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dc.contributor.authorRanlund, Siri
dc.contributor.authorCalafato, Stella
dc.contributor.authorThygesen, Johan H.
dc.contributor.authorLin, Kuang
dc.contributor.authorCahn, Wiepke
dc.contributor.authorCrespo-Facorro, Benedicto
dc.contributor.authorde Zwarte, Sonja M.C.
dc.contributor.authorDíez, Álvaro
dc.contributor.authorDi Forti, Marta
dc.contributor.authorIyegbe, Conrad
dc.contributor.authorJablensky, Assen
dc.contributor.authorJones, Rebecca
dc.contributor.authorHall, Mei-Hua
dc.contributor.authorKahn, Rene
dc.contributor.authorKalaydjieva, Luba
dc.contributor.authorKravariti, Eugenia
dc.contributor.authorMcDonald, Colm
dc.contributor.authorMcIntosh, Andrew M.
dc.contributor.authorMcQuillin, Andrew
dc.contributor.authorPicchioni, Marco
dc.contributor.authorPrata, Diana P.
dc.contributor.authorRujescu, Dan
dc.contributor.authorSchulze, Katja
dc.contributor.authorShaikh, Madiha
dc.contributor.authorToulopoulou, Timothea
dc.contributor.authorvan Haren, Neeltje
dc.contributor.authorvan Os, Jim
dc.contributor.authorVassos, Evangelos
dc.contributor.authorWalshe, Muriel
dc.contributor.authorLewis, Cathryn
dc.contributor.authorMurray, Robin M.
dc.contributor.authorPowell, John
dc.contributor.authorBramon, Elvira
dc.contributor.author,
dc.contributor.author,
dc.contributor.author,
dc.date.accessioned2018-09-20T16:22:25Z
dc.date.available2018-09-20T16:22:25Z
dc.date.issued2017-08-29
dc.identifier.citationRanlund, Siri; Calafato, Stella; Thygesen, Johan H. Lin, Kuang; Cahn, Wiepke; Crespo-Facorro, Benedicto; de Zwarte, Sonja M.C.; Díez, Álvaro; Di Forti, Marta; Iyegbe, Conrad; Jablensky, Assen; Jones, Rebecca; Hall, Mei-Hua; Kahn, Rene; Kalaydjieva, Luba; Kravariti, Eugenia; McDonald, Colm; McIntosh, Andrew M.; McQuillin, Andrew; Picchioni, Marco; Prata, Diana P.; Rujescu, Dan; Schulze, Katja; Shaikh, Madiha; Toulopoulou, Timothea; van Haren, Neeltje; van Os, Jim; Vassos, Evangelos; Walshe, Muriel; Lewis, Cathryn; Murray, Robin M.; Powell, John; Bramon, Elvira; , ; , ; , (2017). A polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 177 (1), 21-34
dc.identifier.issn1552-4841
dc.identifier.urihttp://hdl.handle.net/10379/13590
dc.description.abstractThis large multi-center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi-modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first-degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event-related potential (N=515), lateral ventricular volume (N=798), and the cognitive measures block design (N=3,089), digit span (N=1,437), and the Ray Auditory Verbal Learning Task (N=2,406). Data were collected across 11 sites in Europe and Australia; all genotyping and genetic analyses were done at the same laboratory in the United Kingdom. We calculated polygenic risk scores for schizophrenia and bipolar disorder separately, and used linear regression to test whether polygenic scores influenced the endophenotypes. Results showed that higher polygenic scores for schizophrenia were associated with poorer performance on the block design task and explained 0.2% (p=0.009) of the variance. Associations in the same direction were found for bipolar disorder scores, but this was not statistically significant at the 1% level (p=0.02). The schizophrenia score explained 0.4% of variance in lateral ventricular volumes, the largest across all phenotypes examined, although this was not significant (p=0.063). None of the remaining associations reached significance after correction for multiple testing (with alpha at 1%). These results indicate that common genetic variants associated with schizophrenia predict performance in spatial visualization, providing additional evidence that this measure is an endophenotype for the disorder with shared genetic risk variants. The use of endophenotypes such as this will help to characterize the effects of common genetic variation in psychosis.
dc.publisherWiley-Blackwell
dc.relation.ispartofAmerican Journal of Medical Genetics Part B: Neuropsychiatric Genetics
dc.subjectbipolar disorder
dc.subjectcognition
dc.subjecteeg
dc.subjectschizophrenia
dc.subjectsingle nucleotide polymorphism (snp)
dc.subjectgenome-wide association
dc.subjectevent-related potentials
dc.subjectunaffected 1st-degree relatives
dc.subjectedinburgh high-risk
dc.subjectbipolar disorder
dc.subjectworking-memory
dc.subjectpsychiatric-disorders
dc.subjectgenetic overlap
dc.subjectmaudsley family
dc.subjectwhite-matter
dc.titleA polygenic risk score analysis of psychosis endophenotypes across brain functional, structural, and cognitive domains
dc.typeArticle
dc.identifier.doi10.1002/ajmg.b.32581
dc.local.publishedsourcehttp://onlinelibrary.wiley.com/doi/10.1002/ajmg.b.32581/pdf
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