Asthma and attention deficit hyperactivity disorder in childhood: birth cohort study

<bold>Background:</bold> The positive association between asthma and attention deficit hyperactivity disorder (ADHD) has not been adequately explained. <bold>Aims:</bold> To investigate whether it is causal or whether shared genetics and/or shared early-life risk factors (RFs) explain the link. <bold>Methods:</bold> We used 2-sample Mendelian Randomization (MR) to test the causal relationship between asthma and ADHD. In the Avon Longitudinal Study of Parents and Children (ALSPAC), we defined doctor-diagnosed asthma, its endotypes according to atopy determined by skin-prick tests, and ADHD using the Strengths and Difficulties Questionnaire, all at seven years of age. We explored whether the asthma-ADHD association was attenuated when controlling for an extensive number of early-life RFs. Child polygenic risk scores (PRSs) for asthma and ADHD were calculated using published genome-wide association studies across 7 P-value thresholds (<5×10−08 to <0.5). <bold>Results:</bold> We found little evidence of a causal effect between asthma and ADHD in both directions. In ALSPAC, asthma (OR 1.35, 95% CI 1.10−1.65), particularly non-atopic asthma (1.51, 1.09−2.08), was associated with ADHD in crude models, while atopic asthma was not (1.00, 0.69−1.45). These associations were largely attenuated after adjusting for 14 shared early-life risk factors (1.15, 0.93−1.42 for asthma and 1.24, 0.88−1.75 for non-atopic asthma). Asthma PRSs were not associated with ADHD at any P-value threshold, whereas ADHD PRSs were associated with asthma and non-atopic asthma at most thresholds. <bold>Conclusions:</bold> The association between asthma and ADHD in childhood is unlikely to be causal and is largely explained by shared early-life RFs, with some evidence for a shared genetic background.