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. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p =.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p =.08 in the current study, p =.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.
|Titolo:||Copy number variation in obsessive-compulsive disorder and tourette syndrome : a cross-disorder study|
|Parole Chiave:||16p13.11; copy number variation; genetics; obsessive-compulsive disorder; Tourette syndrome; Adolescent; Diagnostic and Statistical Manual of Mental Disorders; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Male; Obsessive-Compulsive Disorder; Polymorphism, Single Nucleotide; Tourette Syndrome; DNA Copy Number Variations; Psychiatry and Mental Health; Developmental and Educational Psychology|
|Settore Scientifico Disciplinare:||Settore MED/03 - Genetica Medica|
Settore MED/25 - Psichiatria
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||10.1016/j.jaac.2014.04.022|
|Appare nelle tipologie:||01 - Articolo su periodico|