Next generation risk variant discovery in a highly penetrant OCD subtype

高渗透性强迫症亚型的下一代风险变异发现

• 批准号: 8166327
• 负责人: ERIKA L NURMI
• 金额: $ 18.04万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-18 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166327
• 关键词: Alleles; Award; Biological Models; Candidate Disease Gene; Child Psychiatry; Chromosome Mapping; Clinical Data; Code; Complex; Computing Methodologies; Data; Data Set; Databases; Disease; Family; Family Study; Future; Genes; Genetic; Genome; Goals; Hereditary Disease; Heterogeneity; In Vitro; Informatics; Knowledge; Laboratories; Learning; Machine Learning; Maps; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Methodology; Methods; Molecular; Molecular Diagnosis; Molecular Genetics; Obsessive-Compulsive Disorder; Open Reading Frames; Pathway interactions; Phenotype; Pilot Projects; Positioning Attribute; Predisposition; Principal Investigator; Proteins; Recruitment Activity; Research; Research Activity; Research Design; Research Personnel; Research Support; Resolution; Risk; Sampling; Supervision; Technology; Tic disorder; Training; Variant; base; career; career development; clinical phenotype; disorder subtype; exome; experience; follow-up; genetic technology; genome sequencing; innovation; meetings; neuropsychiatry; next generation; novel; proband; programs; psychogenetics; research and development; segregation; skills; tool; trait

DESCRIPTION (provided by applicant): The proposed five-year K23 Mentored Patient-Oriented Research Career Development Award outlines a program of career development and research activities that will assist the principal investigator to transition to an independent research career and prepare her to tackle the challenges ahead in unraveling the genetic basis of complex psychiatric phenotypes. The innovative research plan details an approach to mapping risk for a strongly genetic subtype of obsessive compulsive (OCD) and comorbid tic disorders by generating and analyzing whole-exome sequence in select families to identify risk alleles. These efforts will be guided by pilot identity-by-descent, homozygosity, and copy number variant data in the comprehensively phenotyped OCD Collaborative Genetic Study (OCGS) multiplex family dataset. The OCD+tic phenotype is an ideal complex disorder for next generation genetic mapping. The clear phenotype, possibly reduced heterogeneity, and strong genetic effects make it an excellent candidate for the application of methodologies recently proven successful in Mendelian disorders. While the principle investigator has a strong background in child psychiatry and molecular genetics, the knowledge and skills required to master emerging genetic technologies such as next generation sequencing (NGS) are novel and complex. The short-term goals of this application are to gain proficiency in the methods that will drive the field over the coming decades, learn the statistical, computational, and informatics tools that will support this research, continue to develop skills in study design and interpretation, and refine and incorporate clinical and phenotyping skills. A program of coursework, supervision, and hands-on application of these approaches will equip the applicant in the long-term to integrate molecular, computational, and phenotypic data to make meaningful contributions to the field of psychiatric genetics. This award will help the candidate to establish an independent research career, position herself on the front of these new advances, and bring the lessons learned to the field of child psychiatry. PUBLIC HEALTH RELEVANCE: The proposed five-year K23 Mentored Patient-Oriented Research Career Development Award outlines a program of career development and research activities that will assist the principal investigator to transition to an independent research career and prepare her to tackle the challenges ahead in unraveling the genetic basis of complex psychiatric traits. The innovative research plan details an approach to finding risk genes for a strongly genetic subtype of obsessive compulsive (OCD) and comorbid tic disorders by analyzing the full protein-coding sequence of the genome in select families of the comprehensively characterized OCD Collaborative Genetic Study (OCGS). A program of coursework, supervision, and hands-on application of these approaches will equip the applicant in the long-term to integrate molecular, computational, and clinical data to make meaningful contributions to the field of psychiatric genetics.

描述（由申请人提供）：拟议的为期五年的 K23 指导患者导向研究职业发展奖概述了职业发展和研究活动计划，该计划将帮助主要研究者过渡到独立研究职业，并为她应对挑战做好准备在揭示复杂精神病表型的遗传基础方面处于领先地位。这项创新研究计划详细介绍了一种方法，通过生成和分析选定家族的全外显子序列来识别风险等位基因，来绘制强迫症（OCD）和共病抽动障碍的强遗传亚型的风险图谱。这些工作将以全面表型强迫症协作遗传研究 (OCGS) 多重家族数据集中的试点身份血统、纯合性和拷贝数变异数据为指导。 OCD+抽动表型是下一代遗传图谱的理想复杂疾病。清晰的表型、可能减少的异质性和强大的遗传效应使其成为最近证明成功治疗孟德尔疾病的方法的绝佳候选者。虽然主要研究者在儿童精神病学和分子遗传学方面拥有深厚的背景，但掌握下一代测序 (NGS) 等新兴遗传技术所需的知识和技能是新颖且复杂的。该应用程序的短期目标是熟练掌握未来几十年推动该领域发展的方法，学习支持该研究的统计、计算和信息学工具，继续发展研究设计和解释方面的技能，并完善和整合临床和表型分析技能。这些方法的课程作业、监督和实践应用计划将使申请人能够长期整合分子、计算和表型数据，为精神遗传学领域做出有意义的贡献。该奖项将帮助候选人建立独立的研究生涯，将自己置于这些新进展的前沿，并将学到的经验教训带到儿童精神病学领域。 公共卫生相关性：拟议的五年期 K23 以患者为导向的研究职业发展奖概述了职业发展和研究活动计划，该计划将帮助主要研究者过渡到独立研究职业，并为她应对未来的挑战做好准备复杂精神特征的遗传基础。这项创新研究计划详细介绍了一种方法，通过分析全面表征的强迫症协作遗传研究 (OCGS) 选定家族的基因组完整蛋白质编码序列，寻找强迫症 (OCD) 和共病抽动障碍的强遗传亚型的风险基因。 ）。这些方法的课程作业、监督和实践应用计划将使申请人能够长期整合分子、计算和临床数据，为精神遗传学领域做出有意义的贡献。