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: 8410815
• 负责人: Hader A. Mansour
• 金额: $ 58.23万
• 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/8410815
• 关键词: Affect; Alleles; 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; Funding; 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; Publishing Peer Reviews; Relative (related person); Research; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Risk; Sampling; Schizophrenia; Source; Structure; Testing; Training; United States National Institutes of Health; Universities; Variant; Work; base; cognitive function; design; follow-up; genetic analysis; genetic risk factor; improved; insight; interest; member; next generation; novel; public health relevance; repository; response; scale up; 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 public health relevance of consanguinity in the Middle East. Accordingly, we have trained and assisted our Egyptian colleagues to establish a genetics research group at MU, including a molecular genetics laboratory. We have published our work and obtained other funds to start additional research. Thus, we have successfully used our research as a vehicle for research infrastructure and capacity building at MU. Our goal is to scale up the genetics research at MU by implementing state of the art genetic analyses, including computing and bioinformatics. The resources and expertise garnered through this work will facilitate research into other diseases. PUBLIC HEALTH RELEVANCE: Schizophrenia is a common, severe, world-wide disorder for which treatment is presently inadequate. The origins of this disorder are unknown. Knowledge about the root causes of schizophrenia will help us to understand the origins of this devastating disorder and could also help us to design more effective medicines. Our studies will focus on genetic risk factors for schizophrenia in Egypt. Our studies will benefit from the structure of locl communities, including large, cooperative families. They will enable local research infrastructure and capacity building work and will complement ongoing work in the USA. Thus our studies are relevant not only for Egyptians, but also for US citizens.

描述（由申请人提供）：精神分裂症（SZ）是一种常见的终身致残障碍。世界各地对艾滋病的治疗仍不令人满意。因此，迫切需要对其病因和发病机制进行研究。基于大量的遗传率（约70%），基因定位工作正在进行中。可信的风险变异已被发现，但已确定的因素只能解释估计遗传力的一小部分。即使信息有限