Genome-Wide Association Analysis of Single-Breath D l CO
Year: 2019
Type: article
Study design: Observational Study
Abstract: Dl CO is a widely used pulmonary function test in clinical practice and a particularly useful measure for assessing patients with chronic obstructive pulmonary disease (COPD). We hypothesized that elucidating genetic determinants of Dl CO could lead to better understanding of the genetic architecture of COPD. We estimated the heritability of Dl CO using common genetic variants and performed genome-wide association analyses in four cohorts enriched for subjects with COPD (COPDGene [Genetic Epidemiology of COPD], NETT [National Emphysema Treatment Trial], GenKOLS [Genetics of Chronic Obstructive Lung Disease study], and TESRA [Treatment of Emphysema With a Gamma-Selective Retinoid Agonist study]) using a combined European ancestry white dataset and a COPDGene African American dataset. We assessed our genome-wide significant and suggestive associations for Dl CO in previously reported genome-wide association studies of COPD and related traits. We also characterized associations of known COPD-associated variants and Dl CO. We estimated the SNP-based heritability of Dl CO in the European ancestry white population to be 22% (P = 0.0004). We identified three genome-wide significant associations with Dl CO: variants near TGFB2, CHRNA3, and PDE11A loci (P < 5 × 10−8). In addition, 12 loci were suggestively associated with Dl CO in European ancestry white (P < 1 × 10−5 in the combined analysis and P < 0.05 in both COPDGene and GenKOLS), including variants near NEGR1, CADM2, PCDH7, RETREG1, DACT2, NRG1, ANKRD18A, KRT86, NTN4, ARHGAP28, INSR, and PCBP3. Some Dl CO-associated variants were also associated with COPD, emphysema, and/or spirometric values. Among 25 previously reported COPD loci, TGFB2, CHRNA3/CHRNA5, FAM13A, DSP, and CYP2A6 were associated with Dl CO (P < 0.001). We identified several genetic loci that were significantly associated with Dl CO and characterized effects of known COPD-associated loci on Dl CO. These results could lead to better understanding of the heterogeneous nature of COPD.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G1207659464, G1220799682, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, G1439225947, G1576662596, G1605453878, G1615620936, G1617588125, CLINICAL CENTER FOR LVRS, G1735610881, CLNICAL CENTER FOR LVRS, CLNICAL CENTER FOR LVRS, G182694510, LUNG VOLUME REDUCTION STUDY--CLINICAL CENTER, Identifying Genetic Determinants of Severe, Early-Onset COPD, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G226397431, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2412257637, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, G2599011918, G278468722, G3110798224, Identifying functional variants in COPD GWAS loci, G3146753889, CLINICAL COORDINATING CENTER FOR LVRS, Systems Biology of Airway Disease, G3715945925, G3805264881, G3874500373, G4153249725, Genetic Determinants of COPD in Diverse Ethnic Groups, (2 of 2) Genetic Epidemiology of COPD, G4255341634, G468516202, G48533833, G5181772611, G520825964, G5258357286, G5484345081, G556935766, Functional Genetics of COPD, (1 of 2) Genetic Epidemiology of COPD, (2 of 2) Genetic Epidemiology of COPD, G5791858519, G6315211796, CLNICAL CENTER FOR THE LVRS, Community Assist of Southern Arizona, G6570314638, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, CLINICAL CENTER FOR LVRS, (1 of 2) Genetic Epidemiology of COPD, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G6996658085, G7092741763, G7218825848, G7541302268, G754838926, G778147052, G7949433598, G8081622010, G820522361, G8354759825, G8643874822, G8819318481, G8938195782, LUNG VOLUME REDUCTION SURGERY--CLINICAL CENTER, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, CLINICAL CENTER FOR THE LUNG VOLUME REDUCTION SURGERY, G943488547
OpenAlex ID: W2913742731