The link between attention deficit hyperactivity disorder (ADHD) symptoms and obesity-related traits: genetic and prenatal explanations

Ville Karhunen,Tuula Hurtig,Marina Evangelou,Verena Zuber,Irma Moilanen,Marjo-Riitta Järvelin,Tom A Bond,Alina Rodriguez

doi:10.1038/s41398-021-01584-4

Abstract

Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with obesity, however, the potential causality between the traits remains unclear. We examined both genetic and prenatal evidence for causality using Mendelian Randomisation (MR) and polygenic risk scores (PRS). We conducted bi-directional MR on ADHD liability and six obesity-related traits using summary statistics from the largest available meta-analyses of genome-wide association studies. We also examined the shared genetic aetiology between ADHD symptoms (inattention and hyperactivity) and body mass index (BMI) by PRS association analysis using longitudinal data from Northern Finland Birth Cohort 1986 (NFBC1986, n = 2984). Lastly, we examined the impact of the prenatal environment by association analysis of maternal pre-pregnancy BMI and offspring ADHD symptoms, adjusted for PRS of both traits, in NFBC1986 dataset. Through MR analyses, we found evidence for bidirectional causality between ADHD liability and obesity-related traits. PRS association analyses showed evidence for genetic overlap between ADHD symptoms and BMI. We found no evidence for a difference between inattention and hyperactivity symptoms, suggesting that neither symptom subtype is driving the association. We found evidence for association between maternal pre-pregnancy BMI and offspring ADHD symptoms after adjusting for both BMI and ADHD PRS (association p-value = 0.027 for inattention, p = 0.008 for hyperactivity). These results are consistent with the hypothesis that the co-occurrence between ADHD and obesity has both genetic and prenatal environmental origins.

Highlights

Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with obesity
Mendelian Randomisation Depending on the trait, the number of independent SNPs available for MR with ADHD liability as the exposure was between nine and 12 (Supplementary Table 2)
The MR results of the effect of ADHD liability on obesity-related traits are summarised in Fig. 2

Summary

Introduction

Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with obesity. There has been a surge of studies investigating this association in recent years, despite some variability in findings, the consensus is that the association is well replicated, yet puzzling [1,2,3,4]. Inattention and hyperactivity, the core symptom subtypes of ADHD, interfere with development and functioning [6], even at levels below the clinical threshold [7], and are linked to a negative developmental trajectory [8], whereas obesity is a risk factor for all-cause mortality [9]. Our goal is to examine the evidence for causality, both genetic and prenatal, that may explain the ADHD-overweight/obesity association using Mendelian Randomisation (MR) and polygenic risk scores (PRS)

Objectives

Methods

Results

Discussion

Conclusion