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New Developments in the Genetics of Bipolar Disorder

  • Bipolar Disorders (W Coryell, Section Editor)
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Abstract

The last several years have been breakthrough ones in bipolar disorder (BPD) genetics, as the field has identified robust risk variants for the first time. Leading the way have been genome-wide association studies (GWAS) that have assessed common genetic markers across very large groups of patients and controls. These have resulted in findings in genes including ANK3, CACNA1C, SYNE1, ODZ4, and TRANK1. Additional studies have begun to examine the biology of these genes and how risk variants influence aspects of brain and behavior that underlie BPD. For example, carriers of the CACNA1C risk variant have been found to exhibit hippocampal and anterior cingulate dysfunction during episodic memory recall. This work has shed additional light on the relationship of bipolar susceptibility variants to other disorders, particularly schizophrenia. Even larger BPD GWAS are expected with samples now amassed of 21,035 cases and 28,758 controls. Studies have examined the pharmacogenomics of BPD with studies of lithium response, yielding high profile results that remain to be confirmed. The next frontier in the field is the identification of rare bipolar susceptibility variants through large-scale DNA sequencing. While only a couple of papers have been published to date, many studies are underway. The Bipolar Sequencing Consortium has been formed to bring together all of the groups working in this area, and to perform meta-analyses of the data generated. The consortium, with 13 member groups, now has exome data on ~3,500 cases and ~5,000 controls, and on ~162 families. The focus will likely shift within several years from exome data to whole genome data as costs of obtaining such data continue to drop. Gene-mapping studies are now providing clear results that provide insights into the pathophysiology of the disorder. Sequencing studies should extend this process further. Findings could eventually set the stage for rational therapeutic development.

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Acknowledgements

This work was supported by a grant from the NIMH to Dr. Potash (R01MH087979). The authors report no competing interests.

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Gen Shinozaki and James B. Potash declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA

    Gen Shinozaki & James B. Potash

  2. University of Iowa Hospitals and Clinics, 200 Hawkins Drive, 2887 JPP, Iowa City, IA, 52242, USA

    James B. Potash

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  1. Gen Shinozaki
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  2. James B. Potash
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Correspondence to James B. Potash.

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This article is part of the Topical Collection on Bipolar Disorders

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Shinozaki, G., Potash, J.B. New Developments in the Genetics of Bipolar Disorder. Curr Psychiatry Rep 16, 493 (2014). https://doi.org/10.1007/s11920-014-0493-5

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