Re: Bipolar disorder
Anderson and colleagues  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 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
Faculty of Health and Medicine
James A Morris
Associate Director of Undergraduate Medical Education
University Hospitals of Morecambe Bay NHS Foundation Trust
Royal Lancaster Infirmary
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