药物发现与精神分裂症的遗传学和生物学基础

IF 6.1 2区 医学 Q1 CLINICAL NEUROLOGY European Neuropsychopharmacology Pub Date : 2024-10-01 DOI:10.1016/j.euroneuro.2024.08.042
David Collier
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引用次数: 0

摘要

全基因组关联和罕见基因变异分析为研究精神分裂症的遗传基础提供了重要依据,目前已发现 250 多种变异。有证据表明,基因与疾病相关的遗传学证据(即使是低风险、常见的变异)将药物靶点的成功概率提高了两倍或更多(Minikel 等人,2024 年)。然而,利用这些信息进行药物开发还存在一些障碍,包括变异基因间的映射、目标优先级的确定、疾病模型的有效性、目标的可及性以及治疗假设的提出。从好的方面来看,这些基因座内的基因图谱已经确定了多巴胺 D2 受体(DRD2)基因,这是典型抗精神病药物的一个主要靶点,还确定了产生可药物治疗或潜在药物治疗蛋白的许多其他基因(Kraft 等人,2024 年)。本讲座将探讨利用遗传学和基因组学进行药物开发和分层的潜在途径。
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Drug Discovery and the Genetic and Biological Underpinnings of Schizophrenia
Genome-wide association and the analysis of rare genetic variants has provided great insights into the genetic basis of schizophrenia, with over 250 variants now identified. Evidence suggests that genetic evidence for association between a gene and disease (even for low risk, common variants) increased the probability of success as a drug target by two-fold or more (Minikel et al., 2024). However, there are several barriers to drug development using this information, including variant-to-gene mapping, target prioritisation, the validity of disease models, target tractability and the development of a therapeutic hypothesis. On the plus side, mapping of the genes within these loci have identified the dopamine D2 receptor (DRD2) gene, a major target of typical antipsychotic drugs, as well as a number of other genes that produce druggable or potentially druggable proteins (Kraft et al., 2024). In this presentation, potential pathways to drug development and stratification using genetics and genomics will be explored.
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来源期刊
European Neuropsychopharmacology
European Neuropsychopharmacology 医学-精神病学
CiteScore
10.30
自引率
5.40%
发文量
730
审稿时长
41 days
期刊介绍: European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.
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