TY - JOUR
T1 - Family-based association study of early growth response gene 3 with child bipolar i disorder
AU - Gallitano, Amelia L.
AU - Tillman, Rebecca
AU - Dinu, Valentin
AU - Geller, Barbara
N1 - Funding Information:
This work was supported by the Pfizer Fellowship in Biological Psychiatry Grant (to ALG), a NARSAD/Sidney R Baer Jr. Foundation Young Investigator Award (to ALG), an ASU/Mayo Clinic Seed Grant (to VD), NIMH MH-53063 (to BG), MH-57451 (to BG), and the Theodore and Vada Stanley Foundation (to BG). None of these funding sources had any further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
Funding Information:
We are grateful to Edwin H. Cook, Jr., M.D., University of Illinois, Chicago, for prior isolation of DNA from blood samples, En-Tan Zhang, M.D., Ph.D., Leela Muppana, M.S., and Mohammad Torabi, Ph.D., and Amber Monib, University of Arizona College of Medicine — Phoenix, for technical and statistical assistance, and Jeffrey Sutherland, B.S., NIDDK, for assistance with the SNPlex protocol. This work was supported by the Pfizer Fellowship in Biological Psychiatry Grant (to ALG), a NARSAD/Sidney R Baer Jr. Foundation Young Investigator Award (to ALG), an ASU/Mayo Clinic Seed Grant (to VD), NIMH MH-53063 (to BG), MH-57451 (to BG), and the Theodore and Vada Stanley Foundation (to BG).
PY - 2012/5
Y1 - 2012/5
N2 - 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.
AB - 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.
KW - Child bipolar I disorder
KW - Early growth response gene 3
KW - Environment
KW - Family Based Association Test
KW - Immediate early gene
KW - Stress
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U2 - 10.1016/j.jad.2012.01.011
DO - 10.1016/j.jad.2012.01.011
M3 - Article
C2 - 22370066
AN - SCOPUS:84858285171
SN - 0165-0327
VL - 138
SP - 387
EP - 396
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
IS - 3
ER -