查看文章

Background: Bipolar disorder (BD) is a common, severe mood disorder that affects more than 1% of the worldwide population. Despite high heritability, the genetic architecture of BD remains elusive. While large genome-wide association studies (GWAS) identified dozens of BD loci, the role of rare variants of BD has not been studied on a large scale. This study aims to investigate whether rare, protein-altering single nucleotide variants (SNVs) contribute to the risk of BD. Specifically, we examined the exomes of 3,987 individuals with BD and 5,322 healthy controls to address the following questions: do individuals with BD carry a greater burden of rare coding variants (1) in their exomes overall;(2) in genes implicated by common variant GWAS in BD; and (3) in genes implicated through common and rare variant studies in schizophrenia (SCZ). We subsequently attempted replication of positive findings in an additional …