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对异质种群大鼠在旷场中测试的三种行为进行全基因组关联研究,发现了与精神疾病相关的多个基因座。

Genome-Wide Association Study on Three Behaviors Tested in an Open Field in Heterogeneous Stock Rats Identifies Multiple Loci Implicated in Psychiatric Disorders.

作者信息

Gunturkun Mustafa Hakan, Wang Tengfei, Chitre Apurva S, Garcia Martinez Angel, Holl Katie, St Pierre Celine, Bimschleger Hannah, Gao Jianjun, Cheng Riyan, Polesskaya Oksana, Solberg Woods Leah C, Palmer Abraham A, Chen Hao

机构信息

Department of Pharmacology, Addiction Science and Toxicology, University of Tennessee Health Science Center, Memphis, TN, United States.

Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.

出版信息

Front Psychiatry. 2022 Feb 14;13:790566. doi: 10.3389/fpsyt.2022.790566. eCollection 2022.

Abstract

Many personality traits are influenced by genetic factors. Rodents models provide an efficient system for analyzing genetic contribution to these traits. Using 1,246 adolescent heterogeneous stock (HS) male and female rats, we conducted a genome-wide association study (GWAS) of behaviors measured in an open field, including locomotion, novel object interaction, and social interaction. We identified 30 genome-wide significant quantitative trait loci (QTL). Using multiple criteria, including the presence of high impact genomic variants and co-localization of cis-eQTL, we identified 17 candidate genes () for these traits. Many of these genes have been implicated by human GWAS of various psychiatric or drug abuse related traits. In addition, there are other candidate genes that likely represent novel findings that can be the catalyst for future molecular and genetic insights into human psychiatric diseases. Together, these findings provide strong support for the use of the HS population to study psychiatric disorders.

摘要

许多人格特质受遗传因素影响。啮齿动物模型为分析这些特质的遗传贡献提供了一个有效的系统。我们使用1246只青春期异质种群(HS)雄性和雌性大鼠,对在旷场中测量的行为进行了全基因组关联研究(GWAS),这些行为包括运动、新物体交互和社交互动。我们鉴定出30个全基因组显著的数量性状基因座(QTL)。使用多种标准,包括高影响基因组变异的存在和顺式eQTL的共定位,我们鉴定出了这些性状的17个候选基因。其中许多基因已在人类对各种精神或药物滥用相关特质的GWAS中被提及。此外,还有其他候选基因可能代表新发现,可成为未来对人类精神疾病进行分子和遗传洞察的催化剂。总之,这些发现为使用HS种群研究精神疾病提供了有力支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67b3/8882588/f66aaf178521/fpsyt-13-790566-g0001.jpg

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