KCNIP4 as a candidate gene for personality disorders and adult ADHD

Lena Weissflog*, Claus-Juergen Scholz, Christian P. Jacob, Thuy Trang Nguyen, Karin Zamzow, Silke Gross-Lesch, Tobias J. Renner, Marcel Romanos, Dan Rujescu, Susanne Walitza, Susanne Kneitz, Klaus-Peter Lesch, Andreas Reif

*Corresponding author for this work

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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/?-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. Elsevier B.V. and ECNP. All rights reserved.
Original languageEnglish
Pages (from-to)436-447
JournalEuropean Neuropsychopharmacology
Volume23
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • ADHD
  • Personality disorders
  • Genome-wide association
  • Kv channel interacting protein
  • Association study

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