title: No significant association of 14 candidate genes with schizophrenia in a large European ancestry sample: implications for psychiatric genetics.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry and Behavioural Sciences, Evanston Northwestern Healthcare Research Institute, Evanston, IL 60201-3137, USA.
authors.forename: Alan R
authors.initials: AR
authors.lastname: Sanders
authors.forename: Jubao
authors.initials: J
authors.lastname: Duan
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Levinson
authors.forename: Jianxin
authors.initials: J
authors.lastname: Shi
authors.forename: Deli
authors.initials: D
authors.lastname: He
authors.forename: Cuiping
authors.initials: C
authors.lastname: Hou
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Burrell
authors.forename: John P
authors.initials: JP
authors.lastname: Rice
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nertney
authors.forename: Ann
authors.initials: A
authors.lastname: Olincy
authors.forename: Pablo
authors.initials: P
authors.lastname: Rozic
authors.forename: Sophia
authors.initials: S
authors.lastname: Vinogradov
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Buccola
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Mowry
authors.forename: Robert
authors.initials: R
authors.lastname: Freedman
authors.forename: Farooq
authors.initials: F
authors.lastname: Amin
authors.forename: Donald W
authors.initials: DW
authors.lastname: Black
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Silverman
authors.forename: William F
authors.initials: WF
authors.lastname: Byerley
authors.forename: Raymond R
authors.initials: RR
authors.lastname: Crowe
authors.forename: C Robert
authors.initials: CR
authors.lastname: Cloninger
authors.forename: Maria
authors.initials: M
authors.lastname: Martinez
authors.forename: Pablo V
authors.initials: PV
authors.lastname: Gejman
mesh_terms: D000293:Adolescent; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000235:genetics / Q000378:metabolism; D011786:Quality Control; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics*
chemical_list: D002394:Catechol O-Methyltransferase