| 1 | Psychiatry Res 2010 Jul 178: 266-9 |
|---|---|
| PMID | 20471694 |
| Title | Association of histone deacetylase genes with schizophrenia in Korean population. |
| Abstract | Histone deacetylases (HDACs) are pivotal enzymes in the epigenetic modification or regulatory mechanisms of gene transcription. Based on previous assertions that the pathophysiology of schizophrenia is associated with epigenetics, we hypothesized that polymorphisms of HDAC genes might be related to schizophrenia. We recruited 278 patients with schizophrenia and 234 normal controls from a Korean population. Clinical information of the group with schizophrenia was obtained from medical records, the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), and the Operational Criteria Checklist (OPCRIT). Three single-nucleotide polymorphisms (SNPs) in HDAC genes were selected, including rs2530223 of HDAC3, rs1063639 of HDAC4, and rs1555048 of HDAC10. For the analysis of genetic data, SNPStats, SNPAnalyzer, and Helixtree programs were used. In the present study, rs1063639 of the HDAC4 gene showed associations with schizophrenia in the codominant and dominant models. In the analysis of clinical phenotypes, smoking status was associated with rs2530223 of HDAC3 in the codominant and recessive models. The results suggest that HDAC3 and HDAC4 genes might play a role in the pathophysiology of schizophrenia in a Korean population. |
| SCZ Keywords | schizophrenia |
| 2 | Schizophr. Res. 2014 Dec 160: 97-103 |
| PMID | 25445625 |
| Title | Family-based association study of common variants, rare mutation study and epistatic interaction detection in HDAC genes in schizophrenia. |
| Abstract | Histone deacetylases (HDACs) are key enzymes of histone acetylation, and abnormalities in histone modifications and in the level of HDAC proteins have been reported in schizophrenia. The objective of the present study was to systematically test the HDAC genes for its association with schizophrenia. A family-based genetic association study (951 Caucasian subjects in 313 nuclear families) using 601 tag-single nucleotide polymorphisms in HDAC genes was conducted followed by a replication study of top-ranked markers in a sample of 1427 Caucasian subjects from 241 multiplex families and 176 trios. Epistasis interaction was tested by using the pedigree-based generalized multifactor dimensionality reduction (GMDR). Furthermore, we analyzed exome sequencing data of 1134 subjects for detection of rare mutations in HDAC genomic regions. In the exploratory study, ten markers were in significant association with schizophrenia (P<0.01). One maker rs14251 (HDAC3) was replicated (P=0.04) and remained significant in the whole sample (P=0.004). GMDR identified that a significant three-locus interaction model was detected involving rs17265596 (HDAC9), rs7290710 (HDAC10) and rs7634112 (HDAC11) with a good testing accuracy (0.58). No rare mutations were found associated with schizophrenia. This first exploratory systematic study of the HDAC genes provides consistent support for the involvement of the HDAC3 gene in the etiology of schizophrenia. A statistical epistatic interaction between HDAC9, HDAC10, and HDAC11 was detected and seems biologically plausible. |
| SCZ Keywords | schizophrenia |