Family-based association study of early growth response gene 3 with child bipolar I disorder.

TitleFamily-based association study of early growth response gene 3 with child bipolar I disorder.
Publication TypeJournal Article
Year of Publication2012
AuthorsGallitano AL, Tillman R, Dinu V, Geller B
JournalJ Affect Disord
Volume138
Issue3
Pagination387-96
Date Published2012 May
ISSN1573-2517
KeywordsAdolescent, Bipolar Disorder, Child, Early Growth Response Protein 3, Early Growth Response Transcription Factors, Family, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Polymorphism, Single Nucleotide, Risk Factors
Abstract

BACKGROUND: The risk for relapse of child bipolar I disorder (BP-I) is highly correlated with environmental factors. Immediate early genes of the early growth response (EGR) gene family are activated at high levels in the brain in response to environmental events, including stress, and mediate numerous neurobiological processes that have been associated with mental illness risk. The objective of this study is to evaluate whether single nucleotide polymorphisms (SNPs) in EGR genes are associated with the risk to develop child bipolar I disorder.

METHODS: To investigate whether EGR genes may influence susceptibility to child bipolar I disorder (BP-I), we used Family Based Association Tests to examine whether SNPs in each of the EGR genes were associated with illness in 49 families.

RESULTS: Two SNPs in EGR3 displayed nominally significant associations with child BP-I (p=0.027 and p=0.028); though neither was statistically significant following correction for multiple comparisons. Haplotype association analysis indicated that these SNPs are in linkage disequilibrium (LD). None of the SNPs tested in EGR1, EGR2, or EGR4 was associated with child BP-I.

LIMITATIONS: This study was limited by small sample size, which resulted in it being underpowered to detect a significant association after correction for multiple comparisons.

CONCLUSIONS: Our study revealed a preliminary finding suggesting that EGR3, a gene that translates environmental stimuli into long-term changes in the brain, warrants further investigation for association with risk for child BP-I disorder in a larger sample. Such studies may help reveal mechanisms by which environment can interact with genetic predisposition to influence this severe mental illness.

DOI10.1016/j.jad.2012.01.011
Alternate JournalJ Affect Disord
PubMed ID22370066
PubMed Central IDPMC3349283
Grant ListR01 MH057451-01A2 / MH / NIMH NIH HHS / United States
R01 MH053063-05 / MH / NIMH NIH HHS / United States
MH-57451 / MH / NIMH NIH HHS / United States
L40 MH084542 / MH / NIMH NIH HHS / United States
MH-53063 / MH / NIMH NIH HHS / United States
R01 MH057451 / MH / NIMH NIH HHS / United States
R01 MH053063 / MH / NIMH NIH HHS / United States