LAUSR

Background Schizophrenia is a polygenic neuropsychiatric disorder wherein specific molecular or phenotypic markers have not been reported, with several promising findings but inconsistent replication. Nevertheless, different markers from chromosome 6, discussed repeatedly and reinforced by GWAS findings, remain the most promising leads. The present study was carried out to replicate the important GWAS findings (p Methods Schizophrenia cases (n=1035) and matched healthy controls (n=1035) were recruited at PGIMER-Dr.R.M.L. hospital. Controls included age and gender matched psychiatrically healthy adults and cord blood samples. Using Sequenome platform, 26 markers were evaluated. In a subset of the samples (n=173 cases; n=87 controls), 8 different cognitive domains were evaluated using the UPenn Computerized Neuropsychological Battery, for the markers. Results Three markers namely rs2064430 (p=0.04, OR= 1.14, CI=1.01-1.3, AHI), rs6932590 (p=0.05, OR= 0.85, CI=0.73-1.00, intergenic), rs6916921 (p=0.05,OR=1.19, CI=1.00-1.43, NFKBIL1) showed modest association to DSM IV schizophrenia diagnosis under allelic test of association while rs3130615 and rs6916394 showed genotypic (p=0.04, p=0.02) and recessive association (p=0.01, 0.05) but none withstood Bonferroni correction. The most significant 2 marker haplotype using PLINK sliding window came from four regions: 1) intergenic region -rs6932590|rs3800318 (TA, p=0.02) 2) HLADQA1 region- rs377763|rs9273012 (GA, p=0.04) and 3) TNF region- rs1800610|rs986475 (CC, p=0.03) 4) MICB region- rs3130615| rs2516489 (CG, p=0.04). Significant association was observed among cases for rs377763 (p = 1.54*10-6) with ‘Sensorimotor functioning’ domain of the battery. Discussion The present study, although reaffirms association of a few chromosome 6 markers to schizophrenia in this ethnically distinct North Indian population; was of far lower magnitude than p=10-8 seen in initial GWAS findings.