Polygenic dissection of the bipolar phenotype

• Published in: British journal of psychiatry Vol. 198; no. 4; pp. 284 - 288
• Main Authors: Hamshere, M L, O'Donovan, M C, Jones, I R, Jones, L, Kirov, G, Green, E K, Moskvina, V, Grozeva, D, Bass, N, McQuillin, A, Gurling, H, St Clair, D, Young, A H, Ferrier, I N, Farmer, A, McGuffin, P, Sklar, P, Purcell, S, Holmans, P A, Owen, M J, Craddock, N
• Format: Journal Article
• Language: English
• Published: England Cambridge University Press 01.04.2011; Royal College Of Psychiatrists
• Subjects: Adolescent; Alleles; Bipolar affective disorder; Bipolar disorder; Bipolar Disorder - diagnosis; Bipolar Disorder - genetics; Case-Control Studies; Consortia; Diagnostic and Statistical Manual of Mental Disorders; Dissection; Genetic Linkage; Genetic Predisposition to Disease; Genetic susceptibility; Genomes; Genotype; Genotype & phenotype; Humans; International Classification of Diseases; Logistic Models; Mental disorders; Multifactorial Inheritance; Phenotype; Phenotypes; Polymorphism, Single Nucleotide; Principal components analysis; Psychiatry; Psychoses; Psychosis; Psychotic Disorders - diagnosis; Psychotic Disorders - genetics; Psychotic symptoms; Replication; Schizophrenia; Schizophrenia - diagnosis; Schizophrenia - genetics; Susceptibility; United Kingdom; United Kingdom > UK
• ISSN: 0007-1250; 1472-1465
• DOI: 10.1192/bjp.bp.110.087866

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. To test hypotheses about the relationship between schizophrenia and psychotic types of bipolar disorder. 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. 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. 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.