Lehto K, Pedersen NL, Almqvist C, Lu Y, Brew BK
Eur. Respir. J. 53 (5) 1802142 [2019-05-00; online 2019-05-30]
Depression, anxiety and high neuroticism (affective traits) are often comorbid with asthma. A causal direction between the affective traits and asthma is difficult to determine; however, there may be a common underlying pathway attributable to shared genetic factors. Our aim was to determine whether a common genetic susceptibility exists for asthma and each of the affective traits.An adult cohort from the Swedish Twin Registry underwent questionnaire-based health assessments (n=23 693) and genotyping (n=15 908). Firstly, questionnaire-based associations between asthma and affective traits were explored. This was followed by genetic analyses: 1) polygenic risk scores (PRS) for affective traits were used as predictors of asthma in the cohort, and 2) genome-wide association results from UK Biobank were used in linkage-disequilibrium score regression (LDSC) to quantify genetic correlations between asthma and affective traits. Analyses found associations between questionnaire-based asthma and affective traits (OR 1.67, 95% CI 1.50-1.86 major depression; OR 1.45, 95% CI 1.30-1.61 anxiety; and OR 1.60, 95% CI 1.40-1.82 high neuroticism). Genetic susceptibility for neuroticism explained the variance in asthma with a dose-response effect; that is, study participants in the highest neuroticism PRS quartile were more likely to have asthma than those in the lowest quartile (OR 1.37, 95% CI 1.17-1.61). Genetic correlations were found between depression and asthma (r g=0.17), but not for anxiety or neuroticism.We conclude that the observed comorbidity between asthma and the affective traits may in part be due to shared genetic influences between asthma and depression (LDSC) and neuroticism (PRS), but not anxiety.