No significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample: Implications for Psychiatric Genetics

Sanders, Alan R, Duan, Jubao, Levinson, Douglas F, Jianxin, Shi, He, Deli, Hou, Cuiping, Burrell, Gregory J, Rice, John P, Nertney, Deborah A, Olincy, Ann, Rozic, Pablo, Vinogradov, Sophia, Buccola, Nancy, G and Mowry, Bryan (2008) No significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample: Implications for Psychiatric Genetics. American Journal of Psychiatry, 165 4: 497-506. doi:10.1176/appi.ajp.2007.07101573


Author Sanders, Alan R
Duan, Jubao
Levinson, Douglas F
Jianxin, Shi
He, Deli
Hou, Cuiping
Burrell, Gregory J
Rice, John P
Nertney, Deborah A
Olincy, Ann
Rozic, Pablo
Vinogradov, Sophia
Buccola, Nancy, G
Mowry, Bryan
Title No significant Association of 14 Candidate Genes With Schizophrenia in a Large European Ancestry Sample: Implications for Psychiatric Genetics
Journal name American Journal of Psychiatry   Check publisher's open access policy
ISSN 0002-953X
Publication date 2008-04-01
Sub-type Article (original research)
DOI 10.1176/appi.ajp.2007.07101573
Open Access Status Not Open Access
Volume 165
Issue 4
Start page 497
End page 506
Total pages 10
Editor Dr Nancy C Andreasen
Sandra L Patterson
Place of publication United States
Publisher American Psychiatric Publishing Inc
Language eng
Subject 321204 Mental Health
C1
920209 Mental Health Services
111714 Mental Health
Abstract Objective: The authors carried out a genetic association study of 14 schizophrenia candidate genes (RGS4, DISC1, DTNBP1, STX7, TAAR6, PPP3CC, NRG1, DRD2, HTR2A, DAOA, AKT1, CHRNA7, COMT, and ARVCF). This study tested the hypothesis of association of schizophrenia with common single nucleotide polymorphisms (SNPs) in these genes using the largest sample to date that has been collected with uniform clinical methods and the most comprehensive set of SNPs in each gene. Method: The sample included 1,870 cases (schizophrenia and schizoaffective disorder) and 2,002 screened comparison subjects (i.e. controls), all of European ancestry, with ancestral outliers excluded based on analysis of ancestry-informative markers. The authors genotyped 789 SNPs, including tags for most common SNPs in each gene, SNPs previously reported as associated, and SNPs located in functional domains of genes such as promoters, coding exons (including nonsynonymous SNPs), 3′ untranslated regions, and conserved noncoding sequences. After extensive data cleaning, 648 SNPs were analyzed for association of single SNPs and of haplotypes. Results: Neither experiment-wide nor gene-wide statistical significance was observed in the primary single-SNP analyses or in secondary analyses of haplotypes or of imputed genotypes for additional common HapMap SNPs. Results in SNPs previously reported as associated with schizophrenia were consistent with chance expectation, and four functional polymorphisms in COMT, DRD2, and HTR2A did not produce nominally significant evidence to support previous evidence for association. Conclusions: It is unlikely that common SNPs in these genes account for a substantial proportion of the genetic risk for schizophrenia, although small effects cannot be ruled out.
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
Excellence in Research Australia (ERA) - Collection
 
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Created: Wed, 01 Apr 2009, 22:03:50 EST by Carmel Meir on behalf of School of Medicine