title: SPOCK3, a risk gene for adult ADHD and personality disorders.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is the most frequent psychiatric disorder in children, where it displays a global prevalence of 5 %. In up to 50 % of the cases, ADHD may persist into adulthood (aADHD), where it is often comorbid with personality disorders. Due to a potentially heritable nature of this comorbidity, we hypothesized that their genetic framework may contain common risk-modifying genes. SPOCK3, a poorly characterized, putatively Ca(2+)-binding extracellular heparan/chondroitin sulfate proteoglycan gene encoded by the human chromosomal region 4q32.3, was found to be associated with polymorphisms among the top ranks in a genome-wide association study (GWAS) on ADHD and a pooled GWAS on personality disorder (PD). We therefore genotyped 48 single nucleotide polymorphisms (SNPs) representative of the SPOCK3 gene region in 1,790 individuals (n aADHD = 624, n PD = 630, n controls = 536). In this analysis, we found two SNPs to be nominally associated with aADHD (rs7689440, rs897511) and four PD-associated SNPs (rs7689440, rs897511, rs17052671 and rs1485318); the latter even reached marginal significance after rigorous Bonferroni correction. Bioinformatics tools predicted a possible influence of rs1485318 on transcription factor binding, whereas the other candidate SNPs may have effects on alternative splicing. Our results suggest that SPOCK3 may modify the genetic risk for ADHD and PD; further studies are, however, needed to identify the underlying mechanisms.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany, Weber_H2@klinik.uni-wuerzburg.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Weber
authors.forename: Claus-Jürgen
authors.initials: CJ
authors.lastname: Scholz
authors.forename: Christian P
authors.initials: CP
authors.lastname: Jacob
authors.forename: Julia
authors.initials: J
authors.lastname: Heupel
authors.forename: Sarah
authors.initials: S
authors.lastname: Kittel-Schneider
authors.forename: Angelika
authors.initials: A
authors.lastname: Erhardt
authors.forename: Susanne
authors.initials: S
authors.lastname: Hempel
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schmidt
authors.forename: Tilman
authors.initials: T
authors.lastname: Kiel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gessner
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010554:Personality Disorders / Q000235:genetics*; D010555:Personality Inventory; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011509:Proteoglycans / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors
chemical_list: D011509:Proteoglycans; C504409:SPOCK3 protein, human