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Evaluation of association of SNPs in the TNF alpha gene region with schizophrenia
Author(s) -
Morar B.,
Schwab S.G.,
Albus M.,
Maier W.,
Lerer B.,
Wildenauer D.B.
Publication year - 2006
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30451
Subject(s) - linkage disequilibrium , haplotype , single nucleotide polymorphism , genetics , allele , genetic association , major histocompatibility complex , biology , gene , promoter , genotype , gene expression
The association of the tumor necrosis factor alpha (TNFα) −G308A promoter polymorphism with schizophrenia has complemented clinical findings of increased levels of the TNFα cytokine in schizophrenic patients, with some support for a functional consequence of the variant. Our previous studies of genetic causes in schizophrenia supported findings of linkage to the major histocompatibility complex (MHC) region where the TNFα gene is located as well as association with the −G308A promoter polymorphism. While the common G‐allele shows association in our sample, association with the A‐allele has been reported by other groups. This suggests linkage disequilibrium (LD) rather than direct involvement in the disorder. In order to define LD of DNA variants with the disorder in this area, we analyzed 36 SNPs in a 165‐kb region around this polymorphism. We detected nominally significant associations ( P < 0.05) of three markers (including the −G308A promoter polymorphism) and multiple haplotypes with schizophrenia in our sample of 204 families (79 sib‐pairs and 125 trios). The association is largely restricted to a 30 kb high LD region/block and should assist in the identification of a schizophrenia susceptibility gene within the block or elsewhere in the MHC. © 2006 Wiley‐Liss, Inc.