Polygenic dissection of the bipolar phenotype

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 t...

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Published inBritish 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
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
BackgroundRecent 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.AimsTo test hypotheses about the relationship between schizophrenia and psychotic types of bipolar disorder.MethodUsing 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.ResultsThe 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.ConclusionsGenetic 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.
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.
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. Alms 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. Declaration of Interest None. Adapted from the source document.
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.
Author Grozeva, D
Jones, L
Owen, M J
St Clair, D
Sklar, P
Craddock, N
Jones, I R
Moskvina, V
Holmans, P A
McGuffin, P
Gurling, H
Green, E K
O'Donovan, M C
Hamshere, M L
Bass, N
Purcell, S
Young, A H
Farmer, A
Kirov, G
McQuillin, A
Ferrier, I N
AuthorAffiliation School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Newcastle upon Tyne, UK and UBC Institute of Mental Health, University Boulevard Vancouver, Canada
Institute of Psychiatry, King’s College London, UK
Department of Mental Health Sciences, University College London, UK
Department of Psychiatry, University of Birmingham, National Centre for Mental Health, Birmingham, UK
School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Newcastle upon Tyne, UK
Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, and Department of Psychiatry, Massachusetts General Hospital, Boston, and Stanley Center for Psychiatric Genetics, Broad Institute, Cambridge, Massachusetts, USA
MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, UK
University of Aberdeen, Institute of Medical Sciences, Aberdeen, UK
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Snippet Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic susceptibility for...
BackgroundRecent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic susceptibility...
Background Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic...
BACKGROUNDRecent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic susceptibility...
BACKGROUND: Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic...
Background Recent data provide strong support for a substantial common polygenic contribution (i.e. many alleles each of small effect) to genetic...
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Aggregation Database
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StartPage 284
SubjectTerms 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
Title Polygenic dissection of the bipolar phenotype
URI https://www.ncbi.nlm.nih.gov/pubmed/21972277
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https://pubmed.ncbi.nlm.nih.gov/PMC3065773
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