title: Polymorphisms in seizure 6-like gene are associated with bipolar disorder I: evidence of gene × gender interaction.
abstract: BACKGROUND
  Previous reports have suggested that there may be gene × gender interaction for bipolar disorder (BD)-associated genes/loci at 22q11-13. This study aimed to investigate the associations of SEZ6L genetic variants with bipolar disorder I (BD-I) and to examine gender-specific genetic associations.
  
  
  METHODS
  605 BD-I Caucasian cases and 1034 controls were selected from the publicly available data of the Whole Genome Association Study of BD. To increase power, an additional 362 Caucasian controls were added to this study from the Genome-Wide Association Study of Schizophrenia. In total, 605 BD-I cases and 1396 controls (934 males and 1067 females) were available for genetic association analysis of 118 SNPs within the SEZ6L gene using PLINK software.
  
  
  RESULTS
  16 SNPs showed significant gene x gender interactions influencing BD-I (P<0.01). In addition, significant differences in the distribution of the alleles for these 16 SNPs were observed between the female BD-I patients and healthy controls (P<0.015) but no significant associations were found for the male sample (P>0.05). The SNP rs4822691 showed the strongest association with BD-I in the female sample (P=2.18 × 10(-4)) and the strongest gene × gender interaction in influencing BD-I (P=9.16 × 10(-5)).
  
  
  CONCLUSIONS
  The findings of this study need to be replicated in independent samples.
  
  
  CONCLUSIONS
  This is the first demonstration that genetic variants in the SEZ6L gene are associated with BD-I in female patients and provides additional compelling evidence for genetic variation at 22q11-13 that influences BD-I risk. The present findings highlight the gene x gender interactions modifying BD-I susceptibility.
authors.affiliation: Departments of Psychiatry and Neurology Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, and The Center of Excellence in Neuroscience, El Paso, Texas, USA. chun.xu@ttuhsc.edu
authors.forename: Chun
authors.initials: C
authors.lastname: Xu
authors.forename: Jerald E
authors.initials: JE
authors.lastname: Mullersman
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Brenda
authors.initials: B
authors.lastname: Bin Su
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Mao
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Posada
authors.forename: Cynthia
authors.initials: C
authors.lastname: Camarillo
authors.forename: Yu
authors.initials: Y
authors.lastname: Mao
authors.forename: Michael A
authors.initials: MA
authors.lastname: Escamilla
authors.forename: Ke-Sheng
authors.initials: KS
authors.lastname: Wang
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D004843:Epistasis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D044465:White People / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C421964:SEZ6L protein, human