Evidence of sex-modulated association of ZNF804A with schizophrenia

Fengyu Zhang, Qiang Chen, Tianzhang Ye, Barbara K Lipska, Richard E Straub, Radhakrishna Vakkalanka, Dan Rujescu, David St Clair, Thomas M Hyde, Llewellyn Bigelow, Joel E Kleinman, Daniel R Weinberger

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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 (pcombined = .0531). Gene expression analysis showed no main effects but a significant female-specific association (pfemale = .047, pmale = .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.
Original languageEnglish
Pages (from-to)914-917
Number of pages4
JournalBiological Psychiatry
Volume69
Issue number10
Early online date24 Feb 2011
DOIs
Publication statusPublished - 15 May 2011

Fingerprint

Genome-Wide Association Study
Schizophrenia
Single Nucleotide Polymorphism
Odds Ratio
Genotype
Information Services
Linear Models
Logistic Models
Gene Expression
Messenger RNA
Brain
Genes

Keywords

  • gender
  • gene-sex interaction
  • schizophrenia
  • ZNF804A

Cite this

Zhang, F., Chen, Q., Ye, T., Lipska, B. K., Straub, R. E., Vakkalanka, R., ... Weinberger, D. R. (2011). Evidence of sex-modulated association of ZNF804A with schizophrenia. Biological Psychiatry, 69(10), 914-917. https://doi.org/10.1016/j.biopsych.2011.01.003

Evidence of sex-modulated association of ZNF804A with schizophrenia. / Zhang, Fengyu; Chen, Qiang; Ye, Tianzhang; Lipska, Barbara K; Straub, Richard E; Vakkalanka, Radhakrishna; Rujescu, Dan; St Clair, David; Hyde, Thomas M; Bigelow, Llewellyn; Kleinman, Joel E; Weinberger, Daniel R.

In: Biological Psychiatry, Vol. 69, No. 10, 15.05.2011, p. 914-917.

Research output: Contribution to journalArticle

Zhang, F, Chen, Q, Ye, T, Lipska, BK, Straub, RE, Vakkalanka, R, Rujescu, D, St Clair, D, Hyde, TM, Bigelow, L, Kleinman, JE & Weinberger, DR 2011, 'Evidence of sex-modulated association of ZNF804A with schizophrenia' Biological Psychiatry, vol. 69, no. 10, pp. 914-917. https://doi.org/10.1016/j.biopsych.2011.01.003
Zhang F, Chen Q, Ye T, Lipska BK, Straub RE, Vakkalanka R et al. Evidence of sex-modulated association of ZNF804A with schizophrenia. Biological Psychiatry. 2011 May 15;69(10):914-917. https://doi.org/10.1016/j.biopsych.2011.01.003
Zhang, Fengyu ; Chen, Qiang ; Ye, Tianzhang ; Lipska, Barbara K ; Straub, Richard E ; Vakkalanka, Radhakrishna ; Rujescu, Dan ; St Clair, David ; Hyde, Thomas M ; Bigelow, Llewellyn ; Kleinman, Joel E ; Weinberger, Daniel R. / Evidence of sex-modulated association of ZNF804A with schizophrenia. In: Biological Psychiatry. 2011 ; Vol. 69, No. 10. pp. 914-917.
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title = "Evidence of sex-modulated association of ZNF804A with schizophrenia",
abstract = "BackgroundThe 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.MethodsWe 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.ResultsWe 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 (pcombined = .0531). Gene expression analysis showed no main effects but a significant female-specific association (pfemale = .047, pmale = .335) and sex by genotype interaction (p = .0166) for rs7597593.ConclusionsOur data suggest a clinical and molecular modulation by sex of the association of ZNF804A SNP rs7597593 and risk of schizophrenia.",
keywords = "gender, gene-sex interaction , schizophrenia, ZNF804A",
author = "Fengyu Zhang and Qiang Chen and Tianzhang Ye and Lipska, {Barbara K} and Straub, {Richard E} and Radhakrishna Vakkalanka and Dan Rujescu and {St Clair}, David and Hyde, {Thomas M} and Llewellyn Bigelow and Kleinman, {Joel E} and Weinberger, {Daniel R}",
note = "Copyright {\circledC} 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.",
year = "2011",
month = "5",
day = "15",
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pages = "914--917",
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TY - JOUR

T1 - Evidence of sex-modulated association of ZNF804A with schizophrenia

AU - Zhang, Fengyu

AU - Chen, Qiang

AU - Ye, Tianzhang

AU - Lipska, Barbara K

AU - Straub, Richard E

AU - Vakkalanka, Radhakrishna

AU - Rujescu, Dan

AU - St Clair, David

AU - Hyde, Thomas M

AU - Bigelow, Llewellyn

AU - Kleinman, Joel E

AU - Weinberger, Daniel R

N1 - Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2011/5/15

Y1 - 2011/5/15

N2 - BackgroundThe 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.MethodsWe 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.ResultsWe 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 (pcombined = .0531). Gene expression analysis showed no main effects but a significant female-specific association (pfemale = .047, pmale = .335) and sex by genotype interaction (p = .0166) for rs7597593.ConclusionsOur data suggest a clinical and molecular modulation by sex of the association of ZNF804A SNP rs7597593 and risk of schizophrenia.

AB - BackgroundThe 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.MethodsWe 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.ResultsWe 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 (pcombined = .0531). Gene expression analysis showed no main effects but a significant female-specific association (pfemale = .047, pmale = .335) and sex by genotype interaction (p = .0166) for rs7597593.ConclusionsOur data suggest a clinical and molecular modulation by sex of the association of ZNF804A SNP rs7597593 and risk of schizophrenia.

KW - gender

KW - gene-sex interaction

KW - schizophrenia

KW - ZNF804A

U2 - 10.1016/j.biopsych.2011.01.003

DO - 10.1016/j.biopsych.2011.01.003

M3 - Article

VL - 69

SP - 914

EP - 917

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 10

ER -