Epidemiology and population health

Assessing causality in the association between attention-deficit/hyperactivity disorder and obesity: a Mendelian randomization study

Abstract

Background/Objectives

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.

Subjects/Methods

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).

Results

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.

Conclusions

The results suggested that higher BMI increases the risk of developing ADHD, but not the other way around.

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Acknowledgements

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.

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Correspondence to Luciana Tovo-Rodrigues.

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Conflict of interest

LAR has been a member of the speakers’ bureau/advisory board and/or acted as a consultant for Eli-Lilly, Janssen-Cilag, Medice, Novartis and Shire in the last 3 years. He receives authorship royalties from Oxford Press and ArtMed. He has also received travel awards from Shire for his participation in the 2018 APA meetings and from Novartis to take part of the 2016 AACAP meeting. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by him received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Janssen - Cilag, Novartis, and Shire. The remaining authors declare that they have no conflict of interest.

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Martins-Silva, T., Vaz, J.d.S., Hutz, M.H. et al. Assessing causality in the association between attention-deficit/hyperactivity disorder and obesity: a Mendelian randomization study. Int J Obes 43, 2500–2508 (2019). https://doi.org/10.1038/s41366-019-0346-8

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