A comprehensive genetic association and functional study of TNF in schizophrenia risk

Brian H. Shirts, Mikhil Bamne, Jung Jin Kim, Michael Talkowski, Joel Wood, Robert Yolken, Vishwajit L. Nimgaonkar

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)7-13
Number of pages7
JournalSchizophrenia Research
Volume83
Issue number1
DOIs
StatePublished - Mar 2006

Keywords

  • Association
  • Expression
  • Promoter
  • Schizophrenia
  • TNF

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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