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Genetic Overlap of Schizophrenia and Bipolar Disorder in a High-Density Linkage Survey inthe Portuguese Island Population

2012-06Journal article Restricted access
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dc.contributor.authorFanous, Ayman H.
dc.contributor.authorMiddleton, Frank A.
dc.contributor.authorGentile, Karen
dc.contributor.authorAmdur, Richard L.
dc.contributor.authorMaher, Brion S.
dc.contributor.authorZhao, Zhongming
dc.contributor.authorSun, Jingchun
dc.contributor.authorMedeiros, Helena
dc.contributor.authorCarvalho, Célia
dc.contributor.authorFerreira, Susana R.
dc.contributor.authorMacedo, António
dc.contributor.authorKnowles, James A.
dc.contributor.authorAzevedo, Maria H.
dc.contributor.authorPato, Michele T.
dc.contributor.authorPato, Carlos N.
dc.date.accessioned2017-02-23T18:55:46Z
dc.date.available2017-02-23T18:55:46Z
dc.date.issued2012-06
dc.description.abstractRecent family and genome-wide association studies strongly suggest shared genetic risk factors for schizophrenia (SZ) and bipolar disorder (BP). However, linkage studies have not been used to test for statistically significant genome-wide overlap between them. Forty-seven Portuguese families with sibpairs concordant for SZ, BP, or psychosis (PSY, which includes either SZ or psychotic BP) were genotyped for over 57,000 markers using the Affymetrix 50K Xba SNP array. NPL and Kong and Cox LOD scores were calculated in Merlin for all three phenotypes. Empirical significance was determined using 1,000 gene-dropping simulations. Significance of genome-wide genetic overlap between SZ and BP was determined by the number of simulated BP scans having the same number of loci jointly linked with the real SZ scan, and vice versa. For all three phenotypes, a number of regions previously linked in this sample remained so. For BP, chromosome 1p36 achieved significance (11.54-15.71 MB, LOD = 3.51), whereas it was not even suggestively linked at lower marker densities, as did chromosome 11q14.1 (89.32-90.15 MB, NPL = 4.15). Four chromosomes had loci at which both SZ and BP had NPL ≥ 1.98, which was more than would be expected by chance (empirical P = 0.01 using simulated SZ scans; 0.07 using simulated BP scans), although they did not necessarily meet criteria for suggestive linkage individually. These results suggest that high-density marker maps may provide greater power and precision in linkage studies than lower density maps. They also further support the hypothesis that SZ and BP share at least some risk alleles.en
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFanous, A.H., Middleton, F.A., Gentile, K., Amdur, R.L., Maher, B.S., Zhao, Z., Sun, J., Medeiros, H., Carvalho, C., Ferreira, S.R., Macedo, A., Knowles, J.A., Azevedo, M.H., Pato, M.T., Pato, C.N. (2012). Genetic Overlap of Schizophrenia and Bipolar Disorder in a High-Density Linkage Survey inthe Portuguese Island Population. "American Journal of Medical Genetics Part B: Neuropsychiatric Genetics", 159B(4), 383–391.en
dc.identifier.doi10.1002/ajmg.b.32041pt_PT
dc.identifier.issn1552-485X
dc.identifier.urihttp://hdl.handle.net/10400.3/3996
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley and Sonsen
dc.relation.publisherversionhttp://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.32041/abstractpt_PT
dc.subjectBipolar Disorderen
dc.subjectSchizophreniaen
dc.titleGenetic Overlap of Schizophrenia and Bipolar Disorder in a High-Density Linkage Survey inthe Portuguese Island Populationen
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage391pt_PT
oaire.citation.issue(4)pt_PT
oaire.citation.startPage383pt_PT
oaire.citation.titleAmerican Journal of Medical Genetics Part B: Neuropsychiatric Geneticsen
oaire.citation.volume159Bpt_PT
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT

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