BACKGROUND: ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients. METHODS: 69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2×2 analysis of variance. RESULTS: 1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers. 2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group. LIMITATION: The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated. CONCLUSIONS: The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia.
BACKGROUND:ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenicpatients. METHODS: 69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophreniapatients and healthy controls was analyzed using a full-factorial 2×2 analysis of variance. RESULTS: 1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophreniapatients and lower WM density in healthy controls in comparison with the non-risk allele carriers. 2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group. LIMITATION: The influence of antipsychotics to the white matter in schizophrenicpatients was not fully eliminated. CONCLUSIONS: The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia.
Authors: T Ikuta; B D Peters; S Guha; M John; K H Karlsgodt; T Lencz; P R Szeszko; A K Malhotra Journal: Schizophr Res Date: 2014-03-27 Impact factor: 4.939
Authors: H Cousijn; M Rijpkema; A Harteveld; P J Harrison; G Fernández; B Franke; A Arias-Vásquez Journal: Mol Psychiatry Date: 2012-01-24 Impact factor: 15.992