A Between Ethnicities Comparison of Chronic Obstructive Pulmonary Disease Genetic Risk

Abstract

Heterogeneity of lung function levels and risk for developing chronic obstructive pulmonary disease (COPD) among people exposed to the same environmental risk factors, such as cigarette smoking, suggest an important role of genetic factors in COPD susceptibility. To investigate the possible role of different genetic factors in COPD susceptibility across ethnicities. We used a population-stratified analysis for: (i) identifying ethnic-specific genetic susceptibility loci, (ii) developing ethnic-specific polygenic risk prediction models using those SNPs, and (iii) validating the models with an independent dataset. We elucidated substantial differences in SNP heritability and susceptibility loci for the disease across ethnicities. Furthermore, the application of three ethnic-specific prediction models to an independent dataset showed that the best performance is achieved when the prediction model is applied to a dataset with the matched ethnic sample. Our study validates the necessity of considering ethnic differences in COPD risk; understanding these differences might help in preventing COPD and developing therapeutic strategies.

Keywords: BLUP-filtered SNP; COPD; SNP heritability; ethnicity difference; ethnicity-specific; genetic prediction; susceptible loci.