Attention Deficit Hyperactivity Disorder and Obesity: The Weight of Shared Genetic Risk Factors

Abstract

Apart from being highly comorbid with other psychiatric disorders, ADHD is also associated with the occurrence of certain somatic conditions. In particular, the relationship between ADHD and obesity has been receiving growing attention. Meta-analytic studies show increased prevalence of obesity in ADHD patients as well as higher rates of ADHD in individuals with obesity. However, the role of specific behavioural, neuropsychological, and genetic factors contributing to the development of such comorbidity deserves further investigation. Possible mechanisms underlying the comorbidity between ADHD and obesity have been suggested, including the dopaminergic neurotransmission and the circadian rhythm systems, which have both been associated with each condition individually. The recent success of ADHD GWAS and great increase in sample size enable us to explore the role of common genetic variants shared by these frequently co-occurring conditions. The findings that will be presented derive from a series of analyses, which take both hypothesis-free and hypothesis-driven approaches. We first examine the potential of polygenic risk scores (PRS) to predict ADHD symptoms and obesity-related traits in the general population. As discovery samples, this study makes use of the summary statistics from the latest ADHD GWAS from the Psychiatric Genomics Consortium(PGC)-iPSYCH collaboration, the first large-scale adult ADHD GWAS from the International Multicentre persistent ADHD CollaboraTion (IMpACT), and the latest publicly available GWAS on body mass index (BMI), a trait closely-related to obesity (Locke et al., 2015 - GIANT consortium). Our initial results, using as target sample the Dutch cohort from the Nijmegen Biomedical Study (NBS; N=~3200 adults), show that ADHD-based PRS is associated with BMI (P=8.7x10-6, R2=0.59%) and with overweight/obesity (P=0.007, R2=0.3%); on the other hand, BMI-based PRS is associated with the presence of ADHD symptoms in childhood (P=0.007; R2=0.37%). The contribution of candidate pathways will also be discussed, where we examine the association of genes related to the dopaminergic and circadian rhythm systems with ADHD and obesity-related traits by conducting gene-set analyses using the aforementioned GWAS results. Finally, we will explore possible mediating roles of behavioural and neuropsychological traits and neuroimaging measures on the associations identified in more phenotypically characterized clinical and population samples. The great impact both ADHD and obesity have on an individuals’ life, as well as on society as a whole, emphasize the importance of pursuing a better understanding of the underlying mechanisms contributing to the co-occurrence of these phenotypes. A clearer picture of the factors involved in such comorbidity, as well as their effects on the general population, may provide relevant insights in terms of early treatment or even prevention guidelines.