Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Author Davis, Lea K. Google Scholar
Yu, Dongmei Google Scholar
Keenan, Clare L. Google Scholar
Gamazon, Eric R. Google Scholar
Konkashbaev, Anuar I. Google Scholar
Derks, Eske M. Google Scholar
Neale, Benjamin M. Google Scholar
Yang, Jian Google Scholar
Lee, S. Hong Google Scholar
Evans, Patrick Google Scholar
Barr, Cathy L. Google Scholar
Bellodi, Laura Google Scholar
Benarroch, Fortu Google Scholar
Berrio, Gabriel Bedoya Google Scholar
Bienvenu, Oscar J. Google Scholar
Bloch, Michael H. Google Scholar
Blom, Rianne M. Google Scholar
Bruun, Ruth D. Google Scholar
Budman, Cathy L. Google Scholar
Camarena, Beatriz Google Scholar
Campbell, Desmond Google Scholar
Cappi, Carolina Google Scholar
Silgado, Julio C. Cardona Google Scholar
Cath, Danielle C. Google Scholar
Cavallini, Maria C. Google Scholar
Chavira, Denise A. Google Scholar
Chouinard, Sylvain Google Scholar
Conti, David V. Google Scholar
Cook, Edwin H. Google Scholar
Coric, Vladimir Google Scholar
Cullen, Bernadette A. Google Scholar
Deforce, Dieter Google Scholar
Delorme, Richard Google Scholar
Dion, Yves Google Scholar
Edlund, Christopher K. Google Scholar
Egberts, Karin Google Scholar
Falkai, Peter Google Scholar
Fernandez, Thomas V. Google Scholar
Gallagher, Patience J. Google Scholar
Garrido, Helena Google Scholar
Geller, Daniel Google Scholar
Girard, Simon L. Google Scholar
Grabe, Hans J. Google Scholar
Grados, Marco A. Google Scholar
Greenberg, Benjamin D. Google Scholar
Gross-Tsur, Varda Google Scholar
Haddad, Stephen Google Scholar
Heiman, Gary A. Google Scholar
Hemmings, Sian M. J. Google Scholar
Hounie, Ana G. Google Scholar
Illmann, Cornelia Google Scholar
Jankovic, Joseph Google Scholar
Jenike, Michael A. Google Scholar
Kennedy, James L. Google Scholar
King, Robert A. Google Scholar
Kremeyer, Barbara Google Scholar
Kurlan, Roger Google Scholar
Lanzagorta, Nuria Google Scholar
Leboyer, Marion Google Scholar
Leckman, James F. Google Scholar
Lennertz, Leonhard Google Scholar
Liu, Chunyu Google Scholar
Lochner, Christine Google Scholar
Lowe, Thomas L. Google Scholar
Macciardi, Fabio Google Scholar
McCracken, James T. Google Scholar
McGrath, Lauren M. Google Scholar
Restrepo, Sandra C. Mesa Google Scholar
Moessner, Rainald Google Scholar
Morgan, Jubel Google Scholar
Muller, Heike Google Scholar
Murphy, Dennis L. Google Scholar
Naarden, Allan L. Google Scholar
Ochoa, William Cornejo Google Scholar
Ophoff, Roel A. Google Scholar
Osiecki, Lisa Google Scholar
Pakstis, Andrew J. Google Scholar
Pato, Michele T. Google Scholar
Pato, Carlos N. Google Scholar
Piacentini, John Google Scholar
Pittenger, Christopher Google Scholar
Pollak, Yehuda Google Scholar
Rauch, Scott L. Google Scholar
Renner, Tobias J. Google Scholar
Reus, Victor I. Google Scholar
Richter, Margaret A. Google Scholar
Riddle, Mark A. Google Scholar
Robertson, Mary M. Google Scholar
Romero, Roxana Google Scholar
Rosario, Maria C. Autor UNIFESP Google Scholar
Rosenberg, David Google Scholar
Rouleau, Guy A. Google Scholar
Ruhrmann, Stephan Google Scholar
Ruiz-Linares, Andres Google Scholar
Sampaio, Aline S. Google Scholar
Samuels, Jack Google Scholar
Sandor, Paul Google Scholar
Sheppard, Brooke Google Scholar
Singer, Harvey S. Google Scholar
Smit, Jan H. Google Scholar
Stein, Dan J. Google Scholar
Strengman, E. Google Scholar
Tischfield, Jay A. Google Scholar
Duarte, Ana V. Valencia Google Scholar
Vallada, Homero Google Scholar
Van Nieuwerburgh, Filip Google Scholar
Veenstra-VanderWeele, Jeremy Google Scholar
Walitza, Susanne Google Scholar
Wang, Ying Google Scholar
Wendland, Jens R. Google Scholar
Westenberg, Herman G. M. Google Scholar
Shugart, Yin Yao Google Scholar
Miguel, Euripedes C. Google Scholar
McMahon, William Google Scholar
Wagner, Michael Google Scholar
Nicolini, Humberto Google Scholar
Posthuma, Danielle Google Scholar
Hanna, Gregory L. Google Scholar
Heutink, Peter Google Scholar
Denys, Damiaan Google Scholar
Arnold, Paul D. Google Scholar
Oostra, Ben A. Google Scholar
Nestadt, Gerald Google Scholar
Freimer, Nelson B. Google Scholar
Pauls, David L. Google Scholar
Wray, Naomi R. Google Scholar
Stewart, S. Evelyn Google Scholar
Mathews, Carol A. Google Scholar
Knowles, James A. Google Scholar
Cox, Nancy J. Google Scholar
Scharf, Jeremiah M. Google Scholar
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Abstract The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. in addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. in addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. the results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
Language English
Sponsor Judah Foundation
NIH
Tourette Syndrome Association International Consortium for Genetics (TSAICG)
New Jersey Center for Tourette Syndrome and Associated Disorders
NIMH
Obsessive Compulsive Foundation
Ontario Mental Health Foundation
Tourette Syndrome Association
American Academy of Child and Adolescent Psychiatry (AACAP)
Anxiety Disorders Association of America (ADAA)
University of British Columbia
Michael Smith Foundation
American Recovery and Re-investment Act (ARRA)
Australian Research Council
Australian National Health and Medical Research Council
German Research Foundation
NIH Genes, Environment and Health Initiative [GEI]
Gene Environment Association Studies (GENEVA) under GEI
NIH GEI
National Institute on Alcohol Abuse and Alcoholism
National Institute on Drug Abuse
Grant number NIH: NS40024
NIH: NS16648
NIH: MH079489
NIH: MH073250
NIH: NS037484
NIH: 1R01MH079487-01A1
NIH: K20 MH01065
NIH: R01 MH58376
NIH: MH085057
NIH: MH079494
NIH: HHSN268200782096C
NIMH: R01MH092293
American Recovery and Re-investment Act (ARRA): NS40024-07S1
American Recovery and Re-investment Act (ARRA): NS16648-29S1
Australian Research Council: FT0991360
Australian Research Council: DE130100614
Australian National Health and Medical Research Council: 1047956
Australian National Health and Medical Research Council: 1052684
German Research Foundation: DFG GR 1912/1-1
NIH Genes, Environment and Health Initiative [GEI]: U01 HG004422
NIH GEI: U01HG004438
: R01 MH090937
: P50MH094267
Date 2013-10-01
Published in Plos Genetics. San Francisco: Public Library Science, v. 9, n. 10, 14 p., 2013.
ISSN 1553-7404 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 14
Origin http://dx.doi.org/10.1371/journal.pgen.1003864
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000330367200041
URI http://repositorio.unifesp.br/handle/11600/36782

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