title: Family-based association study of early growth response gene 3 with child bipolar I disorder.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 425 N. 5th St., Phoenix, AZ 85004, USA. amelia@email.arizona.edu
authors.forename: Amelia L
authors.initials: AL
authors.lastname: Gallitano
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tillman
authors.forename: Valentin
authors.initials: V
authors.lastname: Dinu
authors.forename: Barbara
authors.initials: B
authors.lastname: Geller
mesh_terms: D000293:Adolescent; D001714:Bipolar Disorder / Q000235:genetics*; D002648:Child; D051776:Early Growth Response Protein 3 / Q000235:genetics*; D051765:Early Growth Response Transcription Factors / Q000235:genetics; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D051765:Early Growth Response Transcription Factors; D051776:Early Growth Response Protein 3