Polymorphisms in MICB are associated with human herpes virus seropositivity and schizophrenia risk

Viral infection may be a risk factor for schizophrenia and has been associated with decreased cognitive functioning in patients. We report associations of SNPs at MICB (MHC class I polypeptide-related sequence B, chromosome 6p21) with cytomegalovirus and herpes simplex virus 1 seropositivity. We previously found associations with schizophrenia on chromosome 6p21 among patients seropositive for cytomegalovirus (CMV) and herpes simplex virus 1 (HSV1). To localize the associations further, we genotyped 26 SNPs spanning 100 kb in a sample of 236 Caucasian schizophrenia patients and 240 controls. Based on suggestive associations, we selected five SNPs at MICB to assay among two additional Caucasian samples that had been serotyped for CMV and HSV1: a case-control sample recruited in Baltimore (n = 272 cases, 108 controls), and a case-parent trio sample recruited in Pittsburgh (n = 221). Among Baltimore control individuals there were significant associations with antibody status for infectious agents: rs1051788 with HSV1 seropositivity (p = 0.006) and rs2523651 with cytomegalovirus seropositivity (p = 0.001). The former association was also detectable among the parents of cases recruited in Pittsburgh (p = 0.024). Neither viral association was noted among the schizophrenia cases. With respect to schizophrenia risk, significant transmission distortion was noted at rs1051788 and rs1055569 among the case-parent trios regardless of antibody status (p = 0.014 and 0.036 respectively). A similar trend for association with schizophrenia liability at rs1051788 in the Baltimore sample did not attain statistical significance. There are a number of explanations for the associations, including chance variation, as well as gene-virus interactions. Further replicate studies are warranted, as are functional studies of these polymorphisms.