Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.

Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study.

Objective: Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date.

Method: The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls.

Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture.

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.

Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses.

Rare sequence variants may be important in understanding the biology of common diseases, but clearly establishing their association with disease is often difficult. Association studies of such variants are becoming increasingly common as large-scale sequence analysis of candidate genes has become feasible. A recent report suggested SLITRK1 (Slit and Trk-like 1) as a candidate gene for Tourette Syndrome (TS).