Genetic loci associated with chronic obstructive pulmonary disease overlap with loci for lung function and pulmonary fibrosis.
Brian D HobbsKim de JongMaxime LamontagneYohan BosseNick ShrineMaría Soler ArtigasLouise V WainIan P HallVictoria E JacksonAnnah B WyssStephanie J LondonKari E NorthNora FranceschiniDavid P StrachanTerri H BeatyJohn E HokansonJames D CrapoPeter J CastaldiRobert P ChaseTraci M BartzSusan R HeckbertBruce M PsatySina A GharibPieter ZanenJan W LammersMatthijs OudkerkH J GroenNicholas LocantoreRuth Tal-SingerStephen I RennardJørgen VestboHidde J HaismaPeter D ParéJeanne C LatourelleJosée DupuisGeorge T O'ConnorJemma B WilkWoo Jin KimMi Kyeong LeeYeon-Mok OhJudith M VonkHarry J de KoningShuguang LengSteven A BelinskyYohannes TesfaigziAni ManichaikulXin-Qun WangStephen S RichR Graham BarrDavid SparrowAugusto A LitonjuaPer BakkeAmund GulsvikLies LahousseGuy G BrusselleBruno H StrickerAndré G UitterlindenElizabeth J AmplefordEugene R BleeckerPrescott G WoodruffDeborah A MeyersDandi QiaoDavid A LomasJae-Joon YimDeog Kyeom KimIwona HawrylkiewiczPawel SliwinskiMegan HardinTasha E FingerlinDavid A SchwartzDirkje S PostmaWilliam MacNeeMartin D TobinEdwin K SilvermanH Marike BoezenMichael H Chonull nullnull nullnull nullnull nullnull nullnull nullnull nullPublished in: Nature genetics (2017)
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.
Keyphrases
- lung function
- genome wide
- chronic obstructive pulmonary disease
- dna methylation
- cystic fibrosis
- air pollution
- copy number
- pulmonary fibrosis
- genome wide association study
- systematic review
- genome wide association
- metabolic syndrome
- type diabetes
- gene expression
- coronary artery disease
- body mass index
- climate change
- skeletal muscle