How to Cite this Article: Kuswanto CN, Woon P-S, Zheng XB, Qiu A, Sitoh Y-Y, Chan YH, Liu J, Williams H, Ong WY, Sim K. 2012. Genome-Wide Supported Psychosis Risk Variant in ZNF804A Gene and Impact on Cortico–Limbic WM Integrity in Schizophrenia. Am J Med Genet Part B 159B:255–262.
Genome-wide supported psychosis risk variant in ZNF804A gene and impact on cortico–limbic WM integrity in schizophrenia†
Article first published online: 10 FEB 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 159B, Issue 3, pages 255–262, April 2012
How to Cite
Kuswanto, C. N., Woon, P.-S., Zheng, X. B., Qiu, A., Sitoh, Y.-Y., Chan, Y. H., Liu, J., Williams, H., Ong, W. Y. and Sim, K. (2012), Genome-wide supported psychosis risk variant in ZNF804A gene and impact on cortico–limbic WM integrity in schizophrenia. Am. J. Med. Genet., 159B: 255–262. doi: 10.1002/ajmg.b.32032
- Issue published online: 7 MAR 2012
- Article first published online: 10 FEB 2012
- Manuscript Accepted: 19 JAN 2012
- Manuscript Received: 26 AUG 2011
- National Healthcare Group, Singapore. Grant Number: SIG/05004, SIG/05028
- Singapore Bioimaging Consortium. Grant Number: RP C-009/2006
- A*STAR SERC. Grant Number: 082-101-0025
- fractional anisotropy;
Genome-wide association, case association genetic and meta-analytic studies have highlighted ZNF804A as a robust genome-wide supported susceptibility gene for schizophrenia (SCZ). In view of the possible involvement of ZNF804A gene in early neurodevelopment and cellular processes including oligodendrocyte proliferation and differentiation, we examined the effect of ZNF804A on brain WM (WM) integrity in patients with SCZ. Based on extant data in healthy controls (HC), we hypothesized that ZNF804A risk variant rs1344706 is associated with lower fractional anisotropy (FA) in brain regions within cortico-limbic circuits, namely frontal, parietal, medial temporal lobes, and cingulate gyri in SCZ. A total of 200 Chinese participants (125 patients with DSM-IV diagnosis of SCZ and 75 controls) were genotyped using blood samples, a subset of 153 participants (89 patients with DSM-IV diagnosis of SCZ and 64 controls) underwent structural magnetic resonance imaging and diffusion tensor imaging (DTI). There are significant effects of diagnosis (left cingulate gyrus: Adjusted F1,149 = 9.36, P = 0.003) and diagnosis–genotype interactions (left parietal lobe: Adjusted F1,147 = 7.39, P = 0.007; right parietal lobe: Adjusted F1,147 = 6.95, P = 0.009; right medial temporal lobe: Adjusted F1,147 = 8.79, P = 0.004; left cingulate gyrus: Adjusted F1,147 = 8.02, P = 0.005). Specifically, we found that patients with SCZ who are risk T homozygotes have lower FA in bilateral parietal lobes, and left cingulate gyrus compared with G carriers. Compared with risk T homozygotes in HC, patients with SCZ who are risk T homozygotes have decreased FA in bilateral parietal lobes, and left cingulate gyrus as well as right medial temporal lobe. Our findings suggest that ZNF804A risk variant influence WM integrity involving cortico-limbic brain regions in SCZ and highlight the importance of investigating the impact of genome-wide supported risk factors on intermediate phenotypes with potential to shed light on the neurobiology of SCZ. © 2012 Wiley Periodicals, Inc.