Testing for genetic association between the ZDHHC8 gene locus and susceptibility to schizophrenia: An integrated analysis of multiple datasets

Mingqing Xu, David Malcolm St Clair, Lin He

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A number of studies have reported an association between the ZDHHC8 gene locus and schizophrenia but have produced some divergent findings and their interpretation is not straightforward. We investigated the association of the ZDHHC8 gene locus with schizophrenia using meta-analytic techniques, combining all published data up to May 2009 and focusing on 10 independent studies from six published references covering 2,894 cases, 2,932 controls and 1,225 parent-offspring trios. We restricted the analysis to studies investigating rs175174, the most frequently studied single nucleotide polymorphism (SNP). Stratified meta-analysis was conducted to investigate whether ancestry, study design, or gender moderated any association. Analyses of linkage disequilibrium (LD) and haplotype structure of this gene locus were also performed based on the hapmap project genotype data to determine whether there were other independent polymorphic markers which might contribute to susceptibility to schizophrenia in particular ethnic populations. We found no allelic- or genotype-wise evidence for an association of the rs175174 SNP with schizophrenia in our overall analysis. After applying stratified analyses, there was only a weak nominal genotype-wise association of this SNP with schizophrenia in the dominant genetic model in East Asian populations (P¿=¿0.049), which might be caused by significant between-study heterogeneity (P¿=¿0.042). No significant publication bias was detected. Other polymorphic markers within this gene genotyped in the hapmap project across different ethnic populations were in strong LD with rs175174. Consistently negative associations were found in the rs175174 polymorphism. LD structure further suggested that the ZDHHC8 locus might not play an important role in the etiology of schizophrenia.
Original languageEnglish
Pages (from-to)1266-1275
Number of pages10
JournalAmerican Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Volume153B
Issue number7
DOIs
Publication statusPublished - 5 Oct 2010

Fingerprint

Genetic Testing
Schizophrenia
Linkage Disequilibrium
HapMap Project
Genes
Single Nucleotide Polymorphism
Genotype
Population
Publication Bias
Genetic Models
Haplotypes
Meta-Analysis
Datasets

Keywords

  • meta-analysis
  • schizophrenia
  • ZDHHC8 gene
  • genetic polymorphism
  • linkage disequilibrium analysis

Cite this

@article{72cfd250107d4ca69d4941132b99f33c,
title = "Testing for genetic association between the ZDHHC8 gene locus and susceptibility to schizophrenia: An integrated analysis of multiple datasets",
abstract = "A number of studies have reported an association between the ZDHHC8 gene locus and schizophrenia but have produced some divergent findings and their interpretation is not straightforward. We investigated the association of the ZDHHC8 gene locus with schizophrenia using meta-analytic techniques, combining all published data up to May 2009 and focusing on 10 independent studies from six published references covering 2,894 cases, 2,932 controls and 1,225 parent-offspring trios. We restricted the analysis to studies investigating rs175174, the most frequently studied single nucleotide polymorphism (SNP). Stratified meta-analysis was conducted to investigate whether ancestry, study design, or gender moderated any association. Analyses of linkage disequilibrium (LD) and haplotype structure of this gene locus were also performed based on the hapmap project genotype data to determine whether there were other independent polymorphic markers which might contribute to susceptibility to schizophrenia in particular ethnic populations. We found no allelic- or genotype-wise evidence for an association of the rs175174 SNP with schizophrenia in our overall analysis. After applying stratified analyses, there was only a weak nominal genotype-wise association of this SNP with schizophrenia in the dominant genetic model in East Asian populations (P¿=¿0.049), which might be caused by significant between-study heterogeneity (P¿=¿0.042). No significant publication bias was detected. Other polymorphic markers within this gene genotyped in the hapmap project across different ethnic populations were in strong LD with rs175174. Consistently negative associations were found in the rs175174 polymorphism. LD structure further suggested that the ZDHHC8 locus might not play an important role in the etiology of schizophrenia.",
keywords = "meta-analysis, schizophrenia, ZDHHC8 gene, genetic polymorphism, linkage disequilibrium analysis",
author = "Mingqing Xu and {St Clair}, {David Malcolm} and Lin He",
year = "2010",
month = "10",
day = "5",
doi = "10.1002/ajmg.b.31096",
language = "English",
volume = "153B",
pages = "1266--1275",
journal = "American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics",
issn = "1552-4841",
publisher = "Wiley",
number = "7",

}

TY - JOUR

T1 - Testing for genetic association between the ZDHHC8 gene locus and susceptibility to schizophrenia

T2 - An integrated analysis of multiple datasets

AU - Xu, Mingqing

AU - St Clair, David Malcolm

AU - He, Lin

PY - 2010/10/5

Y1 - 2010/10/5

N2 - A number of studies have reported an association between the ZDHHC8 gene locus and schizophrenia but have produced some divergent findings and their interpretation is not straightforward. We investigated the association of the ZDHHC8 gene locus with schizophrenia using meta-analytic techniques, combining all published data up to May 2009 and focusing on 10 independent studies from six published references covering 2,894 cases, 2,932 controls and 1,225 parent-offspring trios. We restricted the analysis to studies investigating rs175174, the most frequently studied single nucleotide polymorphism (SNP). Stratified meta-analysis was conducted to investigate whether ancestry, study design, or gender moderated any association. Analyses of linkage disequilibrium (LD) and haplotype structure of this gene locus were also performed based on the hapmap project genotype data to determine whether there were other independent polymorphic markers which might contribute to susceptibility to schizophrenia in particular ethnic populations. We found no allelic- or genotype-wise evidence for an association of the rs175174 SNP with schizophrenia in our overall analysis. After applying stratified analyses, there was only a weak nominal genotype-wise association of this SNP with schizophrenia in the dominant genetic model in East Asian populations (P¿=¿0.049), which might be caused by significant between-study heterogeneity (P¿=¿0.042). No significant publication bias was detected. Other polymorphic markers within this gene genotyped in the hapmap project across different ethnic populations were in strong LD with rs175174. Consistently negative associations were found in the rs175174 polymorphism. LD structure further suggested that the ZDHHC8 locus might not play an important role in the etiology of schizophrenia.

AB - A number of studies have reported an association between the ZDHHC8 gene locus and schizophrenia but have produced some divergent findings and their interpretation is not straightforward. We investigated the association of the ZDHHC8 gene locus with schizophrenia using meta-analytic techniques, combining all published data up to May 2009 and focusing on 10 independent studies from six published references covering 2,894 cases, 2,932 controls and 1,225 parent-offspring trios. We restricted the analysis to studies investigating rs175174, the most frequently studied single nucleotide polymorphism (SNP). Stratified meta-analysis was conducted to investigate whether ancestry, study design, or gender moderated any association. Analyses of linkage disequilibrium (LD) and haplotype structure of this gene locus were also performed based on the hapmap project genotype data to determine whether there were other independent polymorphic markers which might contribute to susceptibility to schizophrenia in particular ethnic populations. We found no allelic- or genotype-wise evidence for an association of the rs175174 SNP with schizophrenia in our overall analysis. After applying stratified analyses, there was only a weak nominal genotype-wise association of this SNP with schizophrenia in the dominant genetic model in East Asian populations (P¿=¿0.049), which might be caused by significant between-study heterogeneity (P¿=¿0.042). No significant publication bias was detected. Other polymorphic markers within this gene genotyped in the hapmap project across different ethnic populations were in strong LD with rs175174. Consistently negative associations were found in the rs175174 polymorphism. LD structure further suggested that the ZDHHC8 locus might not play an important role in the etiology of schizophrenia.

KW - meta-analysis

KW - schizophrenia

KW - ZDHHC8 gene

KW - genetic polymorphism

KW - linkage disequilibrium analysis

U2 - 10.1002/ajmg.b.31096

DO - 10.1002/ajmg.b.31096

M3 - Article

C2 - 20661937

VL - 153B

SP - 1266

EP - 1275

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

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

SN - 1552-4841

IS - 7

ER -