Yu, Dongmei ORCID: 0000-0001-7901-4365, 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 ORCID: 0000-0001-7407-2697, Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Berrio, Gabriel Bedoya, Bienvenu, O. Joseph, Black, Donald W., Bloch, Michael H., Brentani, Helena ORCID: 0000-0001-5192-4682, Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz ORCID: 0000-0001-7737-501X, Campbell, Desmond D., Cappi, Carolina ORCID: 0000-0001-6661-3756, 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 ORCID: 0000-0002-5614-3663, Denys, Damiaan, Dion, Yves, Eapen, Valsama, Egberts, Karin, Falkai, Peter ORCID: 0000-0003-2873-8667, Fernandez, Thomas, Fournier, Eduardo, Garrido, Helena, Geller, Daniel, Gilbert, Donald L. ORCID: 0000-0002-9245-6878, Girard, Simon L., Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Gruenblatt, Edna, Hardy, John ORCID: 0000-0002-3122-0423, 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 ORCID: 0000-0001-6769-6813, Leboyer, Marion, Leckman, James F., Lennertz, Leonhard, Liu, Chunyu ORCID: 0000-0002-5986-4415, Lochner, Christine, Lowe, Thomas L., Lupoli, Sara, Macciardi, Fabio ORCID: 0000-0003-0537-4266, Maier, Wolfgang, Manunta, Paolo ORCID: 0000-0003-3976-9696, 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 ORCID: 0000-0003-4893-8957, Ochoa, William Cornejo ORCID: 0000-0002-9065-8185, Ophoff, Roel A., Pakstis, Andrew J., Pato, Michele T., Pato, Carlo N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda ORCID: 0000-0002-1293-499X, 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 ORCID: 0000-0002-6022-2364, Sabatti, Chiara, Salvi, Erika ORCID: 0000-0002-2724-2291, Sampaio, Aline S., Samuels, Jack, Sandor, Paul ORCID: 0000-0003-2397-0758, 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 ORCID: 0000-0001-5123-8295, Veenstra-VanderWeele, Jeremy ORCID: 0000-0002-6349-1076, Walitza, Susanne ORCID: 0000-0002-8161-8683, Wang, Ying, Weale, Mike, Weiss, Robert, Wendland, Jens R., Westenberg, Herman G. M., Shugart, Yin Yao, Hounie, Ana G., Miguel, Euripedes C., Nicolini, Humberto ORCID: 0000-0003-2494-0067, Wagner, Michael ORCID: 0000-0003-2589-6440, Ruiz-Linares, Andres, Cath, Danielle C., McMahon, William, Posthuma, Danielle ORCID: 0000-0001-7582-2365, Oostra, Ben A., Nestadt, Gerald, Routeau, Guy A., Purcell, Shaun, Jenike, Michael A., Heutink, Peter ORCID: 0000-0001-5218-1737, Hanna, Gregory L., Conti, David V., Arnold, Paul D., Freimer, Nelson B., Stewart, Evelyn, Knowles, James A., Cox, Nancy J. and Pauls, David L. (2015). Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette's Syndrome and OCD. Am. J. Psychiat., 172 (1). S. 82 - 94. ARLINGTON: AMER PSYCHIATRIC PUBLISHING, INC. ISSN 1535-7228

Full text not available from this repository.

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Yu, DongmeiUNSPECIFIEDorcid.org/0000-0001-7901-4365UNSPECIFIED
Mathews, Carol A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scharf, Jeremiah M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neale, Benjamin M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davis, Lea K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gamazon, Eric R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Derks, Eske M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edlund, Christopher K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Crane, JacquelynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osiecki, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallagher, PatienceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerber, GloriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haddad, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Illmann, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGrath, Lauren M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayerfeld, CatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arepalli, SampathUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barlassina, CristinaUNSPECIFIEDorcid.org/0000-0001-7407-2697UNSPECIFIED
Barr, Cathy L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bellodi, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benarroch, FortuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berrio, Gabriel BedoyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bienvenu, O. JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Black, Donald W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloch, Michael H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brentani, HelenaUNSPECIFIEDorcid.org/0000-0001-5192-4682UNSPECIFIED
Bruun, Ruth D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Budman, Cathy L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Camarena, BeatrizUNSPECIFIEDorcid.org/0000-0001-7737-501XUNSPECIFIED
Campbell, Desmond D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cappi, CarolinaUNSPECIFIEDorcid.org/0000-0001-6661-3756UNSPECIFIED
Silgado, Julio C. CardonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cavallini, Maria C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chavira, Denise A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chouinard, SylvainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cook, Edwin H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cookson, M. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coric, VladimirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cullen, BernadetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cusi, DanieteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delorme, RichardUNSPECIFIEDorcid.org/0000-0002-5614-3663UNSPECIFIED
Denys, DamiaanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dion, YvesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eapen, ValsamaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Egberts, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Falkai, PeterUNSPECIFIEDorcid.org/0000-0003-2873-8667UNSPECIFIED
Fernandez, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fournier, EduardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garrido, HelenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geller, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gilbert, Donald L.UNSPECIFIEDorcid.org/0000-0002-9245-6878UNSPECIFIED
Girard, Simon L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grabe, Hans J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grados, Marco A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greenberg, Benjamin D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gross-Tsur, VardaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruenblatt, EdnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hardy, JohnUNSPECIFIEDorcid.org/0000-0002-3122-0423UNSPECIFIED
Heiman, Gary A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hemmings, Sian M. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrera, Luis D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hezel, Dianne M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoekstra, Pieter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jankovic, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kennedy, James L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
King, Robert A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konkashbaev, Anuar I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kremeyer, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kurlan, RogerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lanzagorta, NuriaUNSPECIFIEDorcid.org/0000-0001-6769-6813UNSPECIFIED
Leboyer, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leckman, James F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lennertz, LeonhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, ChunyuUNSPECIFIEDorcid.org/0000-0002-5986-4415UNSPECIFIED
Lochner, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lowe, Thomas L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lupoli, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Macciardi, FabioUNSPECIFIEDorcid.org/0000-0003-0537-4266UNSPECIFIED
Maier, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manunta, PaoloUNSPECIFIEDorcid.org/0000-0003-3976-9696UNSPECIFIED
Marconi, MaurizioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McCracken, James T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Restrepo, Sandra C. MesaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moessner, RainaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moorjani, PriyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgan, JubelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muller, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murphy, Dennis L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Naarden, Allan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nurmi, ErikaUNSPECIFIEDorcid.org/0000-0003-4893-8957UNSPECIFIED
Ochoa, William CornejoUNSPECIFIEDorcid.org/0000-0002-9065-8185UNSPECIFIED
Ophoff, Roel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pakstis, Andrew J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pato, Michele T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pato, Carlo N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piacentini, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pittenger, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pollak, YehudaUNSPECIFIEDorcid.org/0000-0002-1293-499XUNSPECIFIED
Rauch, Scott L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Renner, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reus, Victor I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richter, Margaret A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riddle, Mark A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robertson, Mary M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romero, RoxanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosario, Maria C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenberg, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruhrmann, StephanUNSPECIFIEDorcid.org/0000-0002-6022-2364UNSPECIFIED
Sabatti, ChiaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salvi, ErikaUNSPECIFIEDorcid.org/0000-0002-2724-2291UNSPECIFIED
Sampaio, Aline S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Samuels, JackUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sandor, PaulUNSPECIFIEDorcid.org/0000-0003-2397-0758UNSPECIFIED
Service, Susan K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sheppard, BrookeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singer, Harvey S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smit, Jan H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stein, Dan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strengman, EricUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tischfield, Jay A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Turiel, MaurizioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duarte, Ana V. ValenciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vallada, HomeroUNSPECIFIEDorcid.org/0000-0001-5123-8295UNSPECIFIED
Veenstra-VanderWeele, JeremyUNSPECIFIEDorcid.org/0000-0002-6349-1076UNSPECIFIED
Walitza, SusanneUNSPECIFIEDorcid.org/0000-0002-8161-8683UNSPECIFIED
Wang, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weale, MikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weiss, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wendland, Jens R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westenberg, Herman G. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shugart, Yin YaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hounie, Ana G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miguel, Euripedes C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nicolini, HumbertoUNSPECIFIEDorcid.org/0000-0003-2494-0067UNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Ruiz-Linares, AndresUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cath, Danielle C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McMahon, WilliamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Posthuma, DanielleUNSPECIFIEDorcid.org/0000-0001-7582-2365UNSPECIFIED
Oostra, Ben A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nestadt, GeraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Routeau, Guy A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Purcell, ShaunUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jenike, Michael A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heutink, PeterUNSPECIFIEDorcid.org/0000-0001-5218-1737UNSPECIFIED
Hanna, Gregory L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Conti, David V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, Paul D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freimer, Nelson B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stewart, EvelynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knowles, James A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cox, Nancy J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pauls, David L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-418326
DOI: 10.1176/appi.ajp.2014.13101306
Journal or Publication Title: Am. J. Psychiat.
Volume: 172
Number: 1
Page Range: S. 82 - 94
Date: 2015
Publisher: AMER PSYCHIATRIC PUBLISHING, INC
Place of Publication: ARLINGTON
ISSN: 1535-7228
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
OBSESSIVE-COMPULSIVE DISORDER; ASSOCIATION SCANS; GENERALIST GENES; VARIANTS; TICSMultiple languages
PsychiatryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41832

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