title: Evidence of sex-modulated association of ZNF804A with schizophrenia.
abstract: BACKGROUND
  The single nucleotide polymorphism (SNP) rs1344706 in ZNF804A (2q32.1) has been associated with schizophrenia in a genome-wide association study (GWAS). A recent candidate gene study, which replicated the positive association with rs1344706, identified another positive SNP (rs7597593) in ZNF804A associated with schizophrenia.
  
  
  METHODS
  We performed an association study of rs7597593 in four GWAS cohorts of European ancestry. Postmortem human brain expression data of normal Caucasian individuals (n = 89) was also analyzed for examining the effect of rs7597593 on ZNF804A messenger RNA expression, using logistic regression and linear regression.
  
  
  RESULTS
  We found that rs7597593 was significantly associated with schizophrenia in the combined GWAS datasets (n = 5023, odds ratio [OR](combined) = 1.15, p = .0011). Analysis of stratification by sex showed that the association was driven by the female subjects (OR = 1.29, p = .0002) and was not significant in male subjects (OR = 1.08, p = .148) in the combined sample of four cohorts. A sex by genotype interaction was near significant in both the Genetic Association Information Network sample (p = .0532) and the combined sample of four cohorts (p(combined) = .0531). Gene expression analysis showed no main effects but a significant female-specific association (p(female) = .047, p(male) = .335) and sex by genotype interaction (p = .0166) for rs7597593.
  
  
  CONCLUSIONS
  Our data suggest a clinical and molecular modulation by sex of the association of ZNF804A SNP rs7597593 and risk of schizophrenia.
authors.affiliation: Genes, Cognition and Psychosis Program and Clinical, Brain Disorders Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Fengyu
authors.initials: F
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Tianzhang
authors.initials: T
authors.lastname: Ye
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Lipska
authors.forename: Richard E
authors.initials: RE
authors.lastname: Straub
authors.forename: Radhakrishna
authors.initials: R
authors.lastname: Vakkalanka
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: David
authors.initials: D
authors.lastname: St Clair
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Hyde
authors.forename: Llewellyn
authors.initials: L
authors.lastname: Bigelow
authors.forename: Joel E
authors.initials: JE
authors.lastname: Kleinman
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016009:Chi-Square Distribution; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D012727:Sex Characteristics; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D051741:Kruppel-Like Transcription Factors; D012333:RNA, Messenger; C540527:ZNF804A protein, human