Neurocognitive Endophenotypes for Bipolar Disorder Identified in Multiplex Multigenerational Families

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Abstract
Despite considerable evidence that the risk for bipolar disorder is inherited, the molecular genetic basis for this illness remains elusive. A recent genome-wide association analysis with more than 5000 cases and 6000 control subjects implicated 2 risk genes for the illness: ANK3 and CACNA1C.1 Because these genes regulate voltage-gated sodium and calcium channels, respectively, the findings suggest that ion channel dysfunction may play an important role in the pathophysiologic process of bipolar disorder. However, as noted by the authors, these genes have relatively small risk ratios, explaining little of the genetic contribution to the illness. Given the high heritability and familial relative risk of bipolar disorder, there is little doubt that additional genes are involved in the etiology of the illness. The identification of these genes is of paramount importance because they hold the potential for spurring novel treatments for this common and debilitating illness.