Multi-pronged genetic studies of schizophrenia in an inbred population

近交群体精神分裂症的多管齐下遗传学研究

• 批准号: 8731970
• 负责人: Hader A. Mansour
• 金额: $ 47.6万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-20 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8731970
• 关键词: Affect; Arabs; Area; Autistic Disorder; Bioinformatics; Caucasians; Caucasoid Race; Chromosome Mapping; Clinical; Clinical Investigator; Communities; Complement; Complex; Computer software; Consanguinity; Consent; Consultations; Data; Disease; Egypt; Ethnic group; Etiology; Exhibits; Family; Genes; Genetic; Genetic Polymorphism; Genetic Research; Genetic Risk; Genomics; Genotype; Goals; Grant; Hereditary Disease; Heritability; Inbreeding; Individual; Inheritance Patterns; Institution; Intellectual functioning disability; Investigation; Knowledge; Laboratories; Lead; Maps; Medicine; Middle East; Molecular Genetics; Mutation; National Institute of Mental Health; Odds Ratio; Paper; Participant; Pathogenesis; Pathway interactions; Patients; Plant Roots; Population; Predisposition; Psychiatric Diagnosis; Public Health; Publishing Peer Reviews; Relative (related person); Research; Research Infrastructure; Research Personnel; Research Project Grants; Risk; Sampling; Schizophrenia; Source; Structure; Testing; Training; United States National Institutes of Health; Universities; Variant; Work; base; cognitive function; design; follow-up; genetic risk factor; improved; insight; interest; member; next generation sequencing; novel; repository; response; risk variant; success; tool

DESCRIPTION (provided by applicant): Schizophrenia (SZ) is a common, lifelong, disabling disorder. Its treatment remains unsatisfactory across the world. Thus, research into its causation and pathogenesis is needed urgently. Based on the substantial heritability (~70%), gene mapping efforts are in progress. Credible risk variants have been found, but the identified factors explain only a small proportion of the estimated heritability. Even the limited information has highlighted novel pathways for SZ genesis, so additional gene mapping studies are warranted. Such efforts will require many thousands of participants in outbred populations. Our plan with an inbred population promises novel insights with more modest effort. We will build on a collaborative R21 project between investigators at the University of Pittsburgh (PITT) and Mansoura University (MU, Egypt). In the Nile delta region, we have found increased consanguinity among patients with SZ compared with unaffected controls. The results are consistent with recessive genetic risk factors for SZ. We will employ a powerful tool called homozygosity by descent (HBD) analysis that has been successfully used to map several hundred recessive Mendelian diseases and genetically more complex disorders like autism and intellectual disability. Our preliminary studies suggest similar success for SZ. Our proposal is novel also because most SZ gene mapping studies have been conducted among Caucasian ancestry participants. Investigations of other ethnic groups, particularly those with unusual patterns of inheritance may yield useful, complementary insights. Through the NIMH genetics repository, we will share samples and data with members of the scientific community, further increasing the impact of our work. There is increasing interest in harnessing genomics research, as well as recognition of the

描述（由申请人提供）：精神分裂症（SZ）是一种常见的，终生的残疾障碍。它的治疗在世界范围内仍然不令人满意。因此，紧急需要研究其因果关系和发病机理。基于实质性的遗传力（〜70％），基因映射工作正在进行中。已经发现了可靠的风险变体，但是确定的因素仅解释了估计遗传力的一小部分。甚至有限的信息 已经强调了SZ Genesis的新型途径，因此有必要进行其他基因映射研究。这样的努力将需要数千名在近亲人群中的参与者。我们与近交的计划有望以更适度的努力来提供新颖的见解。我们将在匹兹堡大学（皮特）和曼苏拉大学（埃及MU）的调查人员之间进行合作R21项目。在尼罗河三角洲地区，与未受影响的对照相比，我们发现SZ患者的血缘气质增加。结果与SZ的隐性遗传危险因素一致。我们将通过下降（HBD）分析采用一种称为纯合性的工具，该工具已成功地用于绘制几百个隐性孟德尔疾病，并在遗传上更复杂的疾病（如自闭症和智力障碍）。我们的初步研究表明SZ的成功类似。我们的建议之所以新颖，是因为大多数SZ基因映射研究都是在高加索血统参与者中进行的。对其他种族，特别是那些具有不寻常的继承模式的族裔的调查可能会产生有用的补充见解。通过NIMH遗传学存储库，我们将与科学界的成员共享样本和数据，从而进一步增加我们工作的影响。对利用基因组学研究以及认识的兴趣越来越大