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

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 BenarrochO. 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


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.

Original languageAmerican English
Pages (from-to)910-919
Number of pages10
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number8
StatePublished - Aug 2014
Externally publishedYes


  • 16p13.11
  • Tourette syndrome
  • copy number variation
  • genetics
  • obsessive-compulsive disorder


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