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

Schizophr Res. 2015 Mar;162(1-3):112-7. doi: 10.1016/j.schres.2014.12.031. Epub 2015 Jan 9.

Abstract

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.

Keywords: Meta-analysis; PGC; Schizophrenia; TDT; rs1062613; rs548181.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / genetics
  • Case-Control Studies
  • Family
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotyping Techniques
  • Humans
  • India
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Receptor, ErbB-4 / genetics
  • Receptors, Serotonin, 5-HT3 / genetics
  • Schizophrenia / genetics*
  • Trans-Activators / genetics
  • White People / genetics

Substances

  • EBF1 protein, human
  • HTR3A protein, human
  • Receptors, Serotonin, 5-HT3
  • Trans-Activators
  • ERBB4 protein, human
  • Receptor, ErbB-4