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

Sudesh, Ravi, Thalamuthu, Anbupalam, John, Sujit, Thara, Rangaswamy, Mowry, Bryan and Munirajan, Arasamabattu Kannan (2018) 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 research, . doi:10.1016/j.schres.2018.03.028


Author Sudesh, Ravi
Thalamuthu, Anbupalam
John, Sujit
Thara, Rangaswamy
Mowry, Bryan
Munirajan, Arasamabattu Kannan
Title Replication of GWAS identified miR-137 and its target gene polymorphisms in Schizophrenia of South Indian population and meta-analysis with Psychiatric Genomics Consortium
Journal name Schizophrenia research   Check publisher's open access policy
ISSN 1573-2509
Publication date 2018-03-26
Sub-type Article (original research)
DOI 10.1016/j.schres.2018.03.028
Open Access Status Not yet assessed
Abstract 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.
Keyword CACNA1C
Meta-analysis
PRS
Replication of GWAS
Schizophrenia
mir137 and its target
rs4765905
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Pubmed Import
 
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Created: Wed, 04 Apr 2018, 10:04:38 EST