Department of Psychiatry, ADHD Clinical Research Network, Molecular Psychiatry Laboratory of Translational Neuroscience; Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany.
Eur Neuropsychopharmacol. 2013 Jun;23(6):436-47. doi: 10.1016/j.euroneuro.2012.07.017. Epub 2012 Sep 14.
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.
注意缺陷多动障碍（ADHD）是一种儿童神经发育障碍，在成年后具有明显的持续性，并与其他精神障碍（包括人格障碍）高度共病。几项全基因组关联研究（GWAS）表明，4p15.31 区域与 ADHD 有关。在本研究中，我们还报告了 4p15.31 位点与 400 名患有 PD 的个体的全基因组关联研究中确定的 B 群和 C 群 PD 的关联。编码钾通道相互作用蛋白 4（KCNIP4）的基因位于该区域。KCNIP4 是早老素的相互作用伙伴，在 Wnt/β-catenin 途径的负反馈环中发挥作用。因此，我们认为它是 ADHD 以及 PD 的一个有前途的候选基因。为了阐明 KCNIP4 在这些疾病中的作用，我们在 594 名成年 ADHD 患者和 630 名 PD 患者中进行了基于候选基因的关联研究，与 974 名健康对照个体进行了比较。在成年 ADHD 样本中，六个单标记和一个单倍型块与疾病相关（p 值从 0.0079 到 0.049）。KCNIP4 基因内的七个标记与 PD 相关（p 值从 0.0043 到 0.0437）。这些研究的结果表明 KCNIP4 在 ADHD、PD 和其他共病障碍的发病机制中起作用。
