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

McGrath, Lauren M., Yu, Dongmei, Marshall, Christian, Davis, Lea K., Thiruvahindrapuram, Bhooma, Li, Bingbin, Cappi, Carolina, Geber, Gloria, Wolf, Aaron, Schroeder, Frederick A., Osiecki, Lisa, O'Dushlaine, Colm, Kirby, Andrew, Illman, Cornelia, Haddad, Stephen, Gallagher, Patience, Fagerness, Jesen A., Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Bienvenu, O. Joseph, Black, Donald W., Bloch, Michael H. , Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz, Cath, Danielle C., Cavallini, Maria C,, Chouinard, Sylvain, Coric , Vladimir, Cullen, Bernadette, Delomre, Richard, Denys, Damiaan, Derks, Eske M., Dion, Yves, Rosario, Maria C., Eapen, Valsama, Evans, Patrick, Falkai, Peter, Fernanadez , Thomas, Garrido, Helena, Geller, Daniel, Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Grunblatt, Edna, Heiman , Gary A, Hemmings, Sian M.J., Herrera, Luis D., Hounie, Ana G., Jankovic, Joseph, Kennedy, James L., King, Robert A., Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F., Lennertz, Leonhard, Lochner , Christine, Lowe, Thomas L., Lyon, Gholson J,, Maccaiardi, Fabio, Maier, Wolfgang, McCracken, James T., McMahon, William, Murphy, Dennis L., Naarden, Allan L., Neale, Benjamin M., Nurmi, Erika, Pakstis , Andrew J,, Pato, Michele T., Pato, Carlos N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Reus, Victor I., Richter, Maragret A., Riddle, Mark, Robertson, Mary M., Rosenberg, David , Rouleau, Guy A., Ruhrmann, Stephan, Sampaio, Aline S., Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S., Smit, Jan H., Stein , Dan J., Tishfield, Jay A., Vallada, Homero, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Wang, Ying, Wendland, Jens R., Shugart , Yin Yao, Miguel, Euripedes C., Nicolini, Humberto, Oostra, Ben A., Moessner, Rainald, Wagner, Michael, Ruiz-Linares, Andres, Heutink, Peter, Nestadt, Gerald, Freimer, Nelson, Petryshen, Tracey, Posthuma, Danielle, Jenike, Michael A., Cox, Nancy J., Hanna, Gregory L., Brentani, Helena, Schrerer , Stephen W., Arnold, Paul D., Stewart, S. Evelyn, Matthews, Carol A., Knowles, James A., Cook, Edwin H., Pauls, David L., Wang, Kai, Scharf, Jeremiah M. (April 2014) Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study. Journal of American Academy of Child & Adolescent Psychiatry, 53 (8). pp. 910-9. (In Press)

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DOI: 10.1016/j.jaac.2014.04.022


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 (>500kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses utilized a cross-disorder design for 2,699 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 patient deletions: 0 control deletions, p=0.08 in current study, p=0.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support to 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 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.

Item Type: Paper
Subjects: diseases & disorders
diseases & disorders > mental disorders > impulse control disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > copy number variants
CSHL Authors:
Communities: CSHL labs > Lyon lab
Depositing User: Andrea Potopsingh
Date: 26 April 2014
Date Deposited: 28 Jul 2014 15:18
Last Modified: 31 Jan 2017 20:32
PMCID: PMC4218748
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