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

TitlePartitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
Authors
Issue Date2013
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
Citation
PLoS Genetics, 2013, v. 9 n. 10, article no. e1003864 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/200826
ISSN
2014 Impact Factor: 7.528
2015 SCImago Journal Rankings: 6.308
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDavis, LKen_US
dc.contributor.authoret al., 1en_US
dc.contributor.authorCampbell, DDen_US
dc.contributor.authoret al., 2en_US
dc.contributor.authorScharf, JMen_US
dc.date.accessioned2014-08-21T07:02:40Z-
dc.date.available2014-08-21T07:02:40Z-
dc.date.issued2013en_US
dc.identifier.citationPLoS Genetics, 2013, v. 9 n. 10, article no. e1003864en_US
dc.identifier.issn1553-7390en_US
dc.identifier.urihttp://hdl.handle.net/10722/200826-
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.en_US
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/en_US
dc.relation.ispartofPLoS Geneticsen_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong Licenseen_US
dc.titlePartitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architectureen_US
dc.typeArticleen_US
dc.identifier.emailCampbell, DD: ddc123@hku.hken_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1371/journal.pgen.1003864en_US
dc.identifier.pmid24204291en_US
dc.identifier.pmcidPMC3812053en_US
dc.identifier.hkuros232210en_US
dc.identifier.volume9en_US
dc.identifier.issue10en_US
dc.identifier.isiWOS:000330367200041-
dc.publisher.placeUnited Statesen_US

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