Background Genetic diathesis of suicide is supported by family and twin studies. Few candidate gene pathways are known, but does not explain fully the complexity of suicide genetic risk. Recent investigations opting for Genome-Wide Association Studies (GWAS) resulted in finding additional targets, but replication remained a challenge. In this respect small isolated population approach in several complex disease phenotypes is found encouraging. The present study is an attempt to re-test some of the reported significant SNPs for suicide among a small historical high- risk isolated population from Northeast India. Methods Two hundred ten cases (inclusive of depressed, suicide attempter and depressed + suicide attempter) and 249 controls were considered in the present study which were evaluated for the psychiatric parameters. Sixteen reported significant SNPs for suicide behaviour were re-tested using association approach under various genetic models. Networking by GeneMANIA tool was used for function prediction of the associated genes. Results Seven SNPs (of 6 genes) remained significant in different genetic models. On networking genes with significant SNPs IL7, RHEB, CTNN3, KCNIP4 , ARFGEF3 are found in interaction with already known candidate gene pathways while SNP rs1109089 (RHEB ) gained further support from earlier expression studies. NUGGC gene is in complete isolation. Conclusions Small population approach in replicating significant SNPs is useful in complex phenotypes like suicide. This study explored the region-specific demographics of India by identifying vulnerable population for suicide via genetic association analysis in bringing into academic and administrative forum, the importance of suicide as a disease and its biological basis.

中文翻译：

---

重新测试报告了印度东北部历史高风险孤立人群中与自杀相关的重要 SNP

背景 家庭和双胞胎研究支持自杀的遗传素质。已知的候选基因途径很少，但并不能完全解释自杀遗传风险的复杂性。最近选择全基因组关联研究 (GWAS) 的调查发现了其他目标，但复制仍然是一个挑战。在这方面，发现几种复杂疾病表型中的小孤立群体方法令人鼓舞。本研究试图在印度东北部的一个小型历史高风险孤立人群中重新测试一些报告的重要 SNP 自杀。方法本研究考虑了210例（包括抑郁症、自杀未遂者和抑郁症+自杀未遂者）和249名对照者，并对其精神参数进行了评估。在各种遗传模型下使用关联方法重新测试了 16 个报告的自杀行为的重要 SNP。GeneMANIA 工具的网络用于相关基因的功能预测。结果 7 个 SNP（6 个基因）在不同的遗传模型中仍然显着。在具有重要 SNP 的网络基因上，发现 IL7、RHEB、CTNN3、KCNIP4、ARFGEF3 与已知的候选基因通路相互作用，而 SNP rs1109089 (RHEB) 获得了早期表达研究的进一步支持。NUGGC基因是完全隔离的。结论 复制重要 SNP 的小群体方法在复杂表型（如自杀）中很有用。