title: A comprehensive genetic association and functional study of TNF in schizophrenia risk.
abstract: In view of prior reports suggesting associations between polymorphisms of the tumor necrosis factor gene (TNF) and schizophrenia, we sequenced all exons, introns and 7 kb flanking sequence at TNF in DNA pooled from 125 Caucasian schizophrenia cases and 200 controls. We identified 18 SNPs of which we selected and genotyped 8 among 244 cases and 276 controls. We detected no significant genotype or haplotype associations in the entire sample or in subgroups defined by gender or exposure to HSV1, HSV2, CMV, or Toxoplasma gondii. We used a dual-luciferase expression assay to quantify TNF expression driven by each common promoter haplotype in a neuroblastoma cell line. Three haplotypes drove significantly lower levels of TNF expression than the most common haplotype, including a haplotype with -308A, the allele reported to increase risk for schizophrenia (in contrast to earlier reports). We find no evidence to implicate TNF gene polymorphisms for schizophrenia risk in our sample.
authors.affiliation: Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, Pennsylvania 15213, USA.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Shirts
authors.forename: Mikhil
authors.initials: M
authors.lastname: Bamne
authors.forename: Jung Jin
authors.initials: JJ
authors.lastname: Kim
authors.forename: Michael
authors.initials: M
authors.lastname: Talkowski
authors.forename: Joel
authors.initials: J
authors.lastname: Wood
authors.forename: Robert
authors.initials: R
authors.lastname: Yolken
authors.forename: Vishwajit L
authors.initials: VL
authors.lastname: Nimgaonkar
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D012559:Schizophrenia / Q000208:ethnology / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics
chemical_list: C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha