Re-testing reported significant SNPs related to suicide in a historical high -risk isolated population from north east India

Abstract

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.