Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings

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	Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings
	Li, M; Li, T; Xiao, X; Chen, J; Hu, ZH; Fang, YR
	2022
发表期刊	MOLECULAR PSYCHIATRY
ISSN	1359-4184
卷号	27 期号:7 页码:2927-2939
摘要	Genome-wide association studies (GWAS) have reported substantial genomic loci significantly associated with clinical risk of bipolar disorder (BD), and studies combining techniques of genetics, neuroscience, neuroimaging, and pharmacology are believed to help tackle clinical problems (e.g., identifying novel therapeutic targets). However, translating findings of psychiatric genetics into biological mechanisms underlying BD pathogenesis remains less successful. Biological impacts of majority of BD GWAS risk loci are obscure, and the involvement of many GWAS risk genes in this illness is yet to be investigated. It is thus necessary to review the progress of applying BD GWAS risk genes in the research and intervention of the disorder. A comprehensive literature search found that a number of such risk genes had been investigated in cellular or animal models, even before they were highlighted in BD GWAS. Intriguingly, manipulation of many BD risk genes (e.g., ANK3, CACNA1C, CACNA1B, HOMER1, KCNB1, MCHR1, NCAN, SHANK2 etc.) resulted in altered murine behaviors largely restoring BD clinical manifestations, including mania-like symptoms such as hyperactivity, anxiolytic-like behavior, as well as antidepressant-like behavior, and these abnormalities could be attenuated by mood stabilizers. In addition to recapitulating phenotypic characteristics of BD, some GWAS risk genes further provided clues for the neurobiology of this illness, such as aberrant activation and functional connectivity of brain areas in the limbic system, and modulated dendritic spine morphogenesis as well as synaptic plasticity and transmission. Therefore, BD GWAS risk genes are undoubtedly pivotal resources for modeling this illness, and might be translational therapeutic targets in the future clinical management of BD. We discuss both promising prospects and cautions in utilizing the bulk of useful resources generated by GWAS studies. Systematic integrations of findings from genetic and neuroscience studies are called for to promote our understanding and intervention of BD.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13743
专题	科研部门_转化基因组（李明）
推荐引用方式 GB/T 7714	Li, M,Li, T,Xiao, X,et al. Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings[J]. MOLECULAR PSYCHIATRY,2022,27(7):2927-2939.
APA	Li, M,Li, T,Xiao, X,Chen, J,Hu, ZH,&Fang, YR.(2022).Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings.MOLECULAR PSYCHIATRY,27(7),2927-2939.
MLA	Li, M,et al."Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings".MOLECULAR PSYCHIATRY 27.7(2022):2927-2939.

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