Dataset Information

DIRAS2 is associated with adult ADHD, related traits, and co-morbid disorders.

ABSTRACT: Several linkage analyses implicated the chromosome 9q22 region in attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disease with remarkable persistence into adulthood. This locus contains the brain-expressed GTP-binding RAS-like 2 gene (DIRAS2) thought to regulate neurogenesis. As DIRAS2 is a positional and functional ADHD candidate gene, we conducted an association study in 600 patients suffering from adult ADHD (aADHD) and 420 controls. Replication samples consisted of 1035 aADHD patients and 1381 controls, as well as 166 families with a child affected from childhood ADHD. Given the high degree of co-morbidity with ADHD, we also investigated patients suffering from bipolar disorder (BD) (n=336) or personality disorders (PDs) (n=622). Twelve single-nucleotide polymorphisms (SNPs) covering the structural gene and the transcriptional control region of DIRAS2 were analyzed. Four SNPs and two haplotype blocks showed evidence of association with ADHD, with nominal p-values ranging from p=0.006 to p=0.05. In the adult replication samples, we obtained a consistent effect of rs1412005 and of a risk haplotype containing the promoter region (p=0.026). Meta-analysis resulted in a significant common OR of 1.12 (p=0.04) for rs1412005 and confirmed association with the promoter risk haplotype (OR=1.45, p=0.0003). Subsequent analysis in nuclear families with childhood ADHD again showed an association of the promoter haplotype block (p=0.02). rs1412005 also increased risk toward BD (p=0.026) and cluster B PD (p=0.031). Additional SNPs showed association with personality scores (p=0.008-0.048). Converging lines of evidence implicate genetic variance in the promoter region of DIRAS2 in the etiology of ADHD and co-morbid impulsive disorders.

SUBMITTER: Reif A

PROVIDER: S-EPMC3176568 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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DIRAS2 is associated with adult ADHD, related traits, and co-morbid disorders.

Reif Andreas A Nguyen T Trang TT Weissflog Lena L Jacob Christian P CP Romanos Marcel M Renner Tobias J TJ Buttenschon Henriette N HN Kittel-Schneider Sarah S Gessner Alexandra A Weber Heike H Neuner Maria M Gross-Lesch Silke S Zamzow Karin K Kreiker Susanne S Walitza Susanne S Meyer Jobst J Freitag Christine M CM Bosch Rosa R Casas Miquel M Gómez Nuria N Ribasès Marta M Bayès Mónica M Buitelaar Jan K JK Kiemeney Lambertus A L M LA Kooij J J Sandra JJ Kan Cees C CC Hoogman Martine M Johansson Stefan S Jacobsen Kaya K KK Knappskog Per M PM Fasmer Ole B OB Asherson Phil P Warnke Andreas A Grabe Hans-Jörgen HJ Mahler Jessie J Teumer Alexander A Völzke Henry H Mors Ole N ON Schäfer Helmut H Ramos-Quiroga Josep Antoni JA Cormand Bru B Haavik Jan J Franke Barbara B Lesch Klaus-Peter KP

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20110713 11

Several linkage analyses implicated the chromosome 9q22 region in attention deficit/hyperactivity disorder (ADHD), a neurodevelopmental disease with remarkable persistence into adulthood. This locus contains the brain-expressed GTP-binding RAS-like 2 gene (DIRAS2) thought to regulate neurogenesis. As DIRAS2 is a positional and functional ADHD candidate gene, we conducted an association study in 600 patients suffering from adult ADHD (aADHD) and 420 controls. Replication samples consisted of 1035 ...[more]

PMID: 21750579

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Dataset Information

DIRAS2 is associated with adult ADHD, related traits, and co-morbid disorders.

Publications

DIRAS2 is associated with adult ADHD, related traits, and co-morbid disorders.

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