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Polygenic dissection of the bipolar phenotype

  • M. L. Hamshere (a1), M. C. O'Donovan (a1), I. R. Jones (a1), L. Jones (a2), G. Kirov (a1), E. K. Green (a1), V. Moskvina (a1), D. Grozeva (a1), N. Bass (a3), A. McQuillin (a3), H. Gurling (a3), D. St Clair (a4), A. H. Young (a5), I. N. Ferrier (a6), A. Farmer (a7), P. McGuffin (a7), P. Sklar (a8), S. Purcell (a8), P. A. Holmans (a1), M. J. Owen (a1) and N. Craddock (a1)...
Abstract
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.

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Copyright
Corresponding author
Nick Craddock, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK. Email: craddockn@cardiff.ac.uk
Footnotes
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Funding for recruitment and phenotype assessment has been provided by the Wellcome Trust and the Medical Research Council. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. Funding for the project was provided by the Wellcome Trust under award 076113.

Declaration of interest

None.

Footnotes
References
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Polygenic dissection of the bipolar phenotype

  • M. L. Hamshere (a1), M. C. O'Donovan (a1), I. R. Jones (a1), L. Jones (a2), G. Kirov (a1), E. K. Green (a1), V. Moskvina (a1), D. Grozeva (a1), N. Bass (a3), A. McQuillin (a3), H. Gurling (a3), D. St Clair (a4), A. H. Young (a5), I. N. Ferrier (a6), A. Farmer (a7), P. McGuffin (a7), P. Sklar (a8), S. Purcell (a8), P. A. Holmans (a1), M. J. Owen (a1) and N. Craddock (a1)...
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