Evidence for schizophrenia susceptibility alleles in the Indian population: An association of neurodevelopmental genes in case-control and familial samples

Schizophrenia is a severe psychiatric disorder with lifetime prevalence of ~ 1% worldwide. A genotyping study was conducted using a custom panel of Illumina 1536 SNPs in 840 schizophrenia cases and 876 controls (351 patients and 385 controls from North India; and 436 patients, 401 controls and 143 familial samples with 53 probands containing 37 complete and 16 incomplete trios from South India). Meta-analysis of this population of Indo-European and Dravidian ancestry identified three strongly associated variants with schizophrenia: STT3A (rs548181, p = 1.47 × 10− 5), NRG1 (rs17603876, p = 8.66 × 10− 5) and GRM7 (rs3864075, p = 4.06 × 10− 3). Finally, a meta-analysis was conducted comparing our data with data from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ) that supported rs548181 (p = 1.39 × 10− 7). In addition, combined analysis of sporadic case-control association and a transmission disequilibrium test in familial samples from South Indian population identified three associations: rs1062613 (p = 3.12 × 10− 3), a functional promoter variant of HTR3A; rs6710782 (p = 3.50 × 10− 3), an intronic variant of ERBB4; and rs891903 (p = 1.05 × 10− 2), an intronic variant of EBF1. The results support the risk variants observed in the earlier published work and suggest a potential role of neurodevelopmental genes in the schizophrenia pathogenesis.