Association of tumor necrosis factor alpha gene -G308A polymorphism with schizophrenia

Sibylle G. Schwab, Stephanie Mondabon, Michael Knapp, Margot Albus, Joachim Hallmayer, Margitta Borrmann-Hassenbach, Matyas Trixler, Magdalena Groß, Thomas G. Schulze, Marcella Rietschel, Bernard Lerer, Wolfgang Maier, Dieter B. Wildenauer

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41 Scopus citations


Background: Tumor necrosis factor alpha (TNFα), a cytokine involved in inflammatory processes, has been implicated in the pathophysiology of schizophrenia. The chromosomal location in the major histocompatibility complex (MHC) region on 6p21.1-21.3, a region with evidence for linkage, suggests a role in susceptibility to schizophrenia. Association of the minor (A) allele of the -G308A TNFα gene polymorphism with schizophrenia has been reported [Mol. Psychiatry 6 (2001) 79]. Methods: Association of the -G308A TNFα gene and the lymphotoxin alpha (LTα)+A252G gene polymorphisms with schizophrenia was studied in 79 sib pair families with linkage in the MHC region and in 128 trio families using the transmission disequilibrium test (TDT). Results: Weak association of the common G allele was detected for TNFα -G308A in both samples independently with borderline significance in the sib pair families (0.064) and with a nominally significant value of P=0.022 in the trio families. Combining both samples produced P=0.003, while LTα+A252G, located approximately 2-3 kb distally, revealed P=0.03 and the two locus haplotype yielded a P value of 0.001. Conclusion: Our data suggests association of the common G allele of the -G308A TNFα gene polymorphism with schizophrenia in a sample of 207 families. However, linkage disequilibrium with a different allele of the TNFα gene or another gene in the MHC region cannot be excluded.

Original languageEnglish (US)
Pages (from-to)19-25
Number of pages7
JournalSchizophrenia Research
Issue number1
StatePublished - Dec 1 2003
Externally publishedYes


  • Association
  • Cytokines
  • Linkage disequilibrium
  • LTα
  • Schizophrenia
  • TNFα

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Behavioral Neuroscience
  • Biological Psychiatry
  • Neurology
  • Psychology(all)


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