5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.
5. Collaborative Study on the Genetics of Alcoholism: Functional genomics.
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DOI：
10.1111/gbb.12855
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发表时间：
2023-10
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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作者：
酒精使用障碍是一种复杂的遗传性疾病，涉及遗传，神经和环境因素及其相互作用。酒精中毒遗传学合作研究（COGA）一直在调查这些因素，并通过全基因组关联研究确定了推定的酒精使用障碍风险基因。在这篇综述中，我们描述了COGA在阐明酒精使用障碍风险基因诱导的功能变化方面所取得的进展，使用多模式方法与人类细胞系和脑组织。这些研究涉及研究COGA参与者的淋巴母细胞和死后脑组织中的基因调控。高通量报告基因分析被用于鉴定单核苷酸多态性，其中替代等位基因在驱动基因表达方面不同。特定的单核苷酸多态性（编码或非编码）已被建模使用诱导多能干细胞来自COGA参与者，以评估遗传变异对转录组学的影响，神经元兴奋性，突触生理学，以及对乙醇的反应在人类神经元从个人和没有酒精使用障碍。我们对未来的研究提供了一个视角，例如使用多基因风险评分和诱导多能干细胞衍生的神经元群体来识别与酒精反应相关的信号通路。从与酒精使用障碍相关的基因或位点开始，COGA已经证明，COGA参与者和功能研究中多模态数据的整合可以揭示将基因组变异与酒精使用障碍联系起来的机制，以及未来治疗的潜在目标。酒精使用障碍是一种复杂的遗传性疾病，涉及遗传，神经和环境因素及其相互作用。酒精中毒遗传学合作研究（COGA）一直在调查这些因素，并通过全基因组关联研究确定了推定的酒精使用障碍风险基因。在这篇综述中，我们描述了COGA在阐明酒精使用障碍风险基因诱导的功能变化方面所取得的进展，使用多模式方法与人类细胞系和脑组织。
Alcohol Use Disorder is a complex genetic disorder, involving genetic, neural, and environmental factors, and their interactions. The Collaborative Study on the Genetics of Alcoholism (COGA) has been investigating these factors and identified putative alcohol use disorder risk genes through genome‐wide association studies. In this review, we describe advances made by COGA in elucidating the functional changes induced by alcohol use disorder risk genes using multimodal approaches with human cell lines and brain tissue. These studies involve investigating gene regulation in lymphoblastoid cells from COGA participants and in post‐mortem brain tissues. High throughput reporter assays are being used to identify single nucleotide polymorphisms in which alternate alleles differ in driving gene expression. Specific single nucleotide polymorphisms (both coding or noncoding) have been modeled using induced pluripotent stem cells derived from COGA participants to evaluate the effects of genetic variants on transcriptomics, neuronal excitability, synaptic physiology, and the response to ethanol in human neurons from individuals with and without alcohol use disorder. We provide a perspective on future studies, such as using polygenic risk scores and populations of induced pluripotent stem cell‐derived neurons to identify signaling pathways related with responses to alcohol. Starting with genes or loci associated with alcohol use disorder, COGA has demonstrated that integration of multimodal data within COGA participants and functional studies can reveal mechanisms linking genomic variants with alcohol use disorder, and potential targets for future treatments. Alcohol Use Disorder is a complex genetic disorder, involving genetic, neural, and environmental factors, and their interactions. The Collaborative Study on the Genetics of Alcoholism (COGA) has been investigating these factors and identified putative alcohol use disorder risk genes through genome‐wide association studies. In this review, we describe advances made by COGA in elucidating the functional changes induced by alcohol use disorder risk genes using multimodal approaches with human cell lines and brain tissue.
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遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
DOI：
10.1111/add.15697
发表时间：
2022-04
期刊：
Addiction (Abingdon, England)
影响因子：
--
作者：
Deak JD;Clark DA;Liu M;Schaefer JD;Jang SK;Durbin CE;Iacono WG;McGue M;Vrieze S;Hicks BM
通讯作者：
Hicks BM
影响因子：
6.9
作者：
Deak JD;Johnson EC
通讯作者：
Johnson EC
影响因子：
0.8
作者：
Dooves, Stephanie;Nadadhur, Aishwarya G.;Heine, Vivi M.
通讯作者：
Heine, Vivi M.
影响因子：
--
作者：
Cheng, Chialin;Fass, Daniel M;Haggarty, Stephen J
通讯作者：
Haggarty, Stephen J