KCNIP4 as a candidate gene for personality disorders and adult ADHD

• Published in: European neuropsychopharmacology Vol. 23; no. 6; pp. 436 - 447
• Main Authors: Weißflog, Lena, Scholz, Claus-Jürgen, Jacob, Christian P, Nguyen, Thuy Trang, Zamzow, Karin, Groß-Lesch, Silke, Renner, Tobias J, Romanos, Marcel, Rujescu, Dan, Walitza, Susanne, Kneitz, Susanne, Lesch, Klaus-Peter, Reif, Andreas
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2013
• Subjects: ADHD; Adult; Association study; Attention Deficit Disorder with Hyperactivity - genetics; Attention Deficit Disorder with Hyperactivity - metabolism; Diagnostic and Statistical Manual of Mental Disorders; Female; Genetic Loci; Genetic Predisposition to Disease; Genome-wide association; Genome-Wide Association Study; Germany; Humans; Internal Medicine; Kv channel interacting protein; Kv Channel-Interacting Proteins - genetics; Kv Channel-Interacting Proteins - metabolism; Male; Middle Aged; Personality disorders; Personality Disorders - genetics; Personality Disorders - metabolism; Polymorphism, Single Nucleotide; Psychiatry; Germany; Association study; ADHD; Genome-wide association; Kv channel interacting protein; Personality disorders
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2012.07.017

Abstract Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder in children with striking persistence into adulthood and a high co-morbidity with other psychiatric disorders, including personality disorders (PD). The 4p15.31 region was shown to be associated with ADHD in several genome wide association studies (GWAS). In the present study we also report association of the 4p15.31 locus with Cluster B and Cluster C PD as identified by a pooled genome-wide association study in 400 individuals suffering from PD. The gene coding for the Kv channel-interacting protein 4 ( KCNIP4 ) is located in this region. KCNIP4 is an interaction partner of presenilin and plays a role in a negative feedback loop in the Wnt/β-catenin pathway. Thus, we reasoned it to be a promising candidate gene for ADHD as well as for PD. To clarify the role of KCNIP4 in those disorders, we conducted candidate gene based association studies in 594 patients suffering from adult ADHD and 630 PD patients as compared to 974 healthy control individuals. In the adult ADHD sample, six single markers and one haplotype block revealed to be associated with disease ( p values from 0.0079 to 0.049). Seven markers within the KCNIP4 gene showed an association with PD ( p values from 0.0043 to 0.0437). The results of these studies suggest a role of KCNIP4 in the etiology of ADHD, PD and other co-morbid disorders.