Dataset Information

Genetic Risk and Chronic Obstructive Pulmonary Disease Independently Predict the Risk of Incident Severe COVID-19.

ABSTRACT: Rationale: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods: We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results: Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P < 0.001) than those at low genetic risk and without COPD. Conclusions: The polygenic risk score, which combines multiple risk alleles, can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of preexisting COPD.

SUBMITTER: Huang QM

PROVIDER: S-EPMC8787794 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Genetic Risk and Chronic Obstructive Pulmonary Disease Independently Predict the Risk of Incident Severe COVID-19.

Huang Qing-Mei QM Zhang Pei-Dong PD Li Zhi-Hao ZH Zhou Jian-Meng JM Liu Dan D Zhang Xi-Ru XR Zhong Wen-Fang WF Zhang Yu-Jie YJ Shen Dong D Liang Fen F Song Wei-Qi WQ Yang Shi-Gui SG Guan Wei-Jie WJ Mao Chen C

Annals of the American Thoracic Society 20220101 1

Rationale: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods: We constructed a polygenic risk score for severe COVID-19 by using 112 ...[more]

PMID: 34242153

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Project description:RationaleChronic lower respiratory diseases (CLRDs), including chronic obstructive pulmonary disease (COPD) and asthma, are the fourth leading cause of death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in patients with COPD.ObjectivesTo test whether albuminuria was associated with lung function decline and incident CLRDs.MethodsSix U.S. population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth year, cohort, smoking status, pack-years of smoking, renal function, hypertension, diabetes, and medications.Measurements and main resultsAmong 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6 mg/g, and mean FEV1 decline was 31.5 ml/yr. For each SD increase in log-transformed albuminuria, there was 2.81% greater FEV1 decline (95% confidence interval [CI], 0.86-4.76%; P = 0.0047), 11.02% greater FEV1/FVC decline (95% CI, 4.43-17.62%; P = 0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P = 0.0021). Each SD log-transformed albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P < 0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease.ConclusionsAlbuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a U.S. population-based sample.

Project description:BackgroundChronic obstructive pulmonary disease (COPD) is closely linked to lung cancer (LC) development. The aim of this study is to identify the genetic and clinical risk factors for LC risk in COPD, according to which the prediction model for LC in COPD was constructed.MethodsThis is a case-control study in which patientis with COPD + LC as the case group, patientis with only COPD as the control group, and patientis with only LC as the second control group. A panel of clinical variables including demographic, environmental and lifestyle factors were collected. A total of 20 single nucleotide polymorphisms (SNPs) were genotyped. The univariate analysis, candidate gene study and multivariate analysis were applied to identify the independent risk factors, as well as the prediction model was constructed. The ROC analysis was used to evaluate the predictive ability of the model.ResultsA total of 503 patients were finally enrolled in this study, with 188 patients for COPD + LC group, 162 patients for COPD group and 153 patients for LC group. The univariate analysis of clincial data showed compared with the patients with COPD, the patients with COPD + LC tended to have significantly lower BMI, higher smoking pack-years, and higher prevalence of emphysema. The results of the candidate gene study showed the rs1489759 in HHIP and rs56113850 in CYP2A6 demonstrated significant differences between COPD and COPD + LC groups. By using multivariate logistic regression analysis, four variables including BMI, pack-years, emphysema and rs56113850 were identified as independent risk factors for LC in COPD and the prediction model integrating genetic and clinical data was constructed. The AUC of the prediction model for LC in COPD reached 0.712, and the AUC of the model for predicting LC in serious COPD reached up to 0.836.ConclusionThe rs56113850 (risk allele C) in CYP2A6, decrease in BMI, increase in pack-years and emphysema presence were independent risk factors for LC in COPD. Integrating genetic and clinical data for predicting LC in COPD demonstrated favorable predictive performance.

Dataset Information

Genetic Risk and Chronic Obstructive Pulmonary Disease Independently Predict the Risk of Incident Severe COVID-19.

Publications

Genetic Risk and Chronic Obstructive Pulmonary Disease Independently Predict the Risk of Incident Severe COVID-19.

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