Evaluation of HLA polymorphisms in relation to schizophrenia risk and infectious exposure.

Published

Journal Article

BACKGROUND: Genome-wide association studies (GWAS) implicate single nucleotide polymorphisms (SNPs) on chromosome 6p21.3-22.1, the human leukocyte antigen (HLA) region, as common risk factors for schizophrenia (SZ). Other studies implicate viral and protozoan exposure. Our study tests chromosome 6p SNPs for effects on SZ risk with and without exposure. METHOD: GWAS-significant SNPs and ancestry-informative marker SNPs were analyzed among African American patients with SZ (n = 604) and controls (n = 404). Exposure to herpes simplex virus, type 1 (HSV-1), cytomegalovirus (CMV), and Toxoplasma gondii (TOX) was assayed using specific antibody assays. RESULTS: Five SNPs were nominally associated with SZ, adjusted for population admixture (P < .05, uncorrected for multiple comparisons). These SNPs were next analyzed in relation to infectious exposure. Multivariate analysis indicated significant association between rs3130297 genotype and HSV-1 exposure; the associated allele was different from the SZ risk allele. CONCLUSIONS: We propose a model for the genesis of SZ incorporating genomic variation in the HLA region and neurotropic viral exposure for testing in additional, independent African American samples.

Full Text

Duke Authors

Cited Authors

  • Bamne, M; Wood, J; Chowdari, K; Watson, AM; Celik, C; Mansour, H; Klei, L; Gur, RC; Bradford, LD; Calkins, ME; Santos, AB; Edwards, N; Kwentus, J; McEvoy, JP; Allen, TB; Savage, RM; Nasrallah, HA; Gur, RE; Perry, RT; Go, RCP; Devlin, B; Yolken, R; Nimgaonkar, VL

Published Date

  • November 2012

Published In

Volume / Issue

  • 38 / 6

Start / End Page

  • 1149 - 1154

PubMed ID

  • 22966150

Pubmed Central ID

  • 22966150

Electronic International Standard Serial Number (EISSN)

  • 1745-1701

Digital Object Identifier (DOI)

  • 10.1093/schbul/sbs087

Language

  • eng

Conference Location

  • United States