Maria Carolina Borges1,2, Luciana Tovo-Rodrigues3, Thais Martins-Silva4, Juliana Dos Santos Vaz4,5, Mara Helena Hutz6, Angélica Salatino-Oliveira6, Júlia Pasqualini Genro7, Fernando Pires Hartwig4,1, Carlos Renato Moreira-Maia8, Luis Augusto Rohde8,9. 1. MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK. 2. Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. 3. Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil. luciana.tovo@gmail.com. 4. Postgraduate Program in Epidemiology, Universidade Federal de Pelotas, Pelotas, Brazil. 5. Faculty of Nutrition, Universidade Federal de Pelotas, Pelotas, Brazil. 6. Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 7. Post-Graduate Program in Bioscience, Universidade Fundação de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil. 8. Department of Psychiatry, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 9. National Institute of Developmental Psychiatry for Children and Adolescents, São Paulo, Brazil.
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.
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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