The role of ASTN2 variants in childhood and adult ADHD, comorbid disorders and associated personality traits

• Published in: Journal of Neural Transmission Vol. 123; no. 8; pp. 849 - 858
• Main Authors: Freitag, Christine M., Lempp, Thomas, Nguyen, T. Trang, Jacob, Christian P., Weissflog, Lena, Romanos, Marcel, Renner, Tobias J., Walitza, Susanne, Warnke, Andreas, Rujescu, Dan, Lesch, Klaus-Peter, Reif, Andreas
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.08.2016
• Subjects: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity - genetics; Attention Deficit Disorder with Hyperactivity - psychology; Case-Control Studies; Child; Female; Genetic Association Studies; Genetic Predisposition to Disease - genetics; Glycoproteins - genetics; Humans; Male; Medicine; Medicine & Public Health; Nerve Tissue Proteins - genetics; Neurology; Neurosciences; Parents - psychology; Personality; Personality Disorders - genetics; Polymorphism, Single Nucleotide - genetics; Psychiatry; Psychiatry and Preclinical Psychiatric Studies - Original Article; Young Adult; Astrotactin 2; Attention-deficit/hyperactivity disorder; Anxiety disorder; Personality traits; Comorbid disorders
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-016-1553-2

Previous linkage and genome wide association (GWA) studies in ADHD indicated astrotactin 2 ( ASTN2 ) as a candidate gene for attention-deficit/hyperactivity disorder (ADHD). ASTN2 plays a key role in glial-guided neuronal migration. To investigate whether common variants in ASTN2 contribute to ADHD disorder risk, we tested 63 SNPs spanning ASTN2 for association with ADHD and specific comorbid disorders in two samples: 171 families of children with ADHD and their parents ( N  = 592), and an adult sample comprising 604 adult ADHD cases and 974 controls. The C-allele of rs12376789 in ASTN2 nominally increased the risk for ADHD in the trio sample ( p  = 0.025). This was not observed in the adult case–control sample alone, but retained in the combined sample (nominal p  = 0.030). Several other SNPs showed nominally significant association with comorbid disorders, especially anxiety disorder, in the childhood and adult ADHD samples. Some ASTN2 variants were nominally associated with personality traits in the adult ADHD sample and overlapped with risk alleles for comorbid disorders in childhood. None of the findings survived correction for multiple testing, thus, results do not support a major role of common variants in ASTN2 in the pathogenesis of ADHD, its comorbid disorders or ADHD associated personality traits.