Journal article
Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
Nature genetics, Vol.51(3), pp.494-505
03/2019
DOI: 10.1038/s41588-018-0342-2
PMCID: PMC6546635
PMID: 30804561
Abstract
Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 × 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
Details
- Title: Subtitle
- Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- Creators
- Phuwanat SakornsakolpatDmitry ProkopenkoMaxime LamontagneNicola F Reeve - University of LeicesterAnna L Guyatt - University of LeicesterVictoria E JacksonNick ShrineDandi Qiao - Brigham and Women's HospitalTraci M BartzDeog Kyeom Kim - Seoul National UniversityMi Kyeong LeeJeanne C LatourelleXingnan Li - University of ArizonaJarrett D Morrow - Brigham and Women's HospitalMa'en Obeidat - University of British ColumbiaAnnah B Wyss - National Institutes of HealthPer BakkeR Graham Barr - Columbia University Irving Medical CenterTerri H Beaty - Johns Hopkins UniversitySteven A BelinskyGuy G BrusselleJames D Crapo - National Jewish HealthKim de JongDawn L DeMeo - Brigham and Women's HospitalTasha E Fingerlin - National Jewish HealthSina A Gharib - University of WashingtonAmund GulsvikIan P HallJohn E Hokanson - Colorado School of Public HealthWoo Jin KimDavid A LomasStephanie J London - National Institutes of HealthDeborah A Meyers - Wake Forest UniversityGeorge T O'Connor - Boston UniversityStephen I Rennard - University of MichiganDavid A Schwartz - University of Colorado DenverPawel SliwinskiDavid SparrowDavid P StrachanRuth Tal-Singer - University Hospitals Birmingham NHS Foundation TrustYohannes TesfaigziJørgen VestboJudith M VonkJae-Joon YimXiaobo ZhouYohan BosséAni Manichaikul - University of VirginiaLies LahousseEdwin K Silverman - Brigham and Women's HospitalH Marike Boezen - University Medical Center GroningenSpiroMeta ConsortiumInternational COPD Genetics Consortium
- Contributors
- Eric Hoffman (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.51(3), pp.494-505
- DOI
- 10.1038/s41588-018-0342-2
- PMID
- 30804561
- PMCID
- PMC6546635
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984318802802771
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