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

• Published in: International Journal of Obesity Vol. 43; no. 12; pp. 2500 - 2508
• Main Authors: Martins-Silva, Thais, Vaz, Juliana dos Santos, Hutz, Mara Helena, Salatino-Oliveira, Angélica, Genro, Júlia Pasqualini, Hartwig, Fernando Pires, Moreira-Maia, Carlos Renato, Rohde, Luis Augusto, Borges, Maria Carolina, Tovo-Rodrigues, Luciana
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2019; Nature Publishing Group
• Subjects: 45; 45/43; 631/208/135; 692/499; Adolescents; Adult; Attention Deficit Disorder with Hyperactivity - complications; Attention Deficit Disorder with Hyperactivity - epidemiology; Attention deficit hyperactivity disorder; Body Mass Index; Body size; Causality; Child; Child, Preschool; Children; Consortia; Correlation analysis; Epidemiology; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Health Promotion and Disease Prevention; Humans; Hyperactivity; Internal Medicine; Liability; Medicine; Medicine & Public Health; Mendelian Randomization Analysis; Metabolic Diseases; Neurodevelopmental disorders; Obesity; Obesity - complications; Obesity - epidemiology; Observational studies; Pleiotropy; Public Health; Randomization; Sensitivity analysis; Whites; Brazil
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-019-0346-8

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.