Abstract
The association of the tumor necrosis factor alpha (TNFΞ±) βG308A promoter polymorphism with schizophrenia has complemented clinical findings of increased levels of the TNFΞ± 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 TNFΞ± gene is located as well as association with the βG308A promoter polymorphism. While the common Gβallele shows association in our sample, association with the Aβallele 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 165βkb region around this polymorphism. We detected nominally significant associations (Pβ<β0.05) of three markers (including the βG308A promoter polymorphism) and multiple haplotypes with schizophrenia in our sample of 204 families (79 sibβpairs 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. Β© 2006 WileyβLiss, Inc.