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一般认知功能与精神分裂症的遗传重叠:认知 GWAS 的综述。

Genetic Overlap between General Cognitive Function and Schizophrenia: A Review of Cognitive GWASs.

机构信息

Department of Neuropsychiatry, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.

Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan.

出版信息

Int J Mol Sci. 2018 Nov 30;19(12):3822. doi: 10.3390/ijms19123822.

Abstract

General cognitive (intelligence) function is substantially heritable, and is a major determinant of economic and health-related life outcomes. Cognitive impairments and intelligence decline are core features of schizophrenia which are evident before the onset of the illness. Genetic overlaps between cognitive impairments and the vulnerability for the illness have been suggested. Here, we review the literature on recent large-scale genome-wide association studies (GWASs) of general cognitive function and correlations between cognitive function and genetic susceptibility to schizophrenia. In the last decade, large-scale GWASs ( > 30,000) of general cognitive function and schizophrenia have demonstrated that substantial proportions of the heritability of the cognitive function and schizophrenia are explained by a polygenic component consisting of many common genetic variants with small effects. To date, GWASs have identified more than 100 loci linked to general cognitive function and 108 loci linked to schizophrenia. These genetic variants are mostly intronic or intergenic. Genes identified around these genetic variants are densely expressed in brain tissues. Schizophrenia-related genetic risks are consistently correlated with lower general cognitive function ( = -0.20) and higher educational attainment ( = 0.08). Cognitive functions are associated with many of the socioeconomic and health-related outcomes. Current treatment strategies largely fail to improve cognitive impairments of schizophrenia. Therefore, further study is needed to understand the molecular mechanisms underlying both cognition and schizophrenia.

摘要

一般认知(智力)功能在很大程度上是遗传的,是经济和与健康相关的生活结果的主要决定因素。认知障碍和智力下降是精神分裂症的核心特征,在疾病发作之前就已经明显。有人提出认知障碍与疾病易感性之间存在遗传重叠。在这里,我们回顾了最近关于一般认知功能的全基因组关联研究(GWAS)和认知功能与遗传易感性之间与精神分裂症的相关性的文献。在过去的十年中,针对一般认知功能和精神分裂症的大规模 GWAS(> 30,000)表明,认知功能和精神分裂症的遗传率的很大一部分是由许多具有小效应的常见遗传变异组成的多基因成分解释的。迄今为止,GWAS 已经确定了 100 多个与一般认知功能相关的基因座和 108 个与精神分裂症相关的基因座。这些遗传变异大多位于内含子或基因间区。围绕这些遗传变异鉴定的基因在脑组织中密集表达。与精神分裂症相关的遗传风险与较低的一般认知功能(= -0.20)和较高的受教育程度(= 0.08)一致相关。认知功能与许多社会经济和与健康相关的结果相关。目前的治疗策略在很大程度上未能改善精神分裂症的认知障碍。因此,需要进一步研究以了解认知和精神分裂症的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b53/6320986/57947926d591/ijms-19-03822-g001.jpg

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