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Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts.
Monday,2020-08-24 18:40 America/Los_Angeles — ecterry
| Title | Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts. |
| Publication Type | Journal Article |
| Year of Publication | 2020 |
| Authors | Moll, M, Sakornsakolpat, P, Shrine, N, Hobbs, BD, DeMeo, DL, John, C, Guyatt, AL, McGeachie, MJ, Gharib, SA, Obeidat, M'en, Lahousse, L, Wijnant, SRA, Brusselle, G, Meyers, DA, Bleecker, ER, Li, X, Tal-Singer, R, Manichaikul, A, Rich, SS, Won, S, Kim, WJin, Do, ARa, Washko, GR, R Barr, G, Psaty, BM, Bartz, TM, Hansel, NN, Barnes, K, Hokanson, JE, Crapo, JD, Lynch, D, Bakke, P, Gulsvik, A, Hall, IP, Wain, L, Weiss, ST, Silverman, EK, Dudbridge, F, Tobin, MD, Cho, MH |
| Corporate/Institutional Authors | International COPD Genetics Consortium, SpiroMeta Consortium |
| Journal | Lancet Respir Med |
| Volume | 8 |
| Issue | 7 |
| Pagination | 696-708 |
| Date Published | 2020 07 |
| ISSN | 2213-2619 |
| Keywords | Adult, Case-Control Studies, Cohort Studies, Female, Forced Expiratory Volume, Genome-Wide Association Study, Humans, Male, Middle Aged, Phenotype, Pulmonary Disease, Chronic Obstructive, Risk Factors, Vital Capacity |
| Abstract | <p><b>BACKGROUND: </b>Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes.</p><p><b>METHODS: </b>We constructed a polygenic risk score using a genome-wide association study of lung function (FEV and FEV/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV/FVC <0·7 and FEV <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth.</p><p><b>FINDINGS: </b>The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74-1·88] and non-European (1·42 [1·34-1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56-9·72) in European ancestry and 4·83 (3·45-6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79-0·81] vs 0·76 [0·75-0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern.</p><p><b>INTERPRETATION: </b>A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth.</p><p><b>FUNDING: </b>US National Institutes of Health, Wellcome Trust.</p> |
| DOI | 10.1016/S2213-2600(20)30101-6 |
| Alternate Journal | Lancet Respir Med |
| PubMed ID | 32649918 |
| PubMed Central ID | PMC7429152 |
| Grant List | R01 HL113264 / HL / NHLBI NIH HHS / United States R01 HL147148 / HL / NHLBI NIH HHS / United States R01 HL135142 / HL / NHLBI NIH HHS / United States R01 HL137927 / HL / NHLBI NIH HHS / United States K08 HL136928 / HL / NHLBI NIH HHS / United States R01 HL131565 / HL / NHLBI NIH HHS / United States P01 HL132825 / HL / NHLBI NIH HHS / United States T32 HL007427 / HL / NHLBI NIH HHS / United States R01 HL133135 / HL / NHLBI NIH HHS / United States R01 HL139634 / HL / NHLBI NIH HHS / United States |
ePub date:
20/07