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Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study

2014; Elsevier BV; Volume: 53; Issue: 8 Linguagem: Inglês

10.1016/j.jaac.2014.04.022

1527-5418

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

Autism Spectrum Disorder Research

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 ( 500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. 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. 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%). 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.