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分析四个与神经发育相关的基因显示,钙黏蛋白 9/10 区域的 rs4307059 多态性与完全性自杀有关。

Analysis of four genes involved in the neurodevelopment shows association of rs4307059 polymorphism in the cadherin 9/10 region with completed suicide.

机构信息

Department of Medical Genetics, Medical University of Warsaw, Warsaw, Poland.

出版信息

Neuropsychobiology. 2012;66(2):134-40. doi: 10.1159/000339559. Epub 2012 Jul 27.

Abstract

BACKGROUND

We hypothesized that DNA variants affecting neurodevelopment such as rs4307059 (CDH10/CDH9), rs930752 (NRXN1), rs6265 (BDNF) or rs10868235 (NTRK2) may predispose to completed suicide.

METHODOLOGY

We used a case-control two-stage approach based on a discovery cohort (557 cases and ∼550 controls) and replication cohort (159 cases and 186 controls). The suicides were ascertained as consecutive cases autopsied at the Department of Forensic Medicine, Medical University of Warsaw, Poland.

RESULTS

In the discovery cohort we found an association between suicide and the CC genotype in the rs4307059 polymorphism (OR 1.64, p = 0.012). The trend for an overrepresentation of the CC homozygotes among suicides was replicated in the second cohort (OR 1.97, p = 0.056). Analysis in the pooled cohorts showed that rs4307059 CC was associated with completed suicide (OR 1.71, p = 0.002) also after Bonferroni correction (p(cor.) = 0.024). In an exploratory search for genotype-phenotype correlation we found that males with the rs4307059 CC genotype committed suicide earlier than those with CT/TT genotypes (p = 0.049).

CONCLUSIONS

The CC genotype of rs4307059 located in the region between CDH9 and CDH10 is associated with completed suicide in a Polish cohort.

摘要

背景

我们假设影响神经发育的 DNA 变体,如 rs4307059(CDH10/CDH9)、rs930752(NRXN1)、rs6265(BDNF)或 rs10868235(NTRK2),可能导致自杀完成。

方法

我们使用基于发现队列(557 例病例和~550 例对照)和复制队列(159 例病例和 186 例对照)的病例对照两阶段方法。自杀是在波兰华沙医科大学法医学系连续进行尸检确定的。

结果

在发现队列中,我们发现 rs4307059 多态性中的 CC 基因型与自杀之间存在关联(OR 1.64,p = 0.012)。在第二个队列中,CC 纯合子在自杀者中过度表达的趋势得到复制(OR 1.97,p = 0.056)。在合并队列的分析中,rs4307059 CC 与完成自杀相关(OR 1.71,p = 0.002),即使在 Bonferroni 校正后(p(cor.) = 0.024)。在探索性的基因型-表型相关性研究中,我们发现携带 rs4307059 CC 基因型的男性比携带 CT/TT 基因型的男性更早自杀(p = 0.049)。

结论

位于 CDH9 和 CDH10 之间区域的 rs4307059 的 CC 基因型与波兰队列中的完成自杀相关。

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