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Are there causal relationships between attention-deficit/hyperactivity disorder and body mass index? Evidence from multiple genetically informed designs

Liu, C-Y; Schoeler, T; Davies, NM; Peyre, H; Lim, K-X; Barker, ED; Llewellyn, C; ... Pingault, J-B; + view all (2021) Are there causal relationships between attention-deficit/hyperactivity disorder and body mass index? Evidence from multiple genetically informed designs. International Journal of Epidemiology , 50 (2) pp. 496-509. 10.1093/ije/dyaa214. Green open access

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Abstract

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and body mass index (BMI) are associated. However, it remains unclear whether this association reflects causal relationships in either direction or confounding. Here, we implemented genetically informed methods to examine bidirectional causality and potential confounding. METHODS: Three genetically informed methods were employed: (i) cross-lagged twin-differences analyses to assess bidirectional effects of ADHD symptoms and BMI at ages 8, 12, 14 and 16 years in 2386 pairs of monozygotic twins from the Twins Early Development Study (TEDS); (ii) within- and between-family ADHD and BMI polygenic score (PS) analyses in 3320 pairs of dizygotic TEDS twins; and (iii) two-sample bidirectional Mendelian randomization (MR) using summary statistics from genome-wide association studies (GWAS) on ADHD (N = 55,374) and BMI (N = 806,834). RESULTS: Mixed results were obtained across the three methods. Twin-difference analyses provided little support for cross-lagged associations between ADHD symptoms and BMI over time. PS analyses were consistent with bidirectional relationships between ADHD and BMI, with plausible time-varying effects from childhood to adolescence. MR findings also suggested bidirectional causal effects between ADHD and BMI. Multivariable MR indicated the presence of substantial confounding in bidirectional relationships. CONCLUSIONS: The three methods converged to highlight multiple sources of confounding in the association between ADHD and BMI. PS and MR analyses suggested plausible causal relationships in both directions. Possible explanations for mixed causal findings across methods are discussed.

Type: Article
Title: Are there causal relationships between attention-deficit/hyperactivity disorder and body mass index? Evidence from multiple genetically informed designs
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/ije/dyaa214
Publisher version: http://dx.doi.org/10.1093/ije/dyaa214
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: ADHD, BMI, Mendelian randomization, causal inference, polygenic score, twin modelling
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Clinical, Edu and Hlth Psychology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Behavioural Science and Health
URI: https://discovery.ucl.ac.uk/id/eprint/10116487
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