title: 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; P = 3.4 × 10(-4) ; Pcorr  = 0.01). In the meta-analysis data we found rs6497416 in the intronic region of the GPRC5B gene (G protein-coupled receptor, family C, group 5, member B; P = 7.2 × 10(-4) ; Pcorr  = 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.
authors.affiliation: Department of Child and Adolescent Psychiatry, Psychotherapy and Psychosomatics, LVR Klinikum Essen, University of Duisburg-Essen, D-45147 Essen, Germany. oezguer.albayrak@uni-due.de
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Albayrak
authors.forename: Carolin
authors.initials: C
authors.lastname: Pütter
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Volckmar
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
authors.forename: Per
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Neale
authors.forename: Beate
authors.initials: B
authors.lastname: Herpertz-Dahlmann
authors.forename: Gerd
authors.initials: G
authors.lastname: Lehmkuhl
authors.forename: Judith
authors.initials: J
authors.lastname: Sinzig
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Renner
authors.forename: Marcel
authors.initials: M
authors.lastname: Romanos
authors.forename: Andreas
authors.initials: A
authors.lastname: Warnke
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Benno G
authors.initials: BG
authors.lastname: Schimmelmann
authors.forename: André
authors.initials: A
authors.lastname: Scherag
authors.forename: Johannes
authors.initials: J
authors.lastname: Hebebrand
authors.forename: Anke
authors.initials: A
authors.lastname: Hinney
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics*; D015992:Body Mass Index; D002648:Child; D020022:Genetic Predisposition to Disease; D006801:Humans; D009765:Obesity / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide