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Principal Investigator: James Joseph Crowley
Organization: UNIV OF NORTH CAROLINA CHAPEL HILL
Fiscal Year: 2024
Award: $194,375
Funding agency: National Institute of Mental Health
Project Summary
In this study we seek to understand how rare genetic variation in all protein coding genes (the exome)
influences the risk of developing obsessive-compulsive disorder (OCD). OCD is of major public health
importance owing to its profound personal and societal costs. Little is known for certain about its etiology, and
treatment, detection and prevention strategies are not optimal or directed by knowledge of pathophysiology. In
other psychiatric disorders (e.g., autism, intellectual disability, schizophrenia, ADHD), whole exome
sequencing (WES) in large numbers of subjects 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 number of OCD subjects with
WES data, in a first step toward elucidating the fundamental biology of this condition.
Three overlapping areas will be investigated in this project. First, we will produce WES data from 5,100
OCD subjects and 3,000 ancestry-matched controls, all from Sweden and Norway. Sequencing individuals
from these countries provides the substantial advantage of knowing about co-morbid conditions. We will call
rare genetic variation from the sequencing data. Second, we will combine these new data with existing WES
data for ~1,400 OCD cases and ~8,000 controls. This will increase power to identify OCD risk genes, which we
will do using a combination of existing and novel analytical methods. Third, we will further refine our
understanding of the genetic architecture of OCD, focusing on the relationship of OCD risk to risk for other
neurodevelopmental disorders, including tic disorders, autism, ADHD, schizophrenia and bipolar disorder.
Combining WES data from multiple large studies will enhance power to identify shared loci and begin to
identify loci with greater specificity for OCD. Overall, we believe this study will improve our understanding of
genetic risk factors for OCD, with a view towards improving clinical outcomes and reducing chronicity and
societal costs.
Terms: <0-11 years old><AD/HD><ADHD><ASD><Active Follow-up><Adolescent><Adolescent Youth><Affect><Amino Acid Sequence Determinations><Area><Attention deficit hyperactivity disorder><Autism><Autistic Disorder><Awareness><Biological><Biology><Bipolar Affective Psychosis><Bipolar Disorder><Causality><Child><Child Youth><Children (0-21)><Chronic><Clinical><Code><Coding System><Collaborations><Collection><Complex><Copy Number Polymorphism><Country><DNA><DNA Resequencing><Data><Data Set><Deoxyribonucleic Acid><Detection><Development><Disease><Disorder><Dysfunction><Early Infantile Autism><Environmental Factor><Environmental Risk Factor><Etiology><Functional disorder><Gene Copy Number><Gene Dosage><Gene Expression><Genes><Genetic><Genetic Diversity><Genetic Risk><Genetic Variation><Genetic predisposing factor><Genome><Genotype><Gilles de la Tourette syndrome><Gilles de la Tourette's Disease><Goals><Guinon's disease><Hereditary><Human><Individual><Infantile Autism><Inherited><Intellectual disability><Intellectual functioning disability><Intellectual limitation><Kanner's Syndrome><Knowledge><Learning><Manic-Depressive Psychosis><Mental disorders><Mental health disorders><Methods><Modern Man><Molecular><Molecular Target><Neurodevelopmental Disorder><Neurological Development Disorder><Norway><Nucleotides><Obsessive compulsive behavior><Obsessive-Compulsive Disorder><Obsessive-Compulsive Neurosis><Outcome><Parents><Pathway interactions><Peptide Sequence Determination><Physiopathology><Play><Population><Predominantly Hyperactive-Impulsive Type Attention-Deficit Disorder><Predominantly Hyperactive-Impulsive Type Hyperactivity Disorder><Preventative strategy><Prevention strategy><Preventive strategy><Price><Protein Sequence Determinations><Protein Sequencing><Protein Sequencing Molecular Biology><Proteins><Psychiatric Diagnosis><Psychiatric Disease><Psychiatric Disorder><Psychiatrist><Public Health><Publishing><Research><Resequencing><Risk><Risk-associated variant><Role><Sampling><Schizophrenia><Schizophrenic Disorders><Site><Specificity><Sweden><System><Tic Disorder, Combined Vocal and Multiple Motor><Tic disorder><Tourette Syndrome><Tourette's><Tourette's Disease><Tourette's Disorder><Tourette's Syndrome><Transmission><Variant><Variation><active followup><analytical method><autism spectral disorder><autism spectrum disorder><autistic spectrum disorder><biologic><bipolar affective disorder><bipolar disease><bipolar illness><bipolar mood disorder><case control><case-controlled><causation><cell type><co-morbid><co-morbidity><comorbidity><copy number variant><copy number variation><dementia praecox><developmental><discover genes><disease causation><disease risk><disorder risk><environmental risk><exome><exome sequencing><exome-seq><exomes><follow up><follow-up><followed up><followup><gene discovery><genetic architecture><genetic risk factor><genome scale><genome-wide><genomewide><improved><indel><inherited factor><insertion-deletion><insertion-deletion mutation><insertion/deletion><insertion/deletion mutation><intellectual and developmental disability><juvenile><juvenile human><kids><limited intellectual functioning><maladie des tics><manic depressive disorder><manic depressive illness><mental illness><method development><neurodevelopmental disease><neuropsychiatric><neuropsychiatry><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><non-genetic><nongenetic><novel><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><obsessive compulsive><parent><pathophysiology><pathway><phenotypic data><power analysis><pricing><psychiatric co-morbidity><psychiatric comorbidity><psychiatric genomics><psychiatric illness><psychological disorder><risk allele><risk gene><risk genotype><risk loci><risk locus><risk variant><schizophrenic><skills><social role><societal costs><tic de Guinon><tic related><transmission process><youngster>