL089856 / HL / NHLBI NIH HHS / United States G0902313 / MRC_ / Medical Research Council / United Kingdom R01 HL093081 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01 HL089856 / HL / NHLBI NIH HHS / United States G1000861 / MRC_ / Medical Research Council / United Kingdom R01 HL126596 / HL / NHLBI NIH HHS / United States R01 HL097163 / HL / NHLBI NIH HHS / United States MR/N011317/1 / MRC_ / Medical Research Council / United Kingdom R01 HL084323 / HL / NHLBI NIH HHS / United States P01 HL114501 / HL / NHLBI NIH HHS / United States |
Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.
MS#:
MS072
Manuscript Full Title:
Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.
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