We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611–rs10043986, r2 = 0.008; rs10043986–rs4704591, r2 = 0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case–control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR) = 1.11, 95% confidence interval (CI) = 1.04–1.18, P = 8.2 × 10−4 and rs4704591, OR = 1.07, 95% CI = 1.03–1.11, P = 3.0 × 10−4). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR = 1.11, 95% CI = 1.03–1.17, P = 0.0026 and rs4704591, OR = 1.07, 95% CI = 1.02–1.11, P = 0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted.

Little is known about hepatic T lymphocyte subpopulations in the human liver. The aim of this study was to document the various subpopulations present in the liver and compare them to peripheral T lymphocytes in the same patients. Normal hepatic tissue was obained at time of transplant from five patients, and a single cell suspension of lymphocytes were prepared by standard methods. Ceils were stained with monoclonal antibodies specific for CD8ct and CD8B chains, CD4, CD8, CD3, o~BTCR, and ySTCR, and analyzed by two and three colour flow cytometry. Of the hepatic CD3+ cells, 71% were CD8+ and 25% were CD4+, with a CD4/CD8 ratio of 1:3 in contrast to the peripheral CD4/CD8 ratio of 2:1.18% of the hepatic CD3+ cells expressed ySTCR. Significantly, CD8~ct accounted for 27% [mean] of the total hepatic CD8+ population. Conclusion: There is now evidence that the adult human gut can support extrathymic T cell differentation. A significant population of hepatic CD8txct cells would suggest that the liver is also a site of extrathymic differentiation, which may have important implications for the understanding of autoimmunity and graft tolerance.

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