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A polygenic risk score for asthma in a large racially diverse population
Author(s) -
Sordillo Joanne E.,
Lutz Sharon M.,
Jorgenson Eric,
Iribarren Carlos,
McGeachie Michael,
Dahlin Amber,
Tantisira Kelan,
Kelly Rachel,
LaskySu Jessica,
Sakornsakolpat Phuwanat,
Moll Matthew,
Cho Michael H.,
Wu Ann Chen
Publication year - 2021
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.14007
Subject(s) - polygenic risk score , asthma , medicine , population , demography , biology , environmental health , genetics , genotype , single nucleotide polymorphism , gene , sociology
Background Polygenic risk scores (PRSs) will have important utility for asthma and other chronic diseases as a tool for predicting disease incidence and subphenotypes. Objective We utilized findings from a large multiancestry GWAS of asthma to compute a PRS for asthma with relevance for racially diverse populations. Methods 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 (68 638 non‐Hispanic Whites, 5874 Hispanics, 6870 Asians and 2760 Blacks). Race was self‐reported by questionnaire. Results 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)). Conclusion 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.