Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples.
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resolve the role for RGS4 in SCZ susceptibility, we undertook a genotype-based meta-analysis using both published and unpublished family-based and case-control samples (total n = 13,807).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.
Talkowski
Michael E
ME
Department of Human Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Seltman
Howard
H
Bassett
Anne S
AS
Brzustowicz
Linda M
LM
Chen
Xiangning
X
Chowdari
Kodavali V
KV
Collier
David A
DA
Cordeiro
Quirino
Q
Corvin
Aiden P
AP
Deshpande
Smita N
SN
Egan
Michael F
MF
Gill
Michael
M
Kendler
Kenneth S
KS
Kirov
George
G
Heston
Leonard L
LL
Levitt
Pat
P
Lewis
David A
DA
Li
Tao
T
Mirnics
Karoly
K
Morris
Derek W
DW
Norton
Nadine
N
O'Donovan
Michael C
MC
Owen
Michael J
MJ
Richard
Christian
C
Semwal
Prachi
P
Sobell
Janet L
JL
St Clair
David
D
Straub
Richard E
RE
Thelma
B K
BK
Vallada
Homero
H
Weinberger
Daniel R
DR
Williams
Nigel M
NM
Wood
Joel
J
Zhang
Feng
F
Devlin
Bernie
B
Nimgaonkar
Vishwajit L
VL
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*