A Genetic Risk Score Associated with Chronic Obstructive Pulmonary Disease Susceptibility and Lung Structure on Computed Tomography

Oelsner, Elizabeth C.; Ortega, Victor E.; Smith, Benjamin M.; Nguyen, Jennifer; Manichaikul, Ani; Hoffman, Eric A.; Guo, Xiuqing; Taylor, Kent D.; Woodruff, Prescott G.; Couper, David J.; Hansel, Nadia N.; Martínez, Fernando J.; Paine, Robert; Han, MeiLan K.; Cooper, Christopher B.; Dransfield, Mark T.; Criner, Gerard J.; Krishnan, Jerry A.; Bowler, Russell P.; Bleecker, Eugene R.; Peters, Stephen P.; Rich, Stephen S.; Meyers, Deborah A.; Rotter, Jerome I.; Barr, R. Graham

doi:10.1164/rccm.201812-2355oc

Cited by 41 publications

(27 citation statements)

References 63 publications

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“…This score used more variants and larger sample sizes than previous studies, and was tested in a greater number of validation cohorts. 7 , 11 , 14 , 16 The score was also associated with CT imaging phenotypes and patterns of reduced lung growth that could predispose individuals to COPD.…”

Section: Discussionmentioning

confidence: 98%

“…Individuals with COPD can have widely varying airway and lung parenchymal involvement, and individual COPD GWAS variants are associated with quantitative imaging features, such as airway wall thickness and emphysema. 8 , 9 , 10 Oelsner and colleagues 16 derived a 79-variant genetic risk score from a previous GWAS for lung function 11 and identified an association with quantitative imaging features on chest CT. However, whether a genetic risk score comprised of a larger number of lung function variants would result in stronger associations with a wider range of quantitative and qualitative CT imaging features is not known.…”

Section: Introductionmentioning

confidence: 99%

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

Moll

Sakornsakolpat

Shrine

et al. 2020

The Lancet Respiratory Medicine

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Summary 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 (FEV 1 and FEV 1 /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 1 /FVC <0·7 and FEV 1 <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. Funding US National Institutes of Health, Wellcome Trust.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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

Moll

Sakornsakolpat

Shrine

et al. 2020

The Lancet Respiratory Medicine

View full text Add to dashboard Cite

show abstract

“…Severe COPD exacerbations are associated with accelerated decline in lung function especially among those with less severe airflow obstruction . There is increasing interest in using clinical traits, phenotypic information and genetics to identify COPD patients and most importantly predict their outcomes …”

Section: Disclosure Statementmentioning

confidence: 99%

“…5 There is increasing interest in using clinical traits, phenotypic information and genetics to identify COPD patients and most importantly predict their outcomes. 6 There has also been rapid advancement in thoracic imaging especially in the use of chest CT to phenotype COPD patients. CT are now routinely used to quantify the burden of emphysema (using both lung densitometry for quantitative analysis and qualitative reading by trained radiologists) and small airway disease (by counting airways and functional small airway imaging) in COPD patients.…”

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confidence: 99%

Twenty‐five years of Respirology: Advances in COPD

Sin

2019

Respirology

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“…In this issue of the Journal , Oelsner and colleagues (pp. 721–731) provide us with new information that addresses this problem (7). They used a weighted genetic risk score (GRS) for impaired lung function based on 95 SNPs, including those already identified in multiple data sets as relating to lung function and the new candidates from the UK study (6).…”

mentioning

confidence: 99%