The OCD Collaborative Genetics Group proposes to conduct a genome-wide association study of early-onset obsessive-compulsive disorder (OCD). This group of six academic centers has collaborated over the past five years on an on-going genetic linkage study of OCD and has demonstrated ability to recruit and diagnose individuals with this disorder. In this proposal, the Collaboration will conduct psychiatric evaluations on 2,000 individuals with obsessive-compulsive disorder (OCD) and collect DNA from these individuals and both their parents. The genotyping and analyses will be performed in two stages. In the first stage 1,000 triads will be genotyped with a 550,000 single nucleotide polymorphisms (SNPs) panel at the Illumina laboratory. We will estimate the genetic effect sizes for all 550,000 SNPs, and then rank all SNPs based on their conditional power estimates. The 1,534 SNPs with the highest power rankings will be genotyped in the second stage (1,000 triads). The combined p-values from the two stages (which will have to be adjusted for only 1,534 comparisons, but not for 550,000) that are less than 5%/1534 (Bonferroni correction) will be considered genome-wide significant. The indirect association approach proposed will be followed up using more direct association techniques (gene based), innovative gene-gene interaction analyses (gene cluster based), and additional molecular and functional approaches. The results of these analyses will guide future molecular strategies to identify genes involved in the pathogenesis of OCD. The clinical and genotype data from the sample will be publicly available for OCD genetics research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH079494-05
Application #
8117686
Study Section
Special Emphasis Panel (ZRG1-GGG-D (62))
Program Officer
Senthil, Geetha
Project Start
2007-09-29
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2011
Total Cost
$107,210
Indirect Cost
Name
University of Southern California
Department
Psychiatry
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Samuels, Jack; Bienvenu, O Joseph; Krasnow, Janice et al. (2017) An investigation of doubt in obsessive-compulsive disorder. Compr Psychiatry 75:117-124
Chen, David; Bienvenu, O Joseph; Krasnow, Janice et al. (2017) Parental bonding and hoarding in obsessive-compulsive disorder. Compr Psychiatry 73:43-52
Guo, W; Samuels, J F; Wang, Y et al. (2017) Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD. Eur Neuropsychopharmacol 27:657-666
Qin, H; Samuels, J F; Wang, Y et al. (2016) Whole-genome association analysis of treatment response in obsessive-compulsive disorder. Mol Psychiatry 21:270-6
Riddle, Mark A; Maher, Brion S; Wang, Ying et al. (2016) OBSESSIVE-COMPULSIVE PERSONALITY DISORDER: EVIDENCE FOR TWO DIMENSIONS. Depress Anxiety 33:128-35
Mattheisen, M; Samuels, J F; Wang, Y et al. (2015) Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry 20:337-44
Yu, Dongmei; Mathews, Carol A; Scharf, Jeremiah M et al. (2015) Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD. Am J Psychiatry 172:82-93
Davis, Lea K; Yu, Dongmei; Keenan, Clare L et al. (2013) Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genet 9:e1003864
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