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Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder

Bipolar disorder (BD) is a complex psychiatric disorder with strong heritability. Identification of new BD risk genes will help determine the mechanism underlying disease pathogenesis. In the present study, we carried out whole genome sequencing for a Chinese BD family with three affected members an...

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Autores principales: Liu, Fa-rong, Zhou, Yunqiang, Wang, Yong, Huang, Ling-ling, Zhang, Xian, Luo, Hong, Wu, Su-ying, Lyu, Hai-yan, Huang, Li-huan, Xu, Huaxi, Zhang, Yun-wu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482626/
https://www.ncbi.nlm.nih.gov/pubmed/36115840
http://dx.doi.org/10.1038/s41398-022-02163-x
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author Liu, Fa-rong
Zhou, Yunqiang
Wang, Yong
Huang, Ling-ling
Zhang, Xian
Luo, Hong
Wu, Su-ying
Lyu, Hai-yan
Huang, Li-huan
Xu, Huaxi
Zhang, Yun-wu
author_facet Liu, Fa-rong
Zhou, Yunqiang
Wang, Yong
Huang, Ling-ling
Zhang, Xian
Luo, Hong
Wu, Su-ying
Lyu, Hai-yan
Huang, Li-huan
Xu, Huaxi
Zhang, Yun-wu
author_sort Liu, Fa-rong
collection PubMed
description Bipolar disorder (BD) is a complex psychiatric disorder with strong heritability. Identification of new BD risk genes will help determine the mechanism underlying disease pathogenesis. In the present study, we carried out whole genome sequencing for a Chinese BD family with three affected members and three unaffected members, and identified multiple candidate causal variations, including a frameshift mutation in the GOLGB1 gene. Since a GOLGB1 missense mutation was also found in another BD pedigree, we carried out functional studies by downregulating Golgb1 expression in the brain of neonatal mice. Golgb1 deficiency had no effect on anxiety, memory, and social behaviors in young adult mice. However, we found that young adult mice with Golgb1 deficiency exhibited elevated locomotor activity and decreased depressive behaviors in the tail suspension test and the sucrose preference test, but increased depressive behaviors in the forced swim test, resembling the dual character of BD patients with both mania and depression. Moreover, Golgb1 downregulation reduced PSD93 levels and Akt phosphorylation in the brain. Together, our results indicate that GOLGB1 is a strong BD risk gene candidate whose deficiency may result in BD phenotypes possibly through affecting PSD93 and PI3K/Akt signaling.
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spelling pubmed-94826262022-09-19 Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder Liu, Fa-rong Zhou, Yunqiang Wang, Yong Huang, Ling-ling Zhang, Xian Luo, Hong Wu, Su-ying Lyu, Hai-yan Huang, Li-huan Xu, Huaxi Zhang, Yun-wu Transl Psychiatry Article Bipolar disorder (BD) is a complex psychiatric disorder with strong heritability. Identification of new BD risk genes will help determine the mechanism underlying disease pathogenesis. In the present study, we carried out whole genome sequencing for a Chinese BD family with three affected members and three unaffected members, and identified multiple candidate causal variations, including a frameshift mutation in the GOLGB1 gene. Since a GOLGB1 missense mutation was also found in another BD pedigree, we carried out functional studies by downregulating Golgb1 expression in the brain of neonatal mice. Golgb1 deficiency had no effect on anxiety, memory, and social behaviors in young adult mice. However, we found that young adult mice with Golgb1 deficiency exhibited elevated locomotor activity and decreased depressive behaviors in the tail suspension test and the sucrose preference test, but increased depressive behaviors in the forced swim test, resembling the dual character of BD patients with both mania and depression. Moreover, Golgb1 downregulation reduced PSD93 levels and Akt phosphorylation in the brain. Together, our results indicate that GOLGB1 is a strong BD risk gene candidate whose deficiency may result in BD phenotypes possibly through affecting PSD93 and PI3K/Akt signaling. Nature Publishing Group UK 2022-09-17 /pmc/articles/PMC9482626/ /pubmed/36115840 http://dx.doi.org/10.1038/s41398-022-02163-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Fa-rong
Zhou, Yunqiang
Wang, Yong
Huang, Ling-ling
Zhang, Xian
Luo, Hong
Wu, Su-ying
Lyu, Hai-yan
Huang, Li-huan
Xu, Huaxi
Zhang, Yun-wu
Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder
title Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder
title_full Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder
title_fullStr Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder
title_full_unstemmed Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder
title_short Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder
title_sort pedigree-based study to identify golgb1 as a risk gene for bipolar disorder
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9482626/
https://www.ncbi.nlm.nih.gov/pubmed/36115840
http://dx.doi.org/10.1038/s41398-022-02163-x
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