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dc.contributor.authorQUINN, EMMAen
dc.contributor.authorKENNY, ELAINEen
dc.contributor.authorCORVIN, AIDENen
dc.contributor.authorGILL, MICHAELen
dc.contributor.authorMORRIS, DEREKen
dc.date.accessioned2011-06-21T13:18:02Z
dc.date.available2011-06-21T13:18:02Z
dc.date.issued2010en
dc.date.submitted2010en
dc.identifier.citationRaychaudhuri S, Korn JM, McCarroll SA, International Schizophrenia Consortium, Altshuler D, Sklar P, Purcell S, Daly MJ, Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function., PLoS genetics, 6, 9, e1001097, 2010en
dc.identifier.issn1553-7390en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/57167
dc.descriptionPUBLISHEDen
dc.descriptionPMID: 20838587en
dc.description.abstractInvestigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied ``pathway?? analyses to genes within neuropsychiatric case CNVs to show enrichment for brainfunctions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnvenrichment- test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package.en
dc.description.sponsorshipFor this work, SR is supported by a K08 National Institutes of Health (NIH) career development award (AR055688). MJD is supported by NIH grants through the U01 (HG004171, DK62432) and R01 (DK083756-1, DK64869) mechanisms. The MIGen study was funded by funding from the NIH-NLBI (R01HL087676) and a grant from the National Center for Research Resources. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripten
dc.language.isoenen
dc.relation.ispartofseriesPLoS geneticsen
dc.relation.ispartofseries6en
dc.relation.ispartofseries9, e1001097en
dc.rightsYen
dc.subjectNeuroscienceen
dc.subjectneuronal-activityen
dc.titleAccurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/morrisdwen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/acorvinen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kennyelen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mgillen
dc.identifier.rssinternalid69988en
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pgen.1001097en
dc.subject.TCDThemeGenes & Societyen
dc.subject.TCDThemeNeuroscienceen
dc.identifier.rssurihttp://dx.doi.org/10.1371/journal.pgen.1001097en


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