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

Authors:
Lauren M McGrath Dongmei Yu Christian Marshall Lea K Davis Bhooma Thiruvahindrapuram Bingbin Li Carolina Cappi Gloria Gerber Aaron Wolf Frederick A Schroeder Lisa Osiecki Colm O'Dushlaine Andrew Kirby Cornelia Illmann Stephen Haddad Patience Gallagher Jesen A Fagerness Cathy L Barr Laura Bellodi Fortu Benarroch O Joseph Bienvenu Donald W Black Michael H Bloch Ruth D Bruun Cathy L Budman Beatriz Camarena Danielle C Cath Maria C Cavallini Sylvain Chouinard Vladimir Coric Bernadette Cullen Richard Delorme Damiaan Denys Eske M Derks Yves Dion Maria C Rosário Valsama Eapen Patrick Evans Peter Falkai Thomas V Fernandez Helena Garrido Daniel Geller Hans J Grabe Marco A Grados Benjamin D Greenberg Varda Gross-Tsur Edna Grünblatt Gary A Heiman Sian M J Hemmings Luis D Herrera Ana G Hounie Joseph Jankovic James L Kennedy Robert A King Roger Kurlan Nuria Lanzagorta Marion Leboyer James F Leckman Leonhard Lennertz Christine Lochner Thomas L Lowe Gholson J Lyon Fabio Macciardi Wolfgang Maier James T McCracken William McMahon Dennis L Murphy Allan L Naarden Benjamin M Neale Erika Nurmi Andrew J Pakstis Michele T Pato Carlos N Pato John Piacentini Christopher Pittenger Yehuda Pollak Victor I Reus Margaret A Richter Mark Riddle Mary M Robertson David Rosenberg Guy A Rouleau Stephan Ruhrmann Aline S Sampaio Jack Samuels Paul Sandor Brooke Sheppard Harvey S Singer Jan H Smit Dan J Stein Jay A Tischfield Homero Vallada Jeremy Veenstra-VanderWeele Susanne Walitza Ying Wang Jens R Wendland Yin Yao Shugart Euripedes C Miguel Humberto Nicolini Ben A Oostra Rainald Moessner Michael Wagner Andres Ruiz-Linares Peter Heutink Gerald Nestadt Nelson Freimer Tracey Petryshen Danielle Posthuma Michael A Jenike Nancy J Cox Gregory L Hanna Helena Brentani Stephen W Scherer Paul D Arnold S Evelyn Stewart Carol A Mathews James A Knowles Edwin H Cook David L Pauls Kai Wang Jeremiah M Scharf

J Am Acad Child Adolesc Psychiatry 2014 Aug 24;53(8):910-9. Epub 2014 Jun 24.

Massachusetts General Hospital, Boston; Brigham and Womens Hospital, Boston; Harvard-MIT Broad Institute, Boston. Electronic address:

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.

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Source
http://dx.doi.org/10.1016/j.jaac.2014.04.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4218748PMC
August 2014
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