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

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dc.contributor.authorDavis, Lea K
dc.contributor.authorYu, Dongmei
dc.contributor.authorKeenan, Clare L
dc.contributor.authorGamazon, Eric R
dc.contributor.authorKonkashbaev, Anuar I
dc.contributor.authorDerks, Eske M
dc.contributor.authorNeale, Benjamin M
dc.contributor.authorYang, Jian
dc.contributor.authorLee, S Hong
dc.contributor.authorEvans, Patrick
dc.contributor.authorBarr, Cathy L
dc.contributor.authorBellodi, Laura
dc.contributor.authorBenarroch, Fortu
dc.contributor.authorBerriĆ³, Gabriel Bedoya
dc.contributor.authorBienvenu, Oscar J
dc.contributor.authorBloch, Michael H
dc.contributor.authorBlom, Rianne M
dc.contributor.authorBruun, Ruth D
dc.contributor.authorBudman, Cathy L
dc.contributor.authorCamarena, Beatriz
dc.contributor.authorCampbell, Desmond
dc.contributor.authorCappi, Carolina
dc.contributor.authorCardona Silgado, Julio C
dc.contributor.authorCath, Danielle C
dc.contributor.authorCavallini, Maria C
dc.contributor.authorChavira, Denise A
dc.contributor.authorChouinard, Sylvain
dc.contributor.authorConti, David V
dc.contributor.authorCook, Edwin H
dc.contributor.authorCoric, Vladimir
dc.contributor.authorCullen, Bernadette A
dc.contributor.authorDeforce, Dieter
dc.date.accessioned2021-10-08T07:11:55Z
dc.date.available2021-10-08T07:11:55Z
dc.date.issued2013
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.identifier.apacitationDavis, L. K., Yu, D., Keenan, C. L., Gamazon, E. R., Konkashbaev, A. I., Derks, E. M., ... Deforce, D. (2013). Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture. <i>PLoS Genetics</i>, 9(10), e1003864 - 177. http://hdl.handle.net/11427/34708en_ZA
dc.identifier.chicagocitationDavis, Lea K, Dongmei Yu, Clare L Keenan, Eric R Gamazon, Anuar I Konkashbaev, Eske M Derks, Benjamin M Neale, et al "Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture." <i>PLoS Genetics</i> 9, 10. (2013): e1003864 - 177. http://hdl.handle.net/11427/34708en_ZA
dc.identifier.citationDavis, L.K., Yu, D., Keenan, C.L., Gamazon, E.R., Konkashbaev, A.I., Derks, E.M., Neale, B.M. & Yang, J. et al. 2013. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture. <i>PLoS Genetics.</i> 9(10):e1003864 - 177. http://hdl.handle.net/11427/34708en_ZA
dc.identifier.issn1553-7390
dc.identifier.issn1553-7404
dc.identifier.ris TY - Journal Article AU - Davis, Lea K AU - Yu, Dongmei AU - Keenan, Clare L AU - Gamazon, Eric R AU - Konkashbaev, Anuar I AU - Derks, Eske M AU - Neale, Benjamin M AU - Yang, Jian AU - Lee, S Hong AU - Evans, Patrick AU - Barr, Cathy L AU - Bellodi, Laura AU - Benarroch, Fortu AU - BerriĆ³, Gabriel Bedoya AU - Bienvenu, Oscar J AU - Bloch, Michael H AU - Blom, Rianne M AU - Bruun, Ruth D AU - Budman, Cathy L AU - Camarena, Beatriz AU - Campbell, Desmond AU - Cappi, Carolina AU - Cardona Silgado, Julio C AU - Cath, Danielle C AU - Cavallini, Maria C AU - Chavira, Denise A AU - Chouinard, Sylvain AU - Conti, David V AU - Cook, Edwin H AU - Coric, Vladimir AU - Cullen, Bernadette A AU - Deforce, Dieter AB - 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. DA - 2013 DB - OpenUCT DP - University of Cape Town IS - 10 J1 - PLoS Genetics LK - https://open.uct.ac.za PY - 2013 SM - 1553-7390 SM - 1553-7404 T1 - Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture TI - Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture UR - http://hdl.handle.net/11427/34708 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34708
dc.identifier.vancouvercitationDavis LK, Yu D, Keenan CL, Gamazon ER, Konkashbaev AI, Derks EM, et al. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture. PLoS Genetics. 2013;9(10):e1003864 - 177. http://hdl.handle.net/11427/34708.en_ZA
dc.publisher.departmentDepartment of Psychiatry and Mental Health
dc.publisher.facultyFaculty of Health Sciences
dc.sourcePLoS Genetics
dc.source.journalissue10
dc.source.journalvolume9
dc.source.paginatione1003864 - 177
dc.source.urihttps://dx.doi.org/10.1371/journal.pgen.1003864
dc.subject.otherSocial and Behavioral Sciences
dc.subject.otherCenter for Child and Adolescent Psychiatry
dc.subject.otherResearch Article
dc.subject.otherEXPRESSION
dc.subject.otherBiology and Life Sciences
dc.subject.other610 Medicine &
dc.subject.otherhealth
dc.subject.otherSettore MED/03 - Genetica Medica
dc.subject.otherBRAIN
dc.subject.otherGILLES
dc.subject.otherAUTISM
dc.subject.otherQH426-470
dc.subject.otherGenetics
dc.subject.otherCOMPLEX DISEASES
dc.subject.otherNEUROPSYCHIATRIC DISORDERS
dc.subject.otherLife Sciences
dc.subject.otherMedicine and Health Sciences
dc.subject.otherMISSING HERITABILITY
dc.subject.otherTIC DISORDERS
dc.subject.otherFAMILY
dc.subject.othermissing heritability
dc.subject.otherTIC disorders
dc.subject.otherneuropsychiatric disorders
dc.subject.othercomplex diseases
dc.subject.othercommon SNPS
dc.subject.othergilles
dc.subject.otherfamily
dc.subject.otherbrain
dc.subject.otherexpression
dc.subject.otherautism
dc.subject.otherCOMMON SNPS
dc.titlePartitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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