A polygenic risk score for asthma in a large racially diverse population.

Abstract

Polygenic risk scores (PRSs) will have important utility for asthma and other chronic diseases as a tool for predicting disease incidence and subphenotypes. We utilized findings from a large multiancestry GWAS of asthma to compute a PRS for asthma with relevance for racially diverse populations. We derived two PRSs for asthma using a standard approach (based on genome-wide significant variants) and a lasso sum regression approach (allowing all genetic variants to potentially contribute). We used data from the racially diverse Kaiser Permanente GERA cohort (68638non-Hispanic Whites, 5874 Hispanics, 6870 Asians and 2760 Blacks). Race was self-reported by questionnaire. For the standard PRS, non-Hispanic Whites showed the highest odds ratio for a standard deviation increase in PRS for asthma (OR=1.16 (95% CI 1.14-1.18)). The standard PRS was also associated with asthma in Hispanic (OR=1.12 (95% CI 1.05-1.19)) and Asian (OR=1.10 (95% CI 1.04-1.17)) subjects, with a trend towards increased risk in Blacks (OR=1.05 (95% CI 0.97-1.15)). We detected an interaction by sex, with men showing a higher risk of asthma with an increase in PRS as compared to women. The lasso sum regression-derived PRS showed stronger associations with asthma in non-Hispanic White subjects (OR=1.20 (95% CI 1.18-1.23)), Hispanics (OR=1.17 (95% 1.10-1.26)), Asians (OR=1.18 (95% CI 1.10-1.27)) and Blacks (OR=1.10 (95% CI 0.99-1.22)). Polygenic risk scores across multiple racial/ethnic groups were associated with increased asthma risk, suggesting that PRSs have potential as a tool for predicting disease development.