Journal
MOLECULAR PSYCHIATRY
Volume 18, Issue 7, Pages 788-798Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2012.85
Keywords
DLGAP; genetic; genomic; GWAS; neurodevelopmental disorder; obsessive-compulsive disorder
Funding
- Judah Foundation
- NIH [MH079489, MH073250]
- American Recovery and Re-investment Act (ARRA) awards [NS40024-07S1, NS16648-29S1]
- American Academy of Child and Adolescent Psychiatry (AACAP)
- Anxiety Disorders Association of America (ADAA)
- University of British Columbia
- Michael Smith Foundation Clinical Research Scholar Award
- Tourette Syndrome Association
- American Academy of Neurology Foundation
- National Center for Research Resources [RR020278]
- NIH Genes, Environment and Health Initiative [GEI] [U01 HG004422]
- NIH GEI [U01HG004438]
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse
- NIH contract 'High throughput genotyping for studying the genetic contributions to human disease' [HHSN268200782096C]
- UK Medical Research Council
- National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG000932-02]
- MRC [G0701075, G0901254, MR/K01417X/1, G0802462] Funding Source: UKRI
- Alzheimers Research UK [ART-PPG2011A-14] Funding Source: researchfish
- Medical Research Council [G0901254, MR/J006742/1, MR/K01417X/1, G0802462, G0701075] Funding Source: researchfish
Ask authors/readers for more resources
Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469 410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P = 2.49 x 10(-6) and P = 3.44 x 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value = 3.84 x 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 x 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P < 0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P = 0.001) was observed within the top-ranked SNPs (P < 0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available