UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Rare variant analysis in multiply affected families, association studies and functional analysis suggest a role for the ITGΒ4 gene in schizophrenia and bipolar disorder

O'Brien, NL; Fiorentino, A; Curtis, D; Rayner, C; Petrosellini, C; Al Eissa, M; Bass, NJ; ... Sharp, SI; + view all (2018) Rare variant analysis in multiply affected families, association studies and functional analysis suggest a role for the ITGΒ4 gene in schizophrenia and bipolar disorder. Schizophrenia Research , 199 pp. 181-188. 10.1016/j.schres.2018.03.001. Green open access

[thumbnail of PIIS092099641830149X.pdf]
Preview
Text
PIIS092099641830149X.pdf - Published Version

Download (619kB) | Preview

Abstract

Recent results imply that rare variants contribute to the risk of schizophrenia. Exome sequence data from the UK10K project was used to identify three rare, amino acid changing variants in the ITGB4 gene which segregated with schizophrenia in two families: rs750367954, rs147480547 and rs145976111. Association analysis was carried out in the exome-sequenced Swedish schizophrenia study and in UCL schizophrenia and bipolar cases and controls genotyped for these variants. A gene-wise weighted burden test was performed on a trio sample of schizophrenia cases and their parents. rs750367954 was seen in two Swedish cases and in no controls. The other two variants were commoner in cases than controls in both Swedish and UCL cohort samples and an overall burden test was significant at p=0.0000031. The variants were not observed in the trio sample but ITGB4 was most highly ranked out of 14,960 autosomal genes in a gene-wise weighted burden test. The effect of rs147480547 and rs145976111 was studied in human neuroblastoma SH-SY5Y cells. Cells transfected with both variants had increased proliferation at both 24 and 48h (p=0.013 and p=0.05 respectively) compared to those with wild-type ITGB4. Taken together, these results suggest that rare variants in ITGB4 which affect function may contribute to the aetiology of schizophrenia and bipolar disorder.

Type: Article
Title: Rare variant analysis in multiply affected families, association studies and functional analysis suggest a role for the ITGΒ4 gene in schizophrenia and bipolar disorder
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.schres.2018.03.001
Publisher version: https://doi.org/10.1016/j.schres.2018.03.001
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Genetic risk, Genotyping, Psychosis, Sequencing
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10045940
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item