Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/38616
Title: Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD
Authors: Yu, Dongmei
Mathews, Carol A.
Scharf, Jeremiah M.
Neale, Benjamin M.
Davis, Lea K.
Gamazon, Eric R.
Derks, Eske M.
Evans, Patrick
Edlund, Christopher K.
Crane, Jacquelyn
Osiecki, Lisa
Gallagher, Patience
Gerber, Gloria
Haddad, Stephen
Illmann, Cornelia
McGrath, Lauren M.
Mayerfeld, Catherine
Arepalli, Sampath
Barlassina, Cristina
Barr, Cathy L.
Bellodi, Laura
Benarroch, Fortu
Berrio, Gabriel Bedoya
Bienvenu, O. Joseph
Black, Donald W.
Bloch, Michael H.
Brentani, Helena
Bruun, Ruth D.
Budman, Cathy L.
Camarena, Beatriz
Campbell, Desmond D.
Cappi, Carolina
Silgado, Julio C. Cardona
Cavallini, Maria C.
Chavira, Denise A.
Chouinard, Sylvain
Cook, Edwin H.
Cookson, M. R.
Coric, Vladimir
Cullen, Bernadette
Cusi, Daniete
Delorme, Richard
Denys, Damiaan
Dion, Yves
Eapen, Valsama
Egberts, Karin
Falkai, Peter
Fernandez, Thomas
Fournier, Eduardo
Garrido, Helena
Geller, Daniel
Gilbert, Donald L.
Girard, Simon L.
Grabe, Hans J.
Grados, Marco A.
Greenberg, Benjamin D.
Gross-Tsur, Varda
Gruenblatt, Edna
Hardy, John
Heiman, Gary A.
Hemmings, Sian M. J.
Herrera, Luis D.
Hezel, Dianne M.
Hoekstra, Pieter J.
Jankovic, Joseph
Kennedy, James L.
King, Robert A.
Konkashbaev, Anuar I.
Kremeyer, Barbara
Kurlan, Roger
Lanzagorta, Nuria
Leboyer, Marion
Leckman, James F.
Lennertz, Leonhard
Liu, Chunyu
Lochner, Christine
Lowe, Thomas L.
Lupoli, Sara
Macciardi, Fabio
Maier, Wolfgang
Manunta, Paolo
Marconi, Maurizio
McCracken, James T.
Restrepo, Sandra C. Mesa
Moessner, Rainald
Moorjani, Priya
Morgan, Jubel
Muller, Heike
Murphy, Dennis L.
Naarden, Allan L.
Nurmi, Erika
Ochoa, William Cornejo
Ophoff, Roel A.
Pakstis, Andrew J.
Pato, Michele T.
Pato, Carlo N.
Piacentini, John
Pittenger, Christopher
Pollak, Yehuda
Rauch, Scott L.
Renner, Tobias
Reus, Victor I.
Richter, Margaret A.
Riddle, Mark A.
Robertson, Mary M.
Romero, Roxana
Rosario, Maria C.
Rosenberg, David
Ruhrmann, Stephan
Sabatti, Chiara
Salvi, Erika
Sampaio, Aline S.
Samuels, Jack
Sandor, Paul
Service, Susan K.
Sheppard, Brooke
Singer, Harvey S.
Smit, Jan H.
Stein, Dan J.
Strengman, Eric
Tischfield, Jay A.
Turiel, Maurizio
Duarte, Ana V. Valencia
Vallada, Homero
Veenstra-VanderWeele, Jeremy
Walitza, Susanne
Wang, Ying
Weale, Mike
Weiss, Robert
Wendland, Jens R.
Westenberg, Herman G. M.
Shugart, Yin Yao
Hounie, Ana G.
Miguel, Euripedes C.
Nicolini, Humberto
Wagner, Michael
Ruiz-Linares, Andres
Cath, Danielle C.
McMahon, William
Posthuma, Danielle
Oostra, Ben A.
Nestadt, Gerald
Routeau, Guy A.
Purcell, Shaun
Jenike, Michael A.
Heutink, Peter
Hanna, Gregory L.
Conti, David V.
Arnold, Paul D.
Freimer, Nelson B.
Stewart, Evelyn
Knowles, James A.
Cox, Nancy J.
Pauls, David L.
Harvard Univ
Broad Inst Harvard & MIT
Univ Calif San Francisco
Massachusetts Gen Hosp
Brigham & Womens Hosp
Univ Chicago
Univ Amsterdam
Univ So Calif
NIA
Filarete Fdn
Univ Milan
Univ Hlth Network
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Hadassah Hebrew Univ
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Johns Hopkins Univ
Univ Iowa
Yale Univ
Universidade de São Paulo (USP)
North Shore Long Isl Jewish Med Ctr
North Shore Long Isl Jewish Hlth Syst
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Inst Nacl Psiquiatria Ramon de la Fuente Muniz
UCL
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South West Sydney Local Hlth Dist AUCS
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Clin Herrera Amighetti
Cincinnati Childrens Hosp Med Ctr
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Univ Zurich
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Univ Stellenbosch
Univ Groningen
Baylor Coll Med
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Univ Toronto
Overlook Hosp
Carracci Med Grp
Inst Mondor Rech Biomed
Univ Bonn
Univ Cape Town
Univ Calif Irvine
IRCCS San Raffaele Sci Inst
Fdn IRCCS CaGranda Osped Maggiore Policlin
Columbia Univ
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NIMH Intramural Res Program
Med City Dallas Hosp
Univ Med Ctr
Partners Psychiat
McLean Hosp
Sunnybrook Hlth Sci Ctr
St Georges Hosp & Med Sch
Universidade Federal de São Paulo (UNIFESP)
Wayne State Univ
Detroit Med Ctr
Univ Cologne
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Youthdate Treatment Ctr
Vrije Univ Amsterdam Med Ctr
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Mt Sinai Med Ctr
German Ctr Neurodegenerat Dis
Univ Michigan
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Issue Date: 1-Jan-2015
Publisher: Amer Psychiatric Publishing, Inc
Citation: American Journal of Psychiatry. Arlington: Amer Psychiatric Publishing, Inc, v. 172, n. 1, p. 82-93, 2015.
Abstract: Objective: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. the authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.Method: the authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.Results: Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders Polygenic score analyses identified a significant polygenic component for OCD (p=2x10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. in contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).Conclusions: Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring burette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.
URI: http://repositorio.unifesp.br/handle/11600/38616
ISSN: 0002-953X
Other Identifiers: http://dx.doi.org/10.1176/appi.ajp.2014.13101306
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