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采用连锁不平衡分数回归和全转录组关联研究评估左撇子与精神障碍的遗传相关性。

Evaluating the Genetic Correlations Between Left-Handedness and Mental Disorder Using Linkage Disequilibrium Score Regression and Transcriptome-Wide Association Study.

机构信息

Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, Key Laboratory of Environment and Genes Related to Diseases of Ministry of Education, Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk Road Region, School of Public Health, Health Science Center, Xi'an Jiaotong University, No. 76 Yan Ta West Road, Xi'an, 710061, People's Republic of China.

出版信息

Biochem Genet. 2020 Apr;58(2):348-358. doi: 10.1007/s10528-020-09952-3. Epub 2020 Feb 25.

Abstract

Handedness is an elusive human behavioral phenotypes and the genetic basis of it remains unclear until now. The aim of this study is to evaluate the genetic correlations between left-handedness and multiple mental disorders, and explored the genes detected by genetic correlations. In this study, linkage disequilibrium score regression (LDSC) analysis was conducted to evaluate the genetic correlations between left-handedness and multiple mental disorders. The significant genetic correlation was only observed between left-handedness and schizophrenia (SCZ). For the observed genetic correlation, transcriptome-wide association study (TWAS) was performed to identify the genes associated with left-handedness and SCZ, including brain RNA-seq (CBR) and brain RNA-seq splicing (CBRS). We detected several common genes associated with both left-handedness and SCZ, such as YWHAH, MAPT and ANO10. The common genes shared by left-handedness and SCZ were subjected to gene set enrichment analysis. Our study provides a novel clue for understanding the genetic correlation between left-handedness and SCZ.

摘要

惯用手是一种难以捉摸的人类行为表型,其遗传基础至今仍不清楚。本研究旨在评估左撇子与多种精神障碍之间的遗传相关性,并探讨遗传相关性检测到的基因。在这项研究中,进行了连锁不平衡评分回归(LDSC)分析,以评估左撇子与多种精神障碍之间的遗传相关性。仅观察到左撇子与精神分裂症(SCZ)之间存在显著的遗传相关性。对于观察到的遗传相关性,进行了全转录组关联研究(TWAS),以鉴定与左撇子和 SCZ 相关的基因,包括大脑 RNA 测序(CBR)和大脑 RNA 测序剪接(CBRS)。我们检测到了几个与左撇子和 SCZ 都相关的常见基因,例如 YWHAH、MAPT 和 ANO10。左撇子和 SCZ 共有的常见基因进行了基因集富集分析。我们的研究为理解左撇子和 SCZ 之间的遗传相关性提供了新的线索。

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