Advanced search
1 file | 492.55 KB Add to list

Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts

(2020) LANCET RESPIRATORY MEDICINE. 8(7). p.696-708
Author
Organization
Abstract
Background 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. Methods We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/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 FEV1/FVC <0.7 and FEV1 <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. Findings 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. Interpretation 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.
Keywords
GENOME-WIDE ASSOCIATION, AMERICAN THORACIC SOCIETY, LUNG-FUNCTION, GENETIC EPIDEMIOLOGY, FAMILIAL AGGREGATION, SMOKING-BEHAVIOR, COPD, EMPHYSEMA, LOCI, HERITABILITY

Downloads

  • 8673080.pdf
    • full text (Published version)
    • |
    • open access
    • |
    • PDF
    • |
    • 492.55 KB

Citation

Please use this url to cite or link to this publication:

MLA
Moll, Matthew, et al. “Chronic Obstructive Pulmonary Disease and Related Phenotypes: Polygenic Risk Scores in Population-Based and Case-Control Cohorts.” LANCET RESPIRATORY MEDICINE, vol. 8, no. 7, Elsevier Sci Ltd, 2020, pp. 696–708.
APA
Moll, M., Sakornsakolpat, P., Shrine, N., Hobbs, B. D., DeMeo, D. L., John, C., … Cho, M. H. (2020). Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts. LANCET RESPIRATORY MEDICINE, 8(7), 696–708.
Chicago author-date
Moll, Matthew, Phuwanat Sakornsakolpat, Nick Shrine, Brian D. Hobbs, Dawn L. DeMeo, Catherine John, Anna L. Guyatt, et al. 2020. “Chronic Obstructive Pulmonary Disease and Related Phenotypes: Polygenic Risk Scores in Population-Based and Case-Control Cohorts.” LANCET RESPIRATORY MEDICINE 8 (7): 696–708.
Chicago author-date (all authors)
Moll, Matthew, Phuwanat Sakornsakolpat, Nick Shrine, Brian D. Hobbs, Dawn L. DeMeo, Catherine John, Anna L. Guyatt, Michael J. McGeachie, Sina A. Gharib, Ma’en Obeidat, Lies Lahousse, Sara Wijnant, Guy Brusselle, Deborah A. Meyers, Eugene R. Bleecker, Xingnan Li, Ruth Tal-Singer, Ani Manichaikul, Stephen S. Rich, Sungho Won, Woo Jin Kim, Ah Ra Do, George R. Washko, R. Graham Barr, Bruce M. Psaty, Traci M. Bartz, Nadia N. Hansel, Kathleen Barnes, John E. Hokanson, James D. Crapo, David Lynch, Per Bakke, Amund Gulsvik, Ian P. Hall, Louise Wain, Scott T. Weiss, Edwin K. Silverman, Frank Dudbridge, Martin D. Tobin, and Michael H. Cho. 2020. “Chronic Obstructive Pulmonary Disease and Related Phenotypes: Polygenic Risk Scores in Population-Based and Case-Control Cohorts.” LANCET RESPIRATORY MEDICINE 8 (7): 696–708.
Vancouver
1.
Moll M, Sakornsakolpat P, Shrine N, Hobbs BD, DeMeo DL, John C, et al. Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts. LANCET RESPIRATORY MEDICINE. 2020;8(7):696–708.
IEEE
[1]
M. Moll et al., “Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts,” LANCET RESPIRATORY MEDICINE, vol. 8, no. 7, pp. 696–708, 2020.
@article{8675489,
  abstract     = {Background 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. Methods We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/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 FEV1/FVC <0.7 and FEV1 <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. Findings 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. Interpretation 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.},
  author       = {Moll, Matthew and Sakornsakolpat, Phuwanat and Shrine, Nick and Hobbs, Brian D. and DeMeo, Dawn L. and John, Catherine and Guyatt, Anna L. and McGeachie, Michael J. and Gharib, Sina A. and Obeidat, Ma'en and Lahousse, Lies and Wijnant, Sara and Brusselle, Guy and Meyers, Deborah A. and Bleecker, Eugene R. and Li, Xingnan and Tal-Singer, Ruth and Manichaikul, Ani and Rich, Stephen S. and Won, Sungho and Kim, Woo Jin and Do, Ah Ra and Washko, George R. and Barr, R. Graham and Psaty, Bruce M. and Bartz, Traci M. and Hansel, Nadia N. and Barnes, Kathleen and Hokanson, John E. and Crapo, James D. and Lynch, David and Bakke, Per and Gulsvik, Amund and Hall, Ian P. and Wain, Louise and Weiss, Scott T. and Silverman, Edwin K. and Dudbridge, Frank and Tobin, Martin D. and Cho, Michael H.},
  issn         = {2213-2600},
  journal      = {LANCET RESPIRATORY MEDICINE},
  keywords     = {GENOME-WIDE ASSOCIATION,AMERICAN THORACIC SOCIETY,LUNG-FUNCTION,GENETIC EPIDEMIOLOGY,FAMILIAL AGGREGATION,SMOKING-BEHAVIOR,COPD,EMPHYSEMA,LOCI,HERITABILITY},
  language     = {eng},
  number       = {7},
  pages        = {696--708},
  publisher    = {Elsevier Sci Ltd},
  title        = {Chronic obstructive pulmonary disease and related phenotypes: polygenic risk scores in population-based and case-control cohorts},
  volume       = {8},
  year         = {2020},
}

Web of Science
Times cited: