title: Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples.
abstract: BACKGROUND
  Associations between schizophrenia (SCZ) and polymorphisms at the regulator of G-protein signaling 4 (RGS4) gene have been reported (single nucleotide polymorphisms [SNPs] 1, 4, 7, and 18). Yet, similar to other SCZ candidate genes, studies have been inconsistent with respect to the associated alleles.
  
  
  METHODS
  In an effort to resolve the role for RGS4 in SCZ susceptibility, we undertook a genotype-based meta-analysis using both published and unpublished family-based and case-control samples (total n = 13,807).
  
  
  RESULTS
  The family-based dataset consisted of 10 samples (2160 families). Significant associations with individual SNPs/haplotypes were not observed. In contrast, global analysis revealed significant transmission distortion (p = .0009). Specifically, analyses suggested overtransmission of two common haplotypes that account for the vast majority of all haplotypes. Separate analyses of 3486 cases and 3755 control samples (eight samples) detected a significant association with SNP 4 (p = .01). Individual haplotype analyses were not significant, but evaluation of test statistics from individual samples suggested significant associations.
  
  
  CONCLUSIONS
  Our collaborative meta-analysis represents one of the largest SCZ association studies to date. No individual risk factor arose from our analyses, but interpretation of these results is not straightforward. Our analyses suggest risk due to at least two common haplotypes in the presence of heterogeneity. Similar analysis for other putative susceptibility genes is warranted.
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Talkowski
authors.forename: Howard
authors.initials: H
authors.lastname: Seltman
authors.forename: Anne S
authors.initials: AS
authors.lastname: Bassett
authors.forename: Linda M
authors.initials: LM
authors.lastname: Brzustowicz
authors.forename: Xiangning
authors.initials: X
authors.lastname: Chen
authors.forename: Kodavali V
authors.initials: KV
authors.lastname: Chowdari
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: Quirino
authors.initials: Q
authors.lastname: Cordeiro
authors.forename: Aiden P
authors.initials: AP
authors.lastname: Corvin
authors.forename: Smita N
authors.initials: SN
authors.lastname: Deshpande
authors.forename: Michael F
authors.initials: MF
authors.lastname: Egan
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Kendler
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Heston
authors.forename: Pat
authors.initials: P
authors.lastname: Levitt
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Karoly
authors.initials: K
authors.lastname: Mirnics
authors.forename: Derek W
authors.initials: DW
authors.lastname: Morris
authors.forename: Nadine
authors.initials: N
authors.lastname: Norton
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Christian
authors.initials: C
authors.lastname: Richard
authors.forename: Prachi
authors.initials: P
authors.lastname: Semwal
authors.forename: Janet L
authors.initials: JL
authors.lastname: Sobell
authors.forename: David
authors.initials: D
authors.lastname: St Clair
authors.forename: Richard E
authors.initials: RE
authors.lastname: Straub
authors.forename: B K
authors.initials: BK
authors.lastname: Thelma
authors.forename: Homero
authors.initials: H
authors.lastname: Vallada
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: Nigel M
authors.initials: NM
authors.lastname: Williams
authors.forename: Joel
authors.initials: J
authors.lastname: Wood
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Bernie
authors.initials: B
authors.lastname: Devlin
authors.forename: Vishwajit L
authors.initials: VL
authors.lastname: Nimgaonkar
mesh_terms: D016022:Case-Control Studies; D030541:Databases, Genetic; D005190:Family; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D017594:Publication Bias; D011786:Quality Control; D012559:Schizophrenia / Q000235:genetics*