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: 8496119
• 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/8496119
• 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; exome sequencing; experience; follow-up; genetic technology; genome sequencing; innovation; meetings; neuropsychiatry; next generation; next generation sequencing; novel; proband; programs; psychogenetics; research and development; risk variant; 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.

描述（由申请人提供）：拟议的五年K23指导了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的计划，该计划将有助于首席研究人员过渡到独立研究职业，并准备应对挑战在揭示复杂精神病表型的遗传基础之前。创新的研究计划详细介绍了一种方法来绘制强烈的强迫性（OCD）和合并症的强烈遗传亚型，通过产生和分析选定家庭中的全结果序列以识别风险等位基因，以识别风险。这些努力将由逐个飞行型，纯合性和拷贝数变体数据的指导，在全面表型的OCD协作遗传研究（OCGS）多重族数据集中。 OCD+TIC表型是下一代遗传图的理想复杂障碍。明确的表型，可能降低了异质性和强大的遗传作用，使其成为应用方法在孟德尔疾病中成功使用方法的绝佳候选者。尽管原则研究者在儿童精神病学和分子遗传学方面具有强大的背景，但掌握新兴遗传技术（例如下一代测序（NGS））所需的知识和技能是新颖而复杂的。本应用程序的短期目标是熟练掌握将在未来几十年中推动该领域的方法，学习将支持这项研究的统计，计算和信息学工具，继续发展研究设计和解释方面的技能，并完善并融合了临床和表型技巧。这些方法的课程，监督和动手应用程序的计划将使申请人长期为分子，计算和表型数据整合，以对精神遗传学领域做出有意义的贡献。该奖项将有助于候选人建立独立的研究生涯，将自己定位在这些新进步前面，并将所吸取的教训带入儿童精神病学领域。