Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture

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dc.contributor.authorDavis, Lea K.en_ZA
dc.contributor.authorYu, Dongmeien_ZA
dc.contributor.authorKeenan, Clare L.en_ZA
dc.contributor.authorGamazon, Eric R.en_ZA
dc.contributor.authorKonkashbaev, Anuar I.en_ZA
dc.contributor.authorDerks, Eske M.en_ZA
dc.contributor.authorNeale, Benjamin M.en_ZA
dc.contributor.authorYang, Jianen_ZA
dc.contributor.authorLee, S. Hongen_ZA
dc.contributor.authorEvans, Patricken_ZA
dc.contributor.authorBarr, Cathy L.en_ZA
dc.contributor.authorBellodi, Lauraen_ZA
dc.contributor.authorBenarroch, Fortuen_ZA
dc.contributor.authorBerrio, Gabriel Bedoyaen_ZA
dc.contributor.authorBienvenu, Oscar J.en_ZA
dc.contributor.authorBloch, Michael H.en_ZA
dc.contributor.authorBlom, Rianne M.en_ZA
dc.contributor.authorBruun, Ruth D.en_ZA
dc.contributor.authorBudman, Cathy L.en_ZA
dc.contributor.authorCamarena, Beatrizen_ZA
dc.contributor.authorCampbell, Desmonden_ZA
dc.contributor.authorCappi, Carolinaen_ZA
dc.contributor.authorSilgado, Julio C. Cardonaen_ZA
dc.contributor.authorCath, Danielle C.en_ZA
dc.contributor.authorCavallini, Maria C.en_ZA
dc.contributor.authorChavira, Denise A.en_ZA
dc.contributor.authorChouinard, Sylvainen_ZA
dc.contributor.authorConti, David. V.en_ZA
dc.contributor.authorCook, Edwin H.en_ZA
dc.contributor.authorCoric, Vladimiren_ZA
dc.contributor.authorCullen, Bernadette A.en_ZA
dc.contributor.authorDeforce, Dieteren_ZA
dc.contributor.authorDelorme, Richarden_ZA
dc.contributor.authorDion, Yvesen_ZA
dc.contributor.authorEdlund, Christopher K.en_ZA
dc.contributor.authorEgberts, Karinen_ZA
dc.contributor.authorFalkai, Peteren_ZA
dc.contributor.authorFernandez, Thomas V.en_ZA
dc.contributor.authorGallagher, Patience J.en_ZA
dc.contributor.authorGarrido, Helenaen_ZA
dc.contributor.authorGeller, Danielen_ZA
dc.contributor.authorGirard, Simon L.en_ZA
dc.contributor.authorGrabe, Hans J.en_ZA
dc.contributor.authorGrados, Marco A.en_ZA
dc.contributor.authorGreenberg, Benjamin D.en_ZA
dc.contributor.authorGross-Tsur, Vardaen_ZA
dc.contributor.authorHaddad, Stephenen_ZA
dc.contributor.authorHeiman, Gary A.en_ZA
dc.contributor.authorHemmings, Sian M. J.en_ZA
dc.contributor.authorHounie, Ana G.en_ZA
dc.contributor.authorIllmann, Corneliaen_ZA
dc.contributor.authorJankovic, Josephen_ZA
dc.contributor.authorJenike, Michael A.en_ZA
dc.contributor.authorKennedy, James L.en_ZA
dc.contributor.authorKing, Robert A.en_ZA
dc.contributor.authorKremeyer, Barbaraen_ZA
dc.contributor.authorKurlan, Rogeren_ZA
dc.contributor.authorLanzagorta, Nuriaen_ZA
dc.contributor.authorLeboyer, Marionen_ZA
dc.contributor.authorLeckman, James F.en_ZA
dc.contributor.authorLennertz, Leonharden_ZA
dc.contributor.authorLiu, Chunyuen_ZA
dc.contributor.authorLochner, Christineen_ZA
dc.contributor.authorLowe, Thomas L.en_ZA
dc.contributor.authorMacciardi, Fabioen_ZA
dc.contributor.authorMcCracken, James T.en_ZA
dc.contributor.authorMcGrath, Lauren M.en_ZA
dc.contributor.authorMesa Restrepo, Sandra C.en_ZA
dc.contributor.authorMoessner, Rainalden_ZA
dc.contributor.authorMorgan, Jubelen_ZA
dc.contributor.authorMuller, Heikeen_ZA
dc.contributor.authorMurphy, Dennis L.en_ZA
dc.contributor.authorNaarden, Allan L.en_ZA
dc.contributor.authorOchoa, William Cornejoen_ZA
dc.contributor.authorOphoff, Roel A.en_ZA
dc.contributor.authorOsiecki, Lisaen_ZA
dc.contributor.authorPakstis, Andrew J.en_ZA
dc.contributor.authorPato, Michele T.en_ZA
dc.contributor.authorPato, Carlos N.en_ZA
dc.contributor.authorPiacentini, Johnen_ZA
dc.contributor.authorPittenger, Christopheren_ZA
dc.contributor.authorPollak, Yehudaen_ZA
dc.contributor.authorRauch, Scott L.en_ZA
dc.contributor.authorRenner, Tobias J.en_ZA
dc.contributor.authorReus, Victor I.en_ZA
dc.contributor.authorRichter, Margaret A.en_ZA
dc.contributor.authorRiddle, Mark A.en_ZA
dc.contributor.authorRobertson, Mary M.en_ZA
dc.contributor.authorRomero, Roxanaen_ZA
dc.contributor.authorRosario, Maria C.en_ZA
dc.contributor.authorRosenberg, Daviden_ZA
dc.contributor.authorRouleau, Guy A.en_ZA
dc.contributor.authorRuhrmann, Stephanen_ZA
dc.contributor.authorRuiz-Linares, Andresen_ZA
dc.contributor.authorSampaio, Aline S.en_ZA
dc.contributor.authorSamuels, Jacken_ZA
dc.contributor.authorSandor, Paulen_ZA
dc.contributor.authorSheppard, Brookeen_ZA
dc.contributor.authorSinger, Harvey S.en_ZA
dc.contributor.authorSmit, Jan H.en_ZA
dc.contributor.authorStein, Dan J.en_ZA
dc.contributor.authorStrengman, E.en_ZA
dc.contributor.authorTischfield, Jay A.en_ZA
dc.contributor.authorValencia Duarte, Ana V.en_ZA
dc.contributor.authorVallada, Homeroen_ZA
dc.contributor.authorVan Nieuwerburgh, Filipen_ZA
dc.contributor.authorVeenstra-VanderWeele, Jeremyen_ZA
dc.contributor.authorWalitza, Susanneen_ZA
dc.contributor.authorWang, Yingen_ZA
dc.contributor.authorWendland, Jens R.en_ZA
dc.contributor.authorWestenberg, Herman G. M.en_ZA
dc.contributor.authorShugart, Yin Yaoen_ZA
dc.contributor.authorMiguel, Euripedes C.en_ZA
dc.contributor.authorMcMahon, Williamen_ZA
dc.contributor.authorWagner, Michaelen_ZA
dc.contributor.authorNicolini, Humbertoen_ZA
dc.contributor.authorPosthuma, Danielleen_ZA
dc.contributor.authorHanna, Gregory L.en_ZA
dc.contributor.authorHeutnik, Peteren_ZA
dc.contributor.authorDenys, Damiaanen_ZA
dc.contributor.authorArnold, Paul D.en_ZA
dc.contributor.authorOostra, Ben A.en_ZA
dc.contributor.authorNestadt, Geralden_ZA
dc.contributor.authorFreimer, Nelson B.en_ZA
dc.contributor.authorPauls, David L.en_ZA
dc.contributor.authorWray, Naomi R.en_ZA
dc.contributor.authorStewart, S. Evelynen_ZA
dc.contributor.authorMathews, Carol A.en_ZA
dc.contributor.authorKnowles, James A.en_ZA
dc.contributor.authorCox, Nancy J.en_ZA
dc.contributor.authorShcarf, Jeremiah M.en_ZA
dc.date.accessioned2014-07-07T12:35:53Z
dc.date.available2014-07-07T12:35:53Z
dc.date.issued2013-10
dc.descriptionCITATION: Davis, L.K. et al. 2013. Partitioning the heritability of Tourette Syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genetics, 9(10):e1003864, doi:10.1371/journal.pgen.1003864.en_ZA
dc.descriptionThe original publication is available at http://journals.plos.org/plosgenetics
dc.description.abstractThe 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.
dc.description.urihttp://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1003864
dc.description.versionPublisher's version
dc.format.extent14 pages
dc.identifier.citationDavis, L.K. et al. 2013. Partitioning the heritability of Tourette Syndrome and obsessive compulsive disorder reveals differences in genetic architecture. PLoS Genetics, 9(10):e1003864, doi:10.1371/journal.pgen.1003864.en_ZA
dc.identifier.issn1553-7404 (online)
dc.identifier.otherdoi:10.1371/journal.pgen.1003864
dc.identifier.urihttp://hdl.handle.net/10019.1/95374
dc.publisherPLoSen_ZA
dc.rights.holderAuthors retain copyright
dc.subjectTourette syndrome -- Genetic aspectsen_ZA
dc.subjectObsessive-compulsive disorder -- Genetic aspectsen_ZA
dc.titlePartitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architectureen_ZA
dc.typeArticleen_ZA
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