Study Report

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Basic Info

Reference	Gallitano, A. L.,2012 PMID: 22370066
Citation	Gallitano, A. L., R. Tillman, et al. (2012). "Family-based association study of early growth response gene 3 with child bipolar I disorder." J Affect Disord 138(3): 387-396.
Disease Type	Bipolar I Disorder
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	49 child BP-I families
SNP/Region/Marker Size	28 SNPs
Predominant Ethnicity
Population	American
Gender	67.3% males
Age Group	Adolescents : Mean age(SD)(year):10.9(2.8)

Detail Info

Sample Diagnosis	DSM
Sample Status	Subjects met the inclusion criteria of 7 to 16 years old, males and females, good physical health, and a diagnosis of current DSM-IV BP-I (manic or mixed phase) for at least 2 weeks with at least 1 cardinal symptom of mania (i.e., elation and/or grandiosity) (Geller et al., 2008). A Children's Global Assessment Scale (CGAS) score of >= 60 was required to establish clinically significant impairment (Bird et al.,1987; Shaffer et al., 1983). DNA samples were previously collected, and isolated from whole blood, from a cohort of families of child BP-I patients (Geller et al., 2002b).
Technique	Genotyping
Statistical Method	Genotype data were analyzed using Family Based Association Test (FBAT) software.
Result Summary	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.

SNPs reported by this study for BD (count: 28)

SNP	Related Gene(s)	Allele Change	Statistical Values	Author Comments	Result Category
rs6718289	EGR4 RNU6-111P		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4872533	EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4535741	EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4520160	EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs7729723	EGR1		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs6914	EGR1		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs6747506	EGR4 RNU6-111P		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs10095121	EGR3	C/T	Association analysis: FBAT, chi square=4.83, P-value = 0.028	Significant association was observed in BPI. Significant association was observed in BPI.	Positive
rs10104039	EGR3	C/T	Association analysis: FBAT, chi square=4.90, P-value = 0.027	Significant association was observed in BPI. Significant association was observed in BPI.	Positive
rs10128333	EGR2 ADO		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11741807	EGR1		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1008949	EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs17088536	EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1548587	EGR1		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1996147	EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1800778	EGR1		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11775096	PEBP4 EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs11743810	EGR1		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1522928	EGR4 RNU6-111P		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs1509963	EGR2 ADO		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs3750192	EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2297488	EGR2		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs4295666	EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs3813224	EGR4		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2090052	EGR3		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2051861	EGR1		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2295814	EGR2 ADO		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs2229294	EGR4		Association analysis: FBAT, P-value > 0.05	No significant association was observed in BD. No significant association was observed in BD.	Negative

Haplotypes reported by this study for BD (count: 4)

Markers	Haplotype	Related Gene(s)/Region(s)	Statistical Values	Author Comments	Result Category
rs10095121 - rs10104039	T-C	EGR3	Family-Based Haplotype Test:chi square=4.95, P-value = 0.026	Significant association was observed in BPI. Significant association was observed in BPI.	Positive
rs10095121 - rs10104039	C-T	EGR3	Family-Based Haplotype Test:chi square=6.06, P-value = 0.014	Significant association was observed in BPI. Significant association was observed in BPI.	Positive
rs10095121 - rs10104039	T-T	EGR3	Family-Based Haplotype Test:chi square=0, P-value = 0.966	No significant association was observed in BD. No significant association was observed in BD.	Negative
rs10095121 - rs10104039	C-C	EGR3	Family-Based Haplotype Test:chi square=0.75, P-value = 0.387	No significant association was observed in BD. No significant association was observed in BD.	Negative

Genes reported by this study for BD (count: 4)

Gene	Statistical Values/Author Comments	Result Category
EGR1	None of the SNPs tested in EGR1 was associated with child BP-I. None of the SNPs tested in EGR1 was associated with child BP-I.	Negative
EGR3	Our study revealed a preliminary finding suggesting that EGR3, a gene that translates environmental ...... 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. More...	Positive
EGR4	None of the SNPs tested in EGR4 was associated with child BP-I. None of the SNPs tested in EGR4 was associated with child BP-I.	Negative
EGR2	None of the SNPs tested in EGR2 was associated with child BP-I. None of the SNPs tested in EGR2 was associated with child BP-I.	Negative