Supplementary Material for: Analysis of Four Genes Involved in the Neurodevelopment Shows Association of rs4307059 Polymorphism in the Cadherin 9/10 Region with Completed Suicide

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 (pcor. = 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.研究背景：本研究提出假设，可影响神经发育的DNA变异，如rs4307059（CDH10/CDH9）、rs930752（NRXN1）、rs6265（BDNF）及rs10868235（NTRK2），可能增加个体完成自杀的易感性。研究方法：本研究采用两阶段病例-对照研究方案，以发现队列（557例病例、约550例对照）与验证队列（159例病例、186例对照）为研究基础。本研究纳入的自杀死亡病例均为波兰华沙医科大学法医学系连续收检、经尸检确认的病例。研究结果：在发现队列中，我们观察到rs4307059多态性位点的CC基因型与自杀死亡存在关联（比值比OR=1.64，p=0.012）。自杀死亡者中CC纯合子比例偏高的趋势在验证队列中得到重复（OR=1.97，p=0.056）。合并双队列进行分析显示，经邦弗朗尼校正（Bonferroni correction）后，rs4307059 CC基因型仍与自杀死亡存在关联（OR=1.71，p=0.002，校正后p值p_cor.=0.024）。在基因型-表型关联的探索性分析中，我们发现携带rs4307059 CC基因型的男性，其自杀死亡年龄早于携带CT/TT基因型的男性（p=0.049）。研究结论：位于CDH9与CDH10基因间区域的rs4307059位点CC基因型，在波兰人群队列中与自杀死亡存在关联。