Common obesity risk alleles in childhood attention‐deficit/hyperactivity disorder

Abstract

Children with attention-deficit/hyperactivity disorder (ADHD) have a higher rate of obesity than children without ADHD. Obesity risk alleles may overlap with those relevant for ADHD. We examined whether risk alleles for an increased body mass index (BMI) are associated with ADHD and related quantitative traits (inattention and hyperactivity/impulsivity). We screened 32 obesity risk alleles of single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) for ADHD based on 495 patients and 1,300 population-based controls and performed in silico analyses of the SNPs in an ADHD meta-analysis comprising 2,064 trios, 896 independent cases, and 2,455 controls. In the German sample rs206936 in the NUDT3 gene (nudix; nucleoside diphosphate linked moiety X-type motif 3) was associated with ADHD risk (OR: 1.39; 295 Neuropsychiatric GeneticsP ¼ 3.4 Â 10 À4; P corr ¼ 0.01). In the meta-analysis data we found rs6497416 in the intronic region of the GPRC5B gene (G proteincoupled receptor, family C, group 5, member B; P ¼ 7.2 Â 10 À4 ; P corr ¼ 0.02) as a risk allele for ADHD. GPRC5B belongs to the metabotropic glutamate receptor family, which has been implicated in the etiology of ADHD. In the German sample rs206936 (NUDT3) and rs10938397 in the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) were associated with inattention, whereas markers in the mitogen-activated protein kinase 5 gene (MAP2K5) and in the cell adhesion molecule 2 gene (CADM2) were associated with hyperactivity. In the meta-analysis data, MAP2K5 was associated with inattention, GPRC5B with hyperactivity/impulsivity and inattention and CADM2 with hyperactivity/impulsivity. Our results justify further research on the elucidation of the common genetic background of ADHD and obesity.

Attention-Deficit/Hyperactivity Disorder is Related to Decreased Weight in the Preschool Period and to Increased Rate of Overweight in School-Age Boys

“…Additionally, in this article, we are putting forward hypotheses associating changes in body size over time with changes in psychosocial functioning and stress, whereas the examination did not include assessment of the psychological and social consequences of ADHD. Excessive body weight in patients with ADHD later in life may also be associated with specific genes (Albayrak et al 2013), executive function deficits (Choudry et al 2013), or daytime sleepiness (Cortese et al 2008). The mentioned variables should be taken into account in subsequent researches on growth and the body fat content of children with ADHD.…”

Memory-guided force output is associated with self-reported ADHD symptoms in young adults

“…ADHD is associated with adverse outcomes such as the ability to gain and maintain employment (Kessler et al 2009; Kupper et al 2012), and is associated with an increased risk for substance abuse (Groenman et al 2013; Upadhyaya 2008; Wilens et al 1995), obesity (Albayrak et al 2013; Cortese et al 2008; Nazar et al 2012; Nazar et al 2014), workplace injuries (Breslin and Pole 2009; Hodgkins et al 2011; Swensen et al 2004), and traffic accidents (Barkley and Cox 2007; Barkley et al 1993; Jerome et al 2006a; Jerome et al 2006b; Merkel et al 2013). A majority of diagnosed children have motor deficits, however few studies have examined motor deficits in young adults.…”

Discussing the Putative Role of Obesity-Associated Genes in the Etiopathogenesis of Eating Disorders

“…Interestingly, two subsequent studies have related this SNP to sedentary behavior [169] and attention-deficit/hyperactivity disorder [170], thus establishing a link between this gene and conduct. In addition, genetic variability in this locus has also been associated with vigorous physical activity in adolescents, a feature also present in some ED patients [171].…”