Replication of GWAS identified miR-137 and its target gene polymorphisms in Schizophrenia of South Indian population and meta-analysis with Psychiatric Genomics Consortium

Schizophrenia is a complex psychiatric disorder involving multiple genes each contributing a small risk. Genome-wide association studies (GWASs) have identified hundreds of risk loci for schizophrenia including miR-137, a miRNA shown to be involved in neuronal development. Several genes regulated by miR-137 were also reported as top risk genes associated with schizophrenia and has been hypothesised that the dysregulation of miR-137 and its target could be involved in the aetiology of schizophrenia. Here, we replicated the four European GWAS hits, miR-137-rs1625579 and three of its validated target gene loci SNPs (ZNF804a-rs1344706, CACNA1C-rs4765905 and TCF4-rs9960767) by genotyping in 2074 samples (schizophrenia cases-1005; controls-1069) from South Indian Population. In this study, only the CACNA1C rs4765905 showed a significant association (OR=1.24, p=0.006). Three SNPs (rs1625579, rs1344706 and rs4765905) showed a consistent direction of effect with previous studies and the polygenic risk score constructed using the weighted sum of these three SNPs showed a significant association with Schizophrenia in this population (OR=3.78, p=0.005). Further, we carried out meta-analysis combining our results with the Psychiatric Genomics Consortium (PGC2) data and observed a considerable increase in GWAS significance.