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Rapid response to:

Clinical Review

Bipolar disorder

BMJ 2012; 345 doi: (Published 27 December 2012) Cite this as: BMJ 2012;345:e8508

Rapid Response:

Re: Bipolar disorder

Anderson and colleagues [1] state “Bipolar 1 disorder has a heritability of 0.75 explained largely by common variant alleles, which partly overlap with those of schizophrenia”. In fact very little of the heritability of bipolar disorder is explained by common polymorphisms. The largest genome wide association study (GWAS) of bipolar disorder[2] with 4387 cases and 6209 controls revealed an odds ratio of 1.45 for ANK3 (a gene involved in the function of voltage gated sodium channels) and 1.18 for CACNA1C (a gene which encodes a protein which is part of a voltage dependent calcium channel). Only the former achieved the GWAS threshold significance of less than 5 X 10-8.

The genetic basis of both bipolar disorder and schizophrenia is likely to be explained by the synergistic interaction of a small number of rare heterozygous deleterious mutations rather than the interaction of common variant alleles (3, 4). This will be revealed in the next generation of genetic studies using whole exome or whole genome screening.

Frances S Price
Medical Student
Faculty of Health and Medicine
Lancaster University

James A Morris
Consultant Pathologist
Associate Director of Undergraduate Medical Education
University Hospitals of Morecambe Bay NHS Foundation Trust
Royal Lancaster Infirmary
LA1 4RP.

The authors state they have no conflicts of interest

1. Anderson IA, Haddad PM, Scott J. Bipolar disorder. BMJ 2013;346: 27 – 32.
2. Ferreira MAR, Meng YA, Jones IR et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008; 40; 1056 – 58.
3. Morris JA. Synergistic interaction of heterozygous deletions impairs performance and confers susceptibility to disease at all ages. Medical Hypotheses 2005; 65: 483 – 493.
4. Price FS, Morris JA. Rare variants interact synergistically to impair complex networks and cause common disease: a model of the genetics of schizophrenia. Journal of Pathology 2012; 226: S14

Competing interests: No competing interests

17 January 2013
James A Morris
Consultant Pathologist
Frances S Price
University Hospitals of Morecambe Bay NHS Foundation Trust
Royal Lancaster Infirmary, Lancaster LA1 4RP