Both prenatal maternal health and genetic factors can explain the previously unexplained association between attention deficit/hyperactivity disorder (ADHD) and obesity.
A team, led by Ville Karhunen, Department of Epidemiology and Biostatistics, Imperial College London, examined the genetic and prenatal evidence for causality between obesity and ADHD using Mendelian Randomization (MR) and polygenic risk scores (PRS).
While ADHD often is a comorbidity with obesity, the cause of the co-occurring disorders is unclear. In recent years, a plethora of studies have attempted to shed light on this association.
“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,” the authors wrote. “Together, the double burden of both conditions accounts for nearly a two-fold increase in the cost of care.”
In the study, the investigators used summary statistics from the largest available meta-analyses of genome-wide association trials to conduct a bi-directional Mendelian Randomization on ADHD liability and 6 obesity-related traits. The investigators also looked at the shared genetic etiology between ADHD symptoms, mainly inattention and hyperactivity, and body mass index (BMI).
They did so by using polygenic risk score association analysis from longitudinal data derived from 2984 participants in the Northern Finland Birth Cohort 1986.
Overall, the investigators used summary statistics for ADHD liability for 55,374 individuals—20,183 cases and 35,191 controls—from 12 cohorts.
ADHD symptoms were rated by mothers and teachers at 7 and 8 years, respectively.
Finally, the team identified the impact of the prenatal environment by association analysis of maternal pre-pregnancy BMI and offspring ADHD symptoms. The data was adjusted for PRS of both trains the birth cohort dataset.
After conducting the Mendelian Randomization analysis, the investigators found bidirectional causality between ADHD liability and obesity-related traits. Polygenic risk scores also showed a genetic overlap between ADHD symptoms and BMI.
On the other hand, there was no evidence for a difference between inattention and hyperactivity symptoms. This might suggest that neither symptom subtype is driving the link between ADHD and obesity.
They did find evidence of the association between maternal BMI prior to pregnancy and offspring ADHD symptoms after the investigators adjusted for both BMI and ADHD polygenetic risk scores (association P = 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,” the authors wrote. “Our results bolster the suggested bidirectional association derived from evidence across observational studies.”
Some of the reasons for this causal link include ADHD leading to higher obesity risk because of abnormal functioning of the dopamine pathway that leads to decreased physical activity and increased sedentary lifestyle.
Obesity is also known to trigger systemic chronic inflammation, which impacts brain functions with ADHD-type symptoms.
The study, “The link between attention deficit hyperactivity disorder (ADHD) symptoms and obesity-related traits: genetic and prenatal explanations,” was published online in Translational Psychiatry.