Epigenetics and disease: the role of DNA methylation in schizophrenia susceptibil

表观遗传学与疾病：DNA 甲基化在精神分裂症易感性中的作用

• 批准号: 7726401
• 负责人: Roel A Ophoff
• 金额: $ 49.99万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726401
• 关键词: Age; Base Sequence; Biochemical; Brain region; Chromosome Structures; Classification; Complex; DNA Methylation; DNA Modification Process; DNA Sequence; Disease; Disease susceptibility; Epigenetic Process; Gender; Genes; Genetic; Human Genome; Lead; Mental disorders; Modification; Molecular; Mutation; Pathway interactions; Patients; Phase; Play; Predisposition; Role; Schizophrenia; Signal Transduction; Site; Validation; base; cohort; comparative; genome wide association study; genome-wide; public health relevance; trait

DESCRIPTION (provided by applicant): Most psychiatric disorders are not due to mutations in a single gene but rather involve cellular pathways under control of many genes and molecular signals. Recent studies point to the fact that complex epigenetic mechanisms regulating gene activity 'above' the genetic nucleotide sequence may be involved as well. The best understood mechanism of epigenetic modification is DNA methylation. In this genome-wide study we will examine the role of DNA methylation in schizophrenia susceptibility. Our study consists of a genome-wide discovery and replication phase to identify CpG loci in the human genome that are under epigenetic control and involved in disease susceptibility, followed by locus-specific validation in large schizophrenia cohorts. Our systematic approach for identifying candidate CpG loci involved in disease also includes study of general features of DNA methylation such as age, gender and genetic controls. The genome-wide effort with comparative analyses of multiple brain regions of patients and controls will provide a unique opportunity to establish what role DNA methylation plays in vulnerability to develop schizophrenia and perhaps other psychiatric traits. Public Health Relevance: Biochemical modifications of DNA and chromosome structure provide heritable information that is not encoded in the DNA sequence itself, but is likely to play a role in disease susceptibility. We will screen the human genome of schizophrenia patients and unaffected control subjects in order to identify these sites involved in disease. This will lead to a better understanding of the genetic basis of schizophrenia.

描述（由申请人提供）：大多数精神疾病不是由于单个基因的突变，而是涉及许多基因和分子信号控制下的细胞途径。最近的研究指出，复杂的表观遗传机制调节基因的活性'以上'的遗传核苷酸序列可能也参与其中。表观遗传修饰的最佳理解机制是DNA甲基化。在这项全基因组研究中，我们将研究DNA甲基化在精神分裂症易感性中的作用。我们的研究包括全基因组发现和复制阶段，以确定人类基因组中受表观遗传控制并参与疾病易感性的CpG位点，然后在大型精神分裂症队列中进行位点特异性验证。我们的系统方法，用于确定候选CpG位点参与疾病还包括研究的一般特征的DNA甲基化，如年龄，性别和遗传控制。对患者和对照组的多个大脑区域进行比较分析的全基因组努力将提供一个独特的机会，以确定DNA甲基化在发展精神分裂症和其他精神病特征的脆弱性中起着什么作用。公共卫生相关性：DNA和染色体结构的生化修饰提供了DNA序列本身不编码的可遗传信息，但可能在疾病易感性中发挥作用。我们将筛选精神分裂症患者和未受影响的对照受试者的人类基因组，以确定与疾病有关的这些位点。这将有助于更好地了解精神分裂症的遗传基础。