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.
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: Ilaria Guella; Adolfo Sequeira; Brandi Rollins; Ling Morgan; Richard M Myers; Stanley J Watson; Huda Akil; William E Bunney; Lynn E Delisi; William Byerley; Marquis P Vawter Journal: Schizophr Res Date: 2013-12-07 Impact factor: 4.939
Authors: D B Hancock; J L Levy; N C Gaddis; C Glasheen; N L Saccone; G P Page; L J Bierut; A H Kral; E O Johnson Journal: Genes Brain Behav Date: 2015-10-20 Impact factor: 3.449
Authors: Ran Tao; Helena Cousijn; Andrew E Jaffe; Philip W J Burnet; Freya Edwards; Sharon L Eastwood; Joo Heon Shin; Tracy A Lane; Mary A Walker; Brady J Maher; Daniel R Weinberger; Paul J Harrison; Thomas M Hyde; Joel E Kleinman Journal: JAMA Psychiatry Date: 2014-10 Impact factor: 21.596
Authors: Thomas H Wassink; Eric A Epping; Danielle Rudd; Michael Axelsen; Stephen Ziebell; Frank W Fleming; Eric Monson; Beng Choon Ho; Nancy C Andreasen Journal: Arch Gen Psychiatry Date: 2012-09