Genome-wide supported psychosis risk variant in ZNF804A gene and impact on cortico-limbic WM integrity in schizophrenia

Kuswanto, Carissa Nadia, Woon, Puay-San, Zheng, Xue Bin, Qiu, Anqi, Sitoh, Yih-Yian, Chan, Yiong Huak, Liu, Jianjun, Williams, Hywel ORCID: https://orcid.org/0000-0001-7758-0312, Ong, Wei Yi and Sim, Kang 2012. Genome-wide supported psychosis risk variant in ZNF804A gene and impact on cortico-limbic WM integrity in schizophrenia. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 159B (3) , pp. 255-262. 10.1002/ajmg.b.32032

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Abstract

Genome-wide association, case association genetic and metaanalytic studies have highlighted ZNF804A as a robust genomewide 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 brainWM(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 ¼9.36, P¼0.003) and diagnosis–genotype interactions (left parietal lobe: Adjusted F1,147 ¼7.39, P¼0.007; right parietal lobe: Adjusted F1,147 ¼ 6.95, P¼0.009; right medial temporal lobe: Adjusted F1,147 ¼8.79, P¼0.004; left cingulate gyrus: Adjusted F1,147 ¼8.02, P¼0.005). 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 influenceWMintegrity 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	WM; schizophrenia; cortico-limbic; fractional anisotropy; ZNF804A
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Last Modified:	21 Oct 2022 10:25
URI:	https://orca.cardiff.ac.uk/id/eprint/40114

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