Heterogeneity analysis provides evidence for a genetically homogeneous subtype of bipolar-disorder

Abstract

Bipolar disorder is a highly heritable brain disorder which affects an estimated 50 million people worldwide. Due to recent advances in genotyping technology and bioinformatics methodology, as well as the increase in the overall amount of available data, our understanding of the genetic underpinnings of BD has improved. A growing consensus is that BD is polygenic and heterogeneous, but the specifics of that heterogeneity are not yet well understood. Here we use a recently developed technique to investigate the genetic heterogeneity of bipolar disorder. We find strong statistical evidence for a `bicluster': a subset of bipolar subjects that exhibits a disease-specific genetic pattern. The structure illuminated by this bicluster replicates in several other data-sets and can be used to improve BD risk-prediction algorithms. We believe that this bicluster is likely to correspond to a genetically-distinct subtype of BD. More generally, we believe that our biclustering approach is a promising means of untangling the underlying heterogeneity of complex disease without the need for reliable subphenotypic data.