Journal Article

Evaluation of HLA Polymorphisms in Relation to Schizophrenia Risk and Infectious Exposure

Mikhil Bamne, Joel Wood, Kodavali Chowdari, Annie M. Watson, Cemil Celik, Hader Mansour, Lambertus Klei, Ruben C. Gur, L. DiAnne Bradford, Monica E. Calkins, Alberto B. Santos, Neil Edwards, Joseph Kwentus, Joseph P. McEvoy, Trina B. Allen, Robert M. Savage, Henry A. Nasrallah, Raquel E. Gur, Rodney T. Perry, Rodney C.P. Go, Bernie Devlin, Robert Yolken and Vishwajit L. Nimgaonkar

in Schizophrenia Bulletin

Published on behalf of Maryland Psychiatric Research Center

Volume 38, issue 6, pages 1149-1154
Published in print November 2012 | ISSN: 0586-7614
Published online September 2012 | e-ISSN: 1745-1701 | DOI: https://dx.doi.org/10.1093/schbul/sbs087
Evaluation of HLA Polymorphisms in Relation to Schizophrenia Risk and Infectious Exposure

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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.

Keywords: HLA; gene; HSV-1; cytomegalovirus; schizophrenia; African American; kwd>

Journal Article.  3165 words.  Illustrated.

Subjects: Child and Adolescent Psychiatry

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