This application describes a 5-year training program of didactic study, research mentoring and research activities focusing on the genetics of childhood obsessive-compulsive disorder (OCD). The training program will allow the candidate to gain expertise in methods of genetic research in complex disorders, including linkage, association and bioinformatics. The long-term objective of the career development plan is to extend the candidate's expertise in psychiatric phenotyping, statistical genetics and bioinformatics. To accomplish this goal, research activities will use the resources of the Johns Hopkins Department of Psychiatry for the understanding of the OCD phenotype; the Hopkins School of Public Health and National Human Genome Research Institute for bioinformatics, statistical genetics and genetic epidemiology training; and the Hopkins Genetics Core Lab facility for genotyping. Preliminary work includes the candidate's previous experience in a NIMH-funded family study of OCD with adult probands and pilot feasibility data from OCD child proband families. The research design consists of 2-stage sampling and psychiatric interviews of 80 OCD child probands and 720 first-, second-degree relatives. Probands are recruited by consecutive nonprobability sampling to maximize their utility for linkage and segregation. Only non-sib relatives undergo screening for greater efficiency of phenotyping. The research plan components are: a) phenotypic characterization of childhood OCD; b) linkage using affected-relative pairs to 4 candidate gene regions (SLC6A4-serotonin transporter, COMT, MAOA, DRD4) using 3 SNP biallelic markers and 4 flanking microsatellite markers; c) complex segregation analysis to obtain the mode of transmission and major gene effect; d) family-based tests of linkage disequilibrium using the 4 candidate gene alleles and; e) tests of genetic heterogeneity with the tic-related OCD subtype. Based on results from initial analyses and developing collaborations with other research groups future research projects, such as a genome-wide screen of OCD, are considered.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH066284-05
Application #
7117639
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Desmond, Nancy L
Project Start
2002-09-20
Project End
2007-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
5
Fiscal Year
2006
Total Cost
$176,936
Indirect Cost
Name
Johns Hopkins University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Bienvenu, O J; Samuels, J F; Wuyek, L A et al. (2012) Is obsessive-compulsive disorder an anxiety disorder, and what, if any, are spectrum conditions? A family study perspective. Psychol Med 42:1-13
Voyiaziakis, E; Evgrafov, O; Li, D et al. (2011) Association of SLC6A4 variants with obsessive-compulsive disorder in a large multicenter US family study. Mol Psychiatry 16:108-20
Wang, Y; Samuels, J F; Chang, Y C et al. (2009) Gender differences in genetic linkage and association on 11p15 in obsessive-compulsive disorder families. Am J Med Genet B Neuropsychiatr Genet 150B:33-40
Bienvenu, O J; Wang, Y; Shugart, Y Y et al. (2009) Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study. Am J Med Genet B Neuropsychiatr Genet 150B:710-20
Pinto, Anthony; Greenberg, Benjamin D; Grados, Marco A et al. (2008) Further development of YBOCS dimensions in the OCD Collaborative Genetics study: symptoms vs. categories. Psychiatry Res 160:83-93
Wilcox, Holly C; Grados, Marco; Samuels, Jack et al. (2008) The association between parental bonding and obsessive compulsive disorder in offspring at high familial risk. J Affect Disord 111:31-9
Grados, Marco A; Mathews, Carol A; Tourette Syndrome Association International Consortium for Genetics (2008) Latent class analysis of gilles de la tourette syndrome using comorbidities: clinical and genetic implications. Biol Psychiatry 64:219-25
Grados, Marco A; Vasa, Roma A; Riddle, Mark A et al. (2008) New onset obsessive-compulsive symptoms in children and adolescents with severe traumatic brain injury. Depress Anxiety 25:398-407
Grados, Marco; Riddle, Mark A (2008) Do all obsessive-compulsive disorder subtypes respond to medication? Int Rev Psychiatry 20:189-93
Wellen, David; Samuels, Jack; Bienvenu, O Joseph et al. (2007) Utility of the Leyton Obsessional Inventory to distinguish OCD and OCPD. Depress Anxiety 24:301-6

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