Davis, Lea K., Yu, Dongmei, Keenan, Clare L., Gamazon, Eric R., Konkashbaev, Anuar I., Derks, Eske M., Neale, Benjamin M., Yang, Jian ORCID: 0000-0003-2001-2474, Lee, S. Hong, Evans, Patrick, Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Berrio, Gabriel Bedoya, Bienvenu, Oscar J., Bloch, Michael H., Blom, Rianne M., Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz ORCID: 0000-0001-7737-501X, Campbell, Desmond ORCID: 0000-0003-1085-714X, Cappi, Carolina ORCID: 0000-0001-6661-3756, Silgado, Julio C. Cardona, Cath, Danielle C., Cavallini, Maria C., Chavira, Denise A., Chouinard, Sylvain, Conti, David V., Cook, Edwin H., Coric, Vladimir, Cullen, Bernadette A., Deforce, Dieter, Delorme, Richard ORCID: 0000-0002-5614-3663, Dion, Yves, Edlund, Christopher K., Egberts, Karin, Falkai, Peter ORCID: 0000-0003-2873-8667, Fernandez, Thomas V., Gallagher, Patience J., Garrido, Helena, Geller, Daniel, Girard, Simon L., Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Haddad, Stephen, Heiman, Gary A., Hemmings, Sian M. J., Hounie, Ana G., Illmann, Cornelia, Jankovic, Joseph, Jenike, Michael A., Kennedy, James L., King, Robert A., 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., Macciardi, Fabio ORCID: 0000-0003-0537-4266, McCracken, James T., McGrath, Lauren M., Restrepo, Sandra C. Mesa, Moessner, Rainald, Morgan, Jubel, Muller, Heike, Murphy, Dennis L., Naarden, Allan L., Ochoa, William Cornejo ORCID: 0000-0002-9065-8185, Ophoff, Roel A., Osiecki, Lisa, Pakstis, Andrew J., Pato, Michele T., Pato, Carlos N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda ORCID: 0000-0002-1293-499X, Rauch, Scott L., Renner, Tobias J., Reus, Victor I., Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Romero, Roxana, Rosario, Maria C., Rosenberg, David, Rouleau, Guy A., Ruhrmann, Stephan ORCID: 0000-0002-6022-2364, Ruiz-Linares, Andres, Sampaio, Aline S., Samuels, Jack ORCID: 0000-0002-6715-7905, Sandor, Paul ORCID: 0000-0003-2397-0758, Sheppard, Brooke, Singer, Harvey S., Smit, Jan H., Stein, Dan J., Strengman, E., Tischfield, Jay A., Duarte, Ana V. Valencia, Vallada, Homero ORCID: 0000-0001-5123-8295, Van Nieuwerburgh, Filip ORCID: 0000-0001-8815-5485, Veenstra-VanderWeele, Jeremy ORCID: 0000-0002-6349-1076, Walitza, Susanne ORCID: 0000-0002-8161-8683, Wang, Ying, Wendland, Jens R., Westenberg, Herman G. M., Shugart, Yin Yao, Miguel, Euripedes C., McMahon, William, Wagner, Michael ORCID: 0000-0003-2589-6440, Nicolini, Humberto ORCID: 0000-0003-2494-0067, Posthuma, Danielle ORCID: 0000-0001-7582-2365, Hanna, Gregory L., Heutink, Peter ORCID: 0000-0001-5218-1737, Denys, Damiaan, Arnold, Paul D., Oostra, Ben A., Nestadt, Gerald, Freimer, Nelson B., Pauls, David L., Wray, Naomi R., Stewart, S. Evelyn ORCID: 0000-0002-0994-6383, Mathews, Carol A., Knowles, James A., Cox, Nancy J. and Scharf, Jeremiah M. (2013). Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture. PLoS Genet., 9 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7404

Full text not available from this repository.

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Davis, Lea K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yu, DongmeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keenan, Clare L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gamazon, Eric R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Konkashbaev, Anuar I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Derks, Eske M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neale, Benjamin M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, JianUNSPECIFIEDorcid.org/0000-0003-2001-2474UNSPECIFIED
Lee, S. HongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evans, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barr, Cathy L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bellodi, LauraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benarroch, FortuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berrio, Gabriel BedoyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bienvenu, Oscar J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bloch, Michael H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blom, Rianne M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruun, Ruth D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Budman, Cathy L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Camarena, BeatrizUNSPECIFIEDorcid.org/0000-0001-7737-501XUNSPECIFIED
Campbell, DesmondUNSPECIFIEDorcid.org/0000-0003-1085-714XUNSPECIFIED
Cappi, CarolinaUNSPECIFIEDorcid.org/0000-0001-6661-3756UNSPECIFIED
Silgado, Julio C. CardonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cath, Danielle C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cavallini, Maria C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chavira, Denise A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chouinard, SylvainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Conti, David V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cook, Edwin H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coric, VladimirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cullen, Bernadette A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Deforce, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Delorme, RichardUNSPECIFIEDorcid.org/0000-0002-5614-3663UNSPECIFIED
Dion, YvesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Edlund, Christopher K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Egberts, KarinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Falkai, PeterUNSPECIFIEDorcid.org/0000-0003-2873-8667UNSPECIFIED
Fernandez, Thomas V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gallagher, Patience J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garrido, HelenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geller, DanielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Girard, Simon L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grabe, Hans J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Grados, Marco A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greenberg, Benjamin D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gross-Tsur, VardaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haddad, StephenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heiman, Gary A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hemmings, Sian M. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hounie, Ana G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Illmann, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jankovic, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jenike, Michael A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kennedy, James L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
King, Robert A.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
Macciardi, FabioUNSPECIFIEDorcid.org/0000-0003-0537-4266UNSPECIFIED
McCracken, James T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGrath, Lauren M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Restrepo, Sandra C. MesaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moessner, RainaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morgan, JubelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muller, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Murphy, Dennis L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Naarden, Allan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ochoa, William CornejoUNSPECIFIEDorcid.org/0000-0002-9065-8185UNSPECIFIED
Ophoff, Roel A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Osiecki, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pakstis, Andrew J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pato, Michele T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pato, Carlos N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piacentini, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pittenger, ChristopherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pollak, YehudaUNSPECIFIEDorcid.org/0000-0002-1293-499XUNSPECIFIED
Rauch, Scott L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Renner, Tobias J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reus, Victor I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Richter, Margaret A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riddle, Mark A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Robertson, Mary M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Romero, RoxanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosario, Maria C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenberg, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rouleau, Guy A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ruhrmann, StephanUNSPECIFIEDorcid.org/0000-0002-6022-2364UNSPECIFIED
Ruiz-Linares, AndresUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sampaio, Aline S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Samuels, JackUNSPECIFIEDorcid.org/0000-0002-6715-7905UNSPECIFIED
Sandor, PaulUNSPECIFIEDorcid.org/0000-0003-2397-0758UNSPECIFIED
Sheppard, BrookeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Singer, Harvey S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Smit, Jan H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stein, Dan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strengman, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tischfield, Jay A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duarte, Ana V. ValenciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vallada, HomeroUNSPECIFIEDorcid.org/0000-0001-5123-8295UNSPECIFIED
Van Nieuwerburgh, FilipUNSPECIFIEDorcid.org/0000-0001-8815-5485UNSPECIFIED
Veenstra-VanderWeele, JeremyUNSPECIFIEDorcid.org/0000-0002-6349-1076UNSPECIFIED
Walitza, SusanneUNSPECIFIEDorcid.org/0000-0002-8161-8683UNSPECIFIED
Wang, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wendland, Jens R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westenberg, Herman G. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shugart, Yin YaoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miguel, Euripedes C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McMahon, WilliamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagner, MichaelUNSPECIFIEDorcid.org/0000-0003-2589-6440UNSPECIFIED
Nicolini, HumbertoUNSPECIFIEDorcid.org/0000-0003-2494-0067UNSPECIFIED
Posthuma, DanielleUNSPECIFIEDorcid.org/0000-0001-7582-2365UNSPECIFIED
Hanna, Gregory L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heutink, PeterUNSPECIFIEDorcid.org/0000-0001-5218-1737UNSPECIFIED
Denys, DamiaanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, Paul D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oostra, Ben A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nestadt, GeraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freimer, Nelson B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pauls, David L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wray, Naomi R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stewart, S. EvelynUNSPECIFIEDorcid.org/0000-0002-0994-6383UNSPECIFIED
Mathews, Carol A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knowles, James A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cox, Nancy J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scharf, Jeremiah M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-475490
DOI: 10.1371/journal.pgen.1003864
Journal or Publication Title: PLoS Genet.
Volume: 9
Number: 10
Date: 2013
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1553-7404
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MISSING HERITABILITY; TIC DISORDERS; NEUROPSYCHIATRIC DISORDERS; GILLES; FAMILY; EXPRESSION; SCHOOL; PREVALENCE; AUTISM; RISKMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47549

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