OCD: Novel Comparative Genomic Approaches to Identify Disease and Treatment Mechanisms

OCD：识别疾病和治疗机制的新比较基因组方法

• 批准号: 9156382
• 负责人: James Joseph Crowley
• 金额: $ 65.09万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9156382
• 关键词: Animal Model; Architecture; Area; Autistic Disorder; Biological; Biology; Bipolar Disorder; Canis familiaris; Clinic; Clinical; Complex; Copy Number Polymorphism; Custom; DNA; Data; Detection; Dimensions; Discipline of obstetrics; Disease; Drug Targeting; Environment; Environmental Risk Factor; Epidemiology; Etiology; Face; Family; Functional disorder; Genes; Genetic; Genetic Risk; Genetic study; Genomic approach; Genomics; Genotype; Goals; Hereditary Disease; Human; Individual; Intervention; Knowledge; Learning; Life; Link; Measures; Medical Genetics; Mental disorders; Meta-Analysis; Morbidity - disease rate; Norway; Obsessive-Compulsive Disorder; Outcome; Paternal Age; Pathway interactions; Phenotype; Prevention strategy; Public Health; Publishing; Recording of previous events; Resources; Risk; Sample Size; Sampling; Scandinavian; Schizophrenia; Societies; Socioeconomic Status; Source; Specialist; Sweden; Symptoms; Testing; Treatment outcome; United States National Institutes of Health; Update; Variant; associated symptom; base; case control; comparative genomics; cost; cost effective; design; disability; disorder risk; early onset; exome; follow-up; gene environment interaction; genetic risk factor; genome wide association study; genomic data; improved; neuropsychiatry; novel; predict clinical outcome; response; risk variant; sample collection; tic-related; trait; treatment response

PROJECT SUMMARY In this study we seek to understand how genetic and environmental factors jointly influence both the risk of developing Obsessive-Compulsive Disorder (OCD) and the outcome of treatment interventions. OCD and related disorders are of major public health importance owing to their profound personal and societal costs. Little is known for certain about their etiology, and treatment, detection and prevention strategies are not optimal or directed by knowledge of pathophysiology. In other psychiatric disorders (e.g., schizophrenia, bipolar disorder and autism), genomics has begun to deliver fundamental knowledge about genetic architecture, identify specific loci for biological follow-up and localize pathways altered in disease. We intend to realize these same advances for OCD by markedly increasing the worldwide sample size for genomic analysis, in a first step toward elucidating the fundamental biology of this condition. Three overlapping areas will be investigated in this project. First, we will collect the world's largest richly phenotyped sample of OCD cases (N = 10,000). To do this in an efficient and cost-effective manner, we will take advantage of an ongoing nationwide OCD treatment study in Norway and a network of active OCD clinics in Sweden. The phenotypes will include a detailed clinical characterization (e.g., comorbidities, symptom dimensions, treatment response) and links to the Swedish and Norwegian registers, facilitating gene by environment interaction studies. Second, we will genotype all 10,000 samples on the PsychChip GWAS array (genotypes for >30,000 matched controls are already available). This will allow us to discover genomic loci harboring common and rare variation associated with OCD. We will also incorporate a novel comparative genomic approach to interpret these genomic data, capitalizing on an animal model with high face and construct validity: canine compulsive disorder. Third, we will calculate individual risk profile scores (GRS) as a measure of genetic liability to OCD and test for interactions between genetic liability and a range of clinical (e.g., response to treatment), epidemiological (e.g., paternal age, obstetric complications, early life adversity, socioeconomic status) and genetic epidemiological (e.g., family history) variables from the Swedish and Norwegian registers. We expect this study to improve our understanding of the causal mechanisms implicated in OCD, with a view towards improving clinical outcomes and reducing chronicity and societal costs.

项目总结