[Show abstract][Hide abstract] ABSTRACT: 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 × 10(-6) and P=3.44 × 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 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 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.Molecular Psychiatry advance online publication, 14 August 2012; doi:10.1038/mp.2012.85.
Full-text · Article · Aug 2012 · Molecular Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Obsessive compulsive disorder (OCD) has a complex etiology that encompasses both genetic and environmental factors. However, to date, despite the identification of several promising candidate genes and linkage regions, the genetic causes of OCD are largely unknown. The objective of this study was to conduct linkage studies of childhood-onset OCD, which is thought to have the strongest genetic etiology, in several OCD-affected families from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The authors used parametric and non-parametric approaches to conduct genome-wide linkage analyses using 5,786 single nucleotide repeat polymorphisms (SNPs) in three CVCR families with multiple childhood-onset OCD-affected individuals. We identified areas of suggestive linkage (LOD score ≥ 2) on chromosomes 1p21, 15q14, 16q24, and 17p12. The strongest evidence for linkage was on chromosome 15q14 (LOD = 3.13), identified using parametric linkage analysis with a recessive model, and overlapping a region identified in a prior linkage study using a Caucasian population. Each CVCR family had a haplotype that co-segregated with OCD across a ~7 Mbp interval within this region, which contains 18 identified brain expressed genes, several of which are potentially relevant to OCD. Exonic sequencing of the strongest candidate gene in this region, the ryanodine receptor 3 (RYR3), identified several genetic variants of potential interest, although none co-segregated with OCD in all three families. These findings provide evidence that chromosome 15q14 is linked to OCD in families from the CVCR, and supports previous findings to suggest that this region may contain one or more OCD susceptibility loci.
[Show abstract][Hide abstract] ABSTRACT: It has been suggested that attention-deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD), both neurodevelopmental disorders with onset in childhood, are highly comorbid, but previous studies examining ADHD and OCD comorbidity have been quite variable, partly because of inconsistency in excluding individuals with tic disorders. Similarly, ADHD has been postulated to be associated with hoarding although this potential relationship is largely methodologically unexplored. This study aimed to examine the prevalence of ADHD among individuals with childhood-onset OCD but without comorbid tic disorders, as well as to examine the relationship between clinically significant hoarding behaviors (hoarding) and ADHD.
ADHD prevalence rates and the relationship between ADHD and hoarding were examined in 155 OCD-affected individuals (114 probands and 41 relatives, age range 4-82 years) recruited for genetic studies and compared to pooled prevalence rates derived from previously published studies.
In total, 11.8% met criteria for definite ADHD, whereas an additional 8.6% had probable or definite ADHD (total=20.4%). In total, 41.9% of participants with ADHD also had hoarding compared to 29.2% of participants without ADHD. Hoarding was the only demographic or clinical variable independently associated with ADHD (odds ratio=9.54, P<0.0001).
ADHD rates were elevated in this sample of individuals with childhood-onset OCD compared to the general population rate of ADHD, and there was a strong association between ADHD and clinically significant hoarding behavior. This association is consistent with recent studies suggesting that individuals with hoarding may exhibit substantial executive functioning impairments and/or abnormalities, including attentional problems.
Full-text · Article · Jul 2010 · Depression and Anxiety