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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-GGG-D (62))
Program Officer
Bender, Patrick
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Medicine
Los Angeles
United States
Zip Code
Abdulkadir, Mohamed; Mathews, Carol A; Scharf, Jeremiah M et al. (2018) Polygenic Risk Scores Derived From a Tourette Syndrome Genome-wide Association Study Predict Presence of Tics in the Avon Longitudinal Study of Parents and Children Cohort. Biol Psychiatry :
Khramtsova, Ekaterina A; Heldman, Raphael; Derks, Eske M et al. (2018) Sex differences in the genetic architecture of obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet :
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
Chen, David; Bienvenu, O Joseph; Krasnow, Janice et al. (2017) Parental bonding and hoarding in obsessive-compulsive disorder. Compr Psychiatry 73:43-52
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
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
Stewart, S E; Mayerfeld, C; Arnold, P D et al. (2013) Meta-analysis of association between obsessive-compulsive disorder and the 3' region of neuronal glutamate transporter gene SLC1A1. Am J Med Genet B Neuropsychiatr Genet 162B:367-79
Nestadt, G; Wang, Y; Grados, M A et al. (2012) Homeobox genes in obsessive-compulsive disorder. Am J Med Genet B Neuropsychiatr Genet 159B:53-60

Showing the most recent 10 out of 13 publications