A common cdh13 variant is associated with low agreeableness and neural responses to working memory tasks in adhd

Abstract

The cell–cell signaling gene CDH13 is associated with a wide spectrum of neuropsychiat-ric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depres-sion. CDH13 regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of CDH13 on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the CDH13 gene in humans is sparse. Therefore, we tested for association of a functional intronic CDH13 SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy con-trols. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-de-pendent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The Rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was signif-icantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect lim-ited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited signifi-cantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of CDH13 is associated with personality traits and impacts neural processing during working memory tasks. Thus, CDH13 might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.