Common and rare variants of DAOA in bipolar disorder

Manjula Maheshwari, Jiajun Shi, Judith A. Badner, Andrew Skol, Virginia L. Willour, Donna M. Muzny, David A. Wheeler, Fowler R. Gerald, Sevilla Detera-Wadleigh, Francis J. McMahon, James B. Potash, Elliot S. Gershon, Chunyu Liu, Richard A. Gibbs

Research output: Contribution to journalArticlepeer-review

Abstract

The D-amino acid oxidase activator (DAOA, previously known as G72) gene, mapped on 13q33, has been reported to be genetically associated with bipolar disorder (BP) in several populations. The consistency of associated variants is unclear and rare variants in exons of the DAOA gene have not been investigated in psychiatric diseases. We employed a conditional linkage method - STatistical Explanation for Positional Cloning (STEPC) to evaluate whether any associated single nucleotide polymorphisms (SNPs) account for the evidence of linkage in a pedigree series that previously has been linked to marker D13S779 at 13q33. We also performed an associationstudy in a sampleof 376 Caucasian BP parent-proband trios by genotyping 38 common SNPs in the gene region. Besides, we resequenced coding regions and flanking intronic sequences of DAOA in 555 Caucasian unrelated BP patients and 564 mentally healthy controls, to identify putative functional rare variants that maycontribute todisease. One SNP rs1935058 could "explain" the linkage signal in the family sample set (P=0.055) using STEPC analysis. No significant allelic association was detected in an association study by genotyping 38 common SNPs in 376 Caucasian BP trios. Resequencing identified 53 SNPs, of which 46 were novel SNPs. There was no significant excess of rare variants in cases relative to controls. Our results suggest that DAOA does not have a major effect on BP susceptibility. However, DAOA may contribute to bipolar susceptibility in some specific families as evidenced by the STEPC analysis.

Original languageEnglish (US)
Pages (from-to)960-966
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume150
Issue number7
DOIs
StatePublished - Oct 5 2009

Keywords

  • Bipolar disorder
  • DAOA
  • G72
  • Genetic association
  • Resequencing
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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