Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, PA, USA.
Schizophr Bull. 2012 Nov;38(6):1149-54. doi: 10.1093/schbul/sbs087. Epub 2012 Sep 10.
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.
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.
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.
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.
全基因组关联研究（GWAS）表明，6p21.3-22.1 染色体上的单核苷酸多态性（SNPs）和人类白细胞抗原（HLA）区域是精神分裂症（SZ）的常见危险因素。其他研究表明，病毒和原生动物暴露也与 SZ 有关。我们的研究检测了染色体 6pSNP 对 SZ 风险的影响，包括有无暴露。
对 604 例非裔美国 SZ 患者（病例组）和 404 例对照（对照组）进行了 GWAS 显著 SNP 和与祖先相关的标记 SNP 分析。采用特定抗体检测法检测单纯疱疹病毒 1 型（HSV-1）、巨细胞病毒（CMV）和刚地弓形虫（TOX）的暴露情况。
对人群混合进行校正后，有 5 个 SNP 与 SZ 呈显著相关（P<0.05，未经多重比较校正）。接下来，对这些 SNP 与传染性暴露的关系进行了分析。多变量分析表明，rs3130297 基因型与 HSV-1 暴露之间存在显著关联，相关等位基因与 SZ 风险等位基因不同。
我们提出了一个 SZ 发病模型，该模型将 HLA 区域的基因组变异和神经嗜性病毒暴露结合起来，以在额外的、独立的非裔美国样本中进行测试。
