Associations of ATF4 gene polymorphisms with schizophrenia in male patients

Mei Qu, Fulei Tang, Lifang Wang, Hao Yan, Yonghua Han, Jun Yan, Weihua Yue, Dai Zhang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Activating transcription factor 4 (ATF4) is considered as a positional candidate gene for schizophrenia due to its location at chromosome 22q13, a region linked to schizophrenia. Furthermore, as protein interaction partner of ATF4, disrupted in schizophrenia 1 (DISC1) and its signal pathway implicated in the pathophysiology of schizophrenia have been widely supported by a number of genetic and neurobiological studies. Our aim was to investigate whether ATF4 is associated with schizophrenia in case-control samples of Han Chinese subjects consisting of 352 schizophrenia patients and 357 healthy controls. We detected 18 single nucleotide polymorphisms (SNPs) in ATF4 locus, two of which were analyzed, including one insertion at the putative core promoter region (rs17001266, -/C) and one nonsynonymous variant in exon 1 (rs4894, C/A, Pro22Gln). Allele distributions of two SNPs showed significant associations with schizophrenia in male subjects (respectively, rs17001266: P = 0.021, OR = 1.58, 95% CI = 1.07-2.33; rs4894: P = 0.004, OR = 1.78, 95% CI = 1.19-2.67), but not in female subjects as well as the entire population. Two haplotypes CC and -A constructed of rs17001266-rs4894 also revealed significant associations with schizophrenia in male group (global P = 0.0097). These findings support that ATF4 gene may be involved in susceptibility to schizophrenia with sex-dependent effect in the Chinese Han population and suggest that further functional assays are needed to verify their relevance to the pathogenesis of schizophrenia.

Original languageEnglish (US)
Pages (from-to)732-736
Number of pages5
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume147
Issue number6
DOIs
StatePublished - Sep 5 2008

Fingerprint

Activating Transcription Factor 4
Schizophrenia
Genes
Single Nucleotide Polymorphism
Genetic Promoter Regions
Haplotypes
Population
Exons
Signal Transduction

Keywords

  • Activating transcription factor 4 (ATF4)
  • Genetic association
  • Haplotype

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Associations of ATF4 gene polymorphisms with schizophrenia in male patients. / Qu, Mei; Tang, Fulei; Wang, Lifang; Yan, Hao; Han, Yonghua; Yan, Jun; Yue, Weihua; Zhang, Dai.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 147, No. 6, 05.09.2008, p. 732-736.

Research output: Contribution to journalArticle

Qu, Mei ; Tang, Fulei ; Wang, Lifang ; Yan, Hao ; Han, Yonghua ; Yan, Jun ; Yue, Weihua ; Zhang, Dai. / Associations of ATF4 gene polymorphisms with schizophrenia in male patients. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2008 ; Vol. 147, No. 6. pp. 732-736.
@article{eedb3551c6124c43816667a7f879dd9b,
title = "Associations of ATF4 gene polymorphisms with schizophrenia in male patients",
abstract = "Activating transcription factor 4 (ATF4) is considered as a positional candidate gene for schizophrenia due to its location at chromosome 22q13, a region linked to schizophrenia. Furthermore, as protein interaction partner of ATF4, disrupted in schizophrenia 1 (DISC1) and its signal pathway implicated in the pathophysiology of schizophrenia have been widely supported by a number of genetic and neurobiological studies. Our aim was to investigate whether ATF4 is associated with schizophrenia in case-control samples of Han Chinese subjects consisting of 352 schizophrenia patients and 357 healthy controls. We detected 18 single nucleotide polymorphisms (SNPs) in ATF4 locus, two of which were analyzed, including one insertion at the putative core promoter region (rs17001266, -/C) and one nonsynonymous variant in exon 1 (rs4894, C/A, Pro22Gln). Allele distributions of two SNPs showed significant associations with schizophrenia in male subjects (respectively, rs17001266: P = 0.021, OR = 1.58, 95{\%} CI = 1.07-2.33; rs4894: P = 0.004, OR = 1.78, 95{\%} CI = 1.19-2.67), but not in female subjects as well as the entire population. Two haplotypes CC and -A constructed of rs17001266-rs4894 also revealed significant associations with schizophrenia in male group (global P = 0.0097). These findings support that ATF4 gene may be involved in susceptibility to schizophrenia with sex-dependent effect in the Chinese Han population and suggest that further functional assays are needed to verify their relevance to the pathogenesis of schizophrenia.",
keywords = "Activating transcription factor 4 (ATF4), Genetic association, Haplotype",
author = "Mei Qu and Fulei Tang and Lifang Wang and Hao Yan and Yonghua Han and Jun Yan and Weihua Yue and Dai Zhang",
year = "2008",
month = "9",
day = "5",
doi = "10.1002/ajmg.b.30675",
language = "English (US)",
volume = "147",
pages = "732--736",
journal = "American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Associations of ATF4 gene polymorphisms with schizophrenia in male patients

AU - Qu, Mei

AU - Tang, Fulei

AU - Wang, Lifang

AU - Yan, Hao

AU - Han, Yonghua

AU - Yan, Jun

AU - Yue, Weihua

AU - Zhang, Dai

PY - 2008/9/5

Y1 - 2008/9/5

N2 - Activating transcription factor 4 (ATF4) is considered as a positional candidate gene for schizophrenia due to its location at chromosome 22q13, a region linked to schizophrenia. Furthermore, as protein interaction partner of ATF4, disrupted in schizophrenia 1 (DISC1) and its signal pathway implicated in the pathophysiology of schizophrenia have been widely supported by a number of genetic and neurobiological studies. Our aim was to investigate whether ATF4 is associated with schizophrenia in case-control samples of Han Chinese subjects consisting of 352 schizophrenia patients and 357 healthy controls. We detected 18 single nucleotide polymorphisms (SNPs) in ATF4 locus, two of which were analyzed, including one insertion at the putative core promoter region (rs17001266, -/C) and one nonsynonymous variant in exon 1 (rs4894, C/A, Pro22Gln). Allele distributions of two SNPs showed significant associations with schizophrenia in male subjects (respectively, rs17001266: P = 0.021, OR = 1.58, 95% CI = 1.07-2.33; rs4894: P = 0.004, OR = 1.78, 95% CI = 1.19-2.67), but not in female subjects as well as the entire population. Two haplotypes CC and -A constructed of rs17001266-rs4894 also revealed significant associations with schizophrenia in male group (global P = 0.0097). These findings support that ATF4 gene may be involved in susceptibility to schizophrenia with sex-dependent effect in the Chinese Han population and suggest that further functional assays are needed to verify their relevance to the pathogenesis of schizophrenia.

AB - Activating transcription factor 4 (ATF4) is considered as a positional candidate gene for schizophrenia due to its location at chromosome 22q13, a region linked to schizophrenia. Furthermore, as protein interaction partner of ATF4, disrupted in schizophrenia 1 (DISC1) and its signal pathway implicated in the pathophysiology of schizophrenia have been widely supported by a number of genetic and neurobiological studies. Our aim was to investigate whether ATF4 is associated with schizophrenia in case-control samples of Han Chinese subjects consisting of 352 schizophrenia patients and 357 healthy controls. We detected 18 single nucleotide polymorphisms (SNPs) in ATF4 locus, two of which were analyzed, including one insertion at the putative core promoter region (rs17001266, -/C) and one nonsynonymous variant in exon 1 (rs4894, C/A, Pro22Gln). Allele distributions of two SNPs showed significant associations with schizophrenia in male subjects (respectively, rs17001266: P = 0.021, OR = 1.58, 95% CI = 1.07-2.33; rs4894: P = 0.004, OR = 1.78, 95% CI = 1.19-2.67), but not in female subjects as well as the entire population. Two haplotypes CC and -A constructed of rs17001266-rs4894 also revealed significant associations with schizophrenia in male group (global P = 0.0097). These findings support that ATF4 gene may be involved in susceptibility to schizophrenia with sex-dependent effect in the Chinese Han population and suggest that further functional assays are needed to verify their relevance to the pathogenesis of schizophrenia.

KW - Activating transcription factor 4 (ATF4)

KW - Genetic association

KW - Haplotype

UR - http://www.scopus.com/inward/record.url?scp=51449086380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=51449086380&partnerID=8YFLogxK

U2 - 10.1002/ajmg.b.30675

DO - 10.1002/ajmg.b.30675

M3 - Article

C2 - 18163433

AN - SCOPUS:51449086380

VL - 147

SP - 732

EP - 736

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

SN - 1552-4841

IS - 6

ER -