Common and Unique Genetic Background between Attention-Deficit/Hyperactivity Disorder and Excessive Body Weight

Abstract

Comorbidity studies show that children with ADHD have a higher risk of being overweight and obese than healthy children. This study aimed to assess the genetic alternations that differ between and are shared by ADHD and excessive body weight (EBW). The sample consisted of 743 Polish children aged between 6 and 17 years. We analyzed a unique set of genes and polymorphisms selected for ADHD and/or obesity based on gene prioritization tools. Polymorphisms in the KCNIP1, SLC1A3, MTHFR, ADRA2A, and SLC6A2 genes proved to be associated with the risk of ADHD in the studied population. The COMT gene polymorphism was one that specifically increased the risk of EBW in the ADHD group. Using the whole-exome sequencing technique, we have shown that the ADHD group contains rare and protein-truncating variants in the FBXL17, DBH, MTHFR, PCDH7, RSPH3, SPTBN1, and TNRC6C genes. In turn, variants in the ADRA2A, DYNC1H1, MAP1A, SEMA6D, and ZNF536 genes were specific for ADHD with EBW. In this way, we confirmed, at the molecular level, the existence of genes specifically predisposing to EBW in ADHD patients, which are associated with the biological pathways involved in the regulation of the reward system, intestinal microbiome, and muscle metabolism.

Appetitive and psychological phenotypes of pediatric patients with obesity

“…This theory is supported by positive associations and overlapping genetic pathways between reward response, ADHD and obesity. 29,30 It could be hypothesized that patients with the Hedonic Impulsive phenotype may respond especially well to obesity treatments that target impulsivity and reward-based eating like psychostimulants and naltrexone/bupropion, 31 respectively. In addition, behaviorally focused treatments targeting cue exposure to reduce food reward responsivity may also be effective.…”

“…One theory explaining the association between obesity and ADHD is termed ‘reward sensitivity’, suggesting that individuals with ADHD are hypersensitive to reward and that this ‘hedonic’ drive to eat especially palatable foods is greater than the person's capacity for inhibition of such behaviours. This theory is supported by positive associations and overlapping genetic pathways between reward response, ADHD and obesity 29,30 . It could be hypothesized that patients with the Hedonic Impulsive phenotype may respond especially well to obesity treatments that target impulsivity and reward‐based eating like psychostimulants and naltrexone/bupropion, 31 respectively.…”

Whole genome sequencing of mouse lines divergently selected for fatness (FLI) and leanness (FHI) revealed several genetic variants as candidates for novel obesity genes

“…Methylation of PCED1A (PC-esterase domain containing 1 A) in human was affected by dietary fat quality (Voisin et al 2015 ), and PCED1A might affect cellular rearrangement during adipocyte expansion in muscles (Silva-Vignato et al 2022 ). Transcription factor ZFP536 (zinc finger protein 536) is involved in neurone differentiation (Qin et al 2009 ) and was associated with both Attention-Deficit/Hyperactivity Disorder (ADHD) and excessive body weight (Dmitrzak-Weglarz et al 2021 ), linking psychological disorders with obesity.…”

Relationship of weight-adjusted waist index and developmental disabilities in children 6 to 17 years of age: a cross-sectional study

“…However, there have been no studies of childhood DDs related to the WWI. It has been demonstrated in previous studies that DDs are associated with childhood overweight and obesity ( 19 – 21 ). However, the correlation of the WWI with the prevalence of DDs has not been studied.…”