title: CDH13 is associated with working memory performance in attention deficit/hyperactivity disorder.
abstract: Different analytic strategies, including linkage, association and meta-analysis support a role of CDH13 in the susceptibility to attention deficit/hyperactivity disorder (ADHD). CDH13 codes for cadherin 13 (or H-cadherin), which is a member of a family of calcium-dependent cell-cell adhesion proteins and a regulator of neural cell growth. We tested the association between CDH13 on three executive functioning tasks that are promising endophenotypes of ADHD. An adjusted linear regression analysis was performed in 190 ADHD-affected Dutch probands of the IMAGE project. Three executive functions were examined: inhibition, verbal and visuo-spatial working memory (WM). We tested 2632 single nucleotide polymorphisms (SNPs) within CDH13 and 20 kb up- and downstream of the gene (capturing regulatory sequences). To adjust for multiple testing within the gene, we applied stringent permutation steps. Intronic SNP rs11150556 is associated with performance on the Verbal WM task. No other SNP showed gene-wide significance with any of the analyzed traits, but a 72-kb SNP block located 446 kb upstream of SNP rs111500556 showed suggestive evidence for association (P-value range 1.20E-03 to 1.73E-04) with performance in the same Verbal WM task. This study is the first to examine CDH13 and neurocognitive functioning. The mechanisms underlying the associations between CDH13 and the clinical phenotype of ADHD and verbal WM are still unknown. As such, our study may be viewed as exploratory, with the results presented providing interesting hypotheses for further testing.
authors.affiliation: Department of Psychiatry (966), Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Arias-Vásquez
authors.forename: M E
authors.initials: ME
authors.lastname: Altink
authors.forename: N N J
authors.initials: NN
authors.lastname: Rommelse
authors.forename: D I E
authors.initials: DI
authors.lastname: Slaats-Willemse
authors.forename: C J M
authors.initials: CJ
authors.lastname: Buschgens
authors.forename: E A
authors.initials: EA
authors.lastname: Fliers
authors.forename: S V
authors.initials: SV
authors.lastname: Faraone
authors.forename: J A
authors.initials: JA
authors.lastname: Sergeant
authors.forename: J
authors.initials: J
authors.lastname: Oosterlaan
authors.forename: B
authors.initials: B
authors.lastname: Franke
authors.forename: J K
authors.initials: JK
authors.lastname: Buitelaar
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology*; D015820:Cadherins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007266:Inhibition, Psychological; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D009426:Netherlands; D009483:Neuropsychological Tests; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011597:Psychomotor Performance / Q000502:physiology*; D012044:Regression Analysis; D013028:Space Perception / Q000502:physiology; D014796:Visual Perception / Q000502:physiology; D014888:Wechsler Scales
chemical_list: D015820:Cadherins; C099972:H-cadherin; D004247:DNA