Replication of association between schizophrenia and ZNF804A in the Irish Case-Control Study of Schizophrenia sample.
paper
Cited
Public
- Authors
- Riley, B; Thiselton, D; Maher, B S; Bigdeli, T; Wormley, B; McMichael, G O; Fanous, A H; Vladimirov, V; O'Neill, F A; Walsh, D; Kendler, K S
- Year
- 2010
- Journal
- Molecular psychiatry
- PMID
- 19844207
- DOI
- 10.1038/mp.2009.109
- PMCID
- PMC2797562
A recent genome-wide association study reported association between schizophrenia and the ZNF804A gene on chromosome 2q32.1. We attempted to replicate these findings in our Irish Case-Control Study of Schizophrenia (ICCSS) sample (N=1021 cases, 626 controls). Following consultation with the original investigators, we genotyped three of the most promising single-nucleotide polymorphisms (SNPs) from the Cardiff study. We replicate association with rs1344706 (trend test one-tailed P=0.0113 with the previously associated A allele) in ZNF804A. We detect no evidence of association with rs6490121 in NOS1 (one-tailed P=0.21), and only a trend with rs9922369 in RGRIP1L (one-tailed P=0.0515). On the basis of these results, we completed genotyping of 11 additional linkage disequilibrium-tagging SNPs in ZNF804A. Of 12 SNPs genotyped, 11 pass quality control criteria and 4 are nominally associated, with our most significant evidence of association at rs7597593 (P=0.0013) followed by rs1344706. We observe no evidence of differential association in ZNF804A on the basis of family history or sex of case. The associated SNP rs1344706 lies in approximately 30 bp of conserved mammalian sequence, and the associated A allele is predicted to maintain binding sites for the brain-expressed transcription factors MYT1l and POU3F1/OCT-6. In controls, expression is significantly increased from the A allele of rs1344706 compared with the C allele. Expression is increased in schizophrenic cases compared with controls, but this difference does not achieve statistical significance. This study replicates the original reported association of ZNF804A with schizophrenia and suggests that there is a consistent link between the A allele of rs1344706, increased expression of ZNF804A and risk for schizophrenia.
ZNF804A gene expression in the SMRI sample. A. Comparison of ZNF804A expression in schizophrenic (SCH) and control (CON) samples.B. ZNF804A expression in SMRI control samples stratified by rs1344706 allele.
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| Name | Type |
|---|---|
| age-related macular degeneration | phenotype |
| All cases local | cohort |
| Ambion miRvana kit local | drug |
| Anglo-Celtic discovery sample local | cohort |
| Anglo-Celtic population local | cohort |
| Army reserve local | cohort |
| brain | anatomy |
| Cardiff study local | cohort |
| cases | cohort |
| case samples | cohort |
| CATIE local | cohort |
| CON | phenotype |
| control | cohort |
| controls | cohort |
| cortex | anatomy |
| Crohnβs disease | phenotype |
| CSF2RA | gene |
| cytokines | drug |
| dorsolateral prefrontal cortex | anatomy |
| episodic memory | phenotype |
| European-descended samples local | cohort |
| expression differences local | phenotype |
| family history negative | phenotype |
| family history of alcoholism | phenotype |
| FH+ | drug |
| FH+ cases local | cohort |
| FHβ cases local | cohort |
| FHN | cohort |
| full sample | cohort |
| HapMap | cohort |
| higher expression local | phenotype |
| hippocampus | anatomy |
| Hmx2 local | gene |
| Homez local | gene |
| HPRT1 | gene |
| Iberian peninsula | cohort |
| ICCSS | cohort |
| IL3R local | gene |
| Ireland | cohort |
| Ireland and Northern Ireland population local | cohort |
| Irish case/control sample local | cohort |
| Irish national police local | cohort |
| Irish population local | cohort |
| Irish samples local | cohort |
| mtDNA local | variant |
| MYT1 | gene |
| Myt1l | gene |
| Northern Ireland local | cohort |
| Northern Ireland Blood Transfusion Service donors local | cohort |
| Nos1 | gene |
| obesity | phenotype |
| Pou3f1 | gene |
| prefrontal cortex | anatomy |
| prostate cancer | phenotype |
| psychosis | phenotype |
| RGRIP1L local | gene |
| Roscommon Family Study local | cohort |
| rs13393273 local | variant |
| rs1344706 | variant |
| rs1480481 local | variant |
| rs17508595 local | variant |
| rs3931790 local | variant |
| rs4129148 | variant |
| rs4667001 local | variant |
| rs6490121 local | variant |
| rs7597593 local | variant |
| rs7597593_T_TTAA haplotype local | variant |
| rs7603001 local | variant |
| rs7605689 local | variant |
| rs9922369 local | variant |
| schizoaffective disorder | phenotype |
| schizophrenia | phenotype |
| schizophrenic case cohort local | cohort |
| sex | phenotype |
| SMRI local | cohort |
| SMRI CON local | cohort |
| SMRI postmortem CON samples local | cohort |
| south western France local | cohort |
| Stanley Medical Research Institute local | cohort |
| study cohort | cohort |
| TBP | gene |
| TTAA haplotype local | variant |
| type 1 diabetes | phenotype |
| type 2 diabetes | phenotype |
| United Kingdom | cohort |
| unspecified functional psychosis | phenotype |
| Wales | cohort |
| Wellcome Trust Case/Control Consortium local | cohort |
| Y chromosome local | variant |
| ZNF804A | gene |
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