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

Chao-Yu Liu, Tabea Schoeler, Neil M Davies, Hugo Peyre, Kai-Xiang Lim, Edward D Barker, Clare Llewellyn, Frank Dudbridge, Jean-Baptiste Pingault*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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.

Original languageEnglish
Article numberdyaa214
Number of pages14
JournalInternational Journal of Epidemiology
Early online date22 Nov 2020
DOIs
Publication statusE-pub ahead of print - 22 Nov 2020

Keywords

  • ADHD
  • BMI
  • causal inference
  • Mendelian randomization
  • polygenic score
  • twin modelling

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