Singleton deletions throughout the genome increase risk of bipolar disorder

Mol Psychiatry. 2009 Apr;14(4):376-80. doi: 10.1038/mp.2008.144. Epub 2008 Dec 30.


An overall burden of rare structural genomic variants has not been reported in bipolar disorder (BD), although there have been reports of cases with microduplication and microdeletion. Here, we present a genome-wide copy number variant (CNV) survey of 1001 cases and 1034 controls using the Affymetrix single nucleotide polymorphism (SNP) 6.0 SNP and CNV platform. Singleton deletions (deletions that appear only once in the dataset) more than 100 kb in length are present in 16.2% of BD cases in contrast to 12.3% of controls (permutation P=0.007). This effect was more pronounced for age at onset of mania <or=18 years old. Our results strongly suggest that BD can result from the effects of multiple rare structural variants.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bipolar Disorder / genetics*
  • Case-Control Studies
  • Female
  • Gene Dosage
  • Genetic Predisposition to Disease*
  • Genome, Human / genetics*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Odds Ratio
  • Oligonucleotide Array Sequence Analysis / methods
  • Risk
  • Sequence Deletion / genetics*