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Genome-wide associa...
Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder
- Article/chapterEnglish2012
Publisher, publication year, extent ...
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2012-06-12
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Springer Science and Business Media LLC,2012
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LIBRIS-ID:oai:gup.ub.gu.se/164060
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https://gup.ub.gu.se/publication/164060URI
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https://doi.org/10.1038/mp.2012.73DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:125144165URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Schizophrenia (SCZ) and bipolar disorder (BD) are highly heritable psychiatric disorders with overlapping susceptibility loci and symptomatology. We conducted a genome-wide association study (GWAS) of these disorders in a large Swedish sample. We report a new and independent case-control analysis of 1507 SCZ cases, 836 BD cases and 2093 controls. No single-nucleotide polymorphisms (SNPs) achieved significance in these new samples; however, combining new and previously reported SCZ samples (2111 SCZ and 2535 controls) revealed a genome-wide significant association in the major histocompatibility complex (MHC) region (rs886424, P = 4.54 x 10(-8)). Imputation using multiple reference panels and meta-analysis with the Psychiatric Genomics Consortium SCZ results underscored the broad, significant association in the MHC region in the full SCZ sample. We evaluated the role of copy number variants (CNVs) in these subjects. As in prior reports, deletions were enriched in SCZ, but not BD cases compared with controls. Singleton deletions were more frequent in both case groups compared with controls (SCZ: P = 0.003, BD: P = 0.013), whereas the largest CNVs (>500 kb) were significantly enriched only in SCZ cases (P = 0.0035). Two CNVs with previously reported SCZ associations were also overrepresented in this SCZ sample: 16p11.2 duplications (P = 0.0035) and 22q11 deletions (P = 0.03). These results reinforce prior reports of significant MHC and CNV associations in SCZ, but not BD.
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O'Dushlaine, C. T.
(author)
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Ripke, S.
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Lee, P. H.
(author)
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Ruderfer, D. M.
(author)
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Akterin, S.
(author)
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Moran, J. L.Karolinska Institutet
(author)
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Chambert, K. D.
(author)
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Handsaker, R. E.
(author)
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Backlund, L.Karolinska Institutet
(author)
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Osby, U.Karolinska Institutet
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McCarroll, S.
(author)
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Landén, Mikael,1966Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry(Swepub:gu)xlandt
(author)
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Scolnick, E. M.
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Magnusson, P. K. E.Karolinska Institutet
(author)
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Lichtenstein, P.Karolinska Institutet
(author)
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Hultman, C. M.Karolinska Institutet
(author)
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Purcell, S. M.
(author)
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Sklar, P.
(author)
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Sullivan, P. F.Karolinska Institutet
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Karolinska InstitutetInstitutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
(creator_code:org_t)
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In:Molecular Psychiatry: Springer Science and Business Media LLC17:9, s. 880-8861359-41841476-5578
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Bergen, S. E.
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O'Dushlaine, C. ...
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Ripke, S.
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Lee, P. H.
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Ruderfer, D. M.
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Akterin, S.
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Moran, J. L.
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Chambert, K. D.
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Handsaker, R. E.
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Backlund, L.
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Osby, U.
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McCarroll, S.
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Landén, Mikael, ...
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Scolnick, E. M.
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Magnusson, P. K. ...
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Lichtenstein, P.
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Hultman, C. M.
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Purcell, S. M.
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Sklar, P.
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Sullivan, P. F.
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and Psychiatry
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Molecular Psychi ...
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University of Gothenburg
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Karolinska Institutet