Associations of genetic risk and smoking with incident COPD

作者：Zhang, Pei-Dong; Zhang, Xi-Ru; Zhang, Ao; Li, Zhi-Hao; Liu, Dan; Zhang, Yu-Jie; Mao, Chen^*

来源：European Respiratory Journal, 2022, 59(2): 2101320.

DOI：10.1183/13993003.01320-2021

• OBSTRUCTIVE PULMONARY-DISEASE
• GENOME-WIDE ASSOCIATION
• LUNG-FUNCTION
• VARIANTS
• SCORES
• METAANALYSIS
• IMPUTATION
• REGRESSION
• BEHAVIOR
• SOCIETY

Background Genetic factors and smoking contribute to chronic obstructive pulmonary disease (COPD), but whether a combined polygenic risk score (PRS) is associated with incident COPD and whether it has a synergistic effect on smoking remains unclear. We aimed to investigate the association of the PRS with COPD and explore whether smoking behaviours could modify such association. @@@ Methods Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals for the association of the PRS and smoking with COPD. @@@ Results The study included 439255 participants (mean age 56.5 years; 53.9% female), with a median follow-up of 9.0 years. PRSlasso containing 2.5 million variants showed better discrimination and a stronger association for incident COPD than PRS279 containing 279 genome-wide significance variants. Compared with low genetic risk, the HRs of medium and high genetic risk were 1.39 (95% CI 1.31-1.48) and 2.40 (95% CI 2.24-2.56), respectively. The HR of high genetic risk and current smoking was 11.62 (95% CI 10.31-13.10) times that of low genetic risk and never smoking. There were significant interactions between PRSlasso and smoking status for incident COPD (pinteraction<0.001). From low genetic risk to high genetic risk, the HRs of current smoking increased from 4.32 (95% CI 3.69-5.06) to 6.89 (95% CI 6.21-7.64) and the population-attributable risks of smoking increased from 42.7% to 61.1%. @@@ Conclusions The PRS constructed from millions of variants below genome-wide significance showed significant associations with incident COPD. Participants with a high genetic risk may be more susceptible to developing COPD when exposed to smoking.

• 单位
  南方医科大学