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

Abstract:

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.

journal_name

Schizophr Bull

journal_title

Schizophrenia bulletin

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 RC,Devlin B,Yolken R,Nimgao

doi

10.1093/schbul/sbs087

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

1149-54

issue

6

eissn

0586-7614

issn

1745-1701

pii

sbs087

journal_volume

38

pub_type

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