Common and rare variants of DAOA in bipolar disorder.

TitleCommon and rare variants of DAOA in bipolar disorder.
Publication TypeJournal Article
Year of Publication2009
AuthorsMaheshwari, M, Shi, J, Badner, JA, Skol, A, Willour, VL, Muzny, DM, Wheeler, DA, Gerald, FR, Detera-Wadleigh, S, McMahon, FJ, Potash, JB, Gershon, ES, Liu, C, Gibbs, RA
JournalAm J Med Genet B Neuropsychiatr Genet
Volume150B
Issue7
Pagination960-6
Date Published2009 Oct 05
ISSN1552-485X
KeywordsBipolar Disorder, Carrier Proteins, Cloning, Molecular, Exons, Female, Genetic Predisposition to Disease, Humans, Male, Polymorphism, Single Nucleotide, Sequence Analysis, DNA
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 association study in a sample of 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 may contribute to disease. 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.

DOI10.1002/ajmg.b.30925
Alternate JournalAm. J. Med. Genet. B Neuropsychiatr. Genet.
PubMed ID19194963
PubMed Central IDPMC2753761
Grant ListR01 MH061675 / MH / NIMH NIH HHS / United States
MH061675 / MH / NIMH NIH HHS / United States
MH 63420 / MH / NIMH NIH HHS / United States
R21 MH083521 / MH / NIMH NIH HHS / United States
MH60870 / MH / NIMH NIH HHS / United States
MH59586 / MH / NIMH NIH HHS / United States
MH059571 / MH / NIMH NIH HHS / United States
R01 MH042243 / MH / NIMH NIH HHS / United States
MH067257 / MH / NIMH NIH HHS / United States
R21 MH083521-01 / MH / NIMH NIH HHS / United States
R01 MH067257 / MH / NIMH NIH HHS / United States
R01 MH060870 / MH / NIMH NIH HHS / United States
R01MH061613 / MH / NIMH NIH HHS / United States
R01 MH059571 / MH / NIMH NIH HHS / United States
R01 MH059565 / MH / NIMH NIH HHS / United States
R01 MH042243-17 / MH / NIMH NIH HHS / United States
R01 MH059587 / MH / NIMH NIH HHS / United States
R01 MH061613 / MH / NIMH NIH HHS / United States
MH059565 / MH / NIMH NIH HHS / United States
R01 MH059586 / MH / NIMH NIH HHS / United States
MH059588 / MH / NIMH NIH HHS / United States
R01 MH059566 / MH / NIMH NIH HHS / United States
R01 MH061613-08 / MH / NIMH NIH HHS / United States
R01 MH063420 / MH / NIMH NIH HHS / United States
R01 MH059588 / MH / NIMH NIH HHS / United States
MH59566 / MH / NIMH NIH HHS / United States
1R21MH083521 / MH / NIMH NIH HHS / United States
U01 MH060879 / MH / NIMH NIH HHS / United States
R01 MH060879 / MH / NIMH NIH HHS / United States
MH59587 / MH / NIMH NIH HHS / United States