Attention-deficit hyperactivity disorder (ADHD), one of the most common neurodevelopmental disorders in childhood and adolescence, is associated with obesity in observational studies. However, it is unclear whether ADHD contributes to, results from or is merely correlated with obesity. This study evaluates the presence and direction of a causal effect between ADHD and obesity.
We performed a bidirectional two-sample Mendelian randomization using summary data from consortia of genome-wide association studies to investigate if ADHD (N = 55,374) has a causal effect on body mass index (BMI) in childhood (N = 35,668) and adulthood (N = 322,154–500,000), and vice-versa. The main analysis was performed using the inverse variance weighted (IVW) method. As sensitivity analyses, we used other Mendelian randomization methods that are more robust to horizontal pleiotropy (i.e., MR-Egger, weighted mode, and penalized weighted median estimators), as well as stratified the analysis by the putative mechanisms of genetic instruments (i.e., pathways involved or not in neurological processes).
The IVW method indicated a positive causal effect of BMI on ADHD: β = 0.324 (95% CI 0.198 to 0.449, p < 0.001; expressed as change in ln(odds ratio) of ADHD per each additional SD unit of BMI). IVW estimates were directionally consistent with other methods. On the other hand, we did not find consistent evidence for a causal effect of ADHD genetic liability on BMI.
The results suggested that higher BMI increases the risk of developing ADHD, but not the other way around.
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TMS received a scholarship for a PhD’s degree from the Coordination of Improvement of Higher Level Personnel (CAPES). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. MCB is supported by a UK Medical Research Council (MRC) Skills Development Fellowship (MR/P014054/1). FPH is supported by a Brazilian National Council for Scientific and Technological Development (CNPq) postdoctoral fellowship. We wish to thank Vanessa Rodrigues Paixão-Côrtes for her assistance with the figures editing.