Do ADHD-impulsivity and BMI have shared polygenic and neural correlates?

Abstract

There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r=0.10,n=874,p=0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r=0.17,n=874,p=6.5 × 10−6FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b=0.006, 90% CIs=0.001, 0.019) and BMI (b=0.009, 90% CIs=0.001, 0.025) via the neuroimaging substrate. The BMI PRS associated with BMI (b=0.014, 95% CIs=0.003, 0.033) and impulsivity symptoms (b=0.009, 90% CIs=0.001, 0.025) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.