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Polygenic dissection of the bipolar phenotype

Hamshere, Marian Lindsay ORCID:, O'Donovan, Michael Conlon ORCID:, Jones, Ian Richard ORCID:, Jones, L., Kirov, George ORCID:, Green, Elaine Karen, Escott-Price, Valentina ORCID:, Grozeva, Detelina ORCID:, Bass, N., McQuillin, A., Gurling, H., St Clair, D., Young, A. H., Ferrier, I. N., Farmer, Anne, McGuffin, Peter, Sklar, P., Purcell, S., Holmans, Peter Alan ORCID:, Owen, Michael John ORCID: and Craddock, Nicholas John ORCID: 2011. Polygenic dissection of the bipolar phenotype. British Journal of Psychiatry 198 (4) , pp. 284-288. 10.1192/bjp.bp.110.087866

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Background Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic susceptibility for schizophrenia and overlapping susceptibility for bipolar disorder. Aims To test hypotheses about the relationship between schizophrenia and psychotic types of bipolar disorder. Method Using a polygenic score analysis to test whether schizophrenia polygenic risk alleles, en masse, significantly discriminate between individuals with bipolar disorder with and without psychotic features. The primary sample included 1829 participants with bipolar disorder and the replication sample comprised 506 people with bipolar disorder. Results The subset of participants with Research Diagnostic Criteria schizoaffective bipolar disorder (n = 277) were significantly discriminated from the remaining participants with bipolar disorder (n = 1552) in both the primary (P = 0.00059) and the replication data-sets (P = 0.0070). In contrast, those with psychotic bipolar disorder as a whole were not significantly different from those with non-psychotic bipolar disorder in either data-set. Conclusions Genetic susceptibility influences at least two major domains of psychopathological variation in the schizophrenia–bipolar disorder clinical spectrum: one that relates to expression of a ‘bipolar disorder-like’ phenotype and one that is associated with expression of ‘ schizophrenia-like’ psychotic symptoms.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Royal College of Psychiatrists
ISSN: 0007-1250
Last Modified: 06 Nov 2022 14:14

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