Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2.
We and others have previously reported linkage to schizophrenia on chromosome 10q25-q26 but, to date, a susceptibility gene in the region has not been identified. We examined data from 3606 single-nucleotide polymorphisms (SNPs) mapping to 10q25-q26 that had been typed in a genome-wide association study (GWAS) of schizophrenia (479 UK cases/2937 controls). SNPs with P<0.01 (n=40) were genotyped in an additional 163 UK cases and those markers that remained nominally significant at P<0.01 (n=22) were genotyped in replication samples from Ireland, Germany and Bulgaria consisting of a total of 1664 cases with schizophrenia and 3541 controls. Only one SNP, rs17101921, was nominally significant after meta-analyses across the replication samples and this was genotyped in an additional six samples from the United States/Australia, Germany, China, Japan, Israel and Sweden (n=5142 cases/6561 controls). Across all replication samples, the allele at rs17101921 that was associated in the GWAS showed evidence for association independent of the original data (OR 1.17 (95% CI 1.06-1.29), P=0.0009). The SNP maps 85 kb from the nearest gene encoding fibroblast growth factor receptor 2 (FGFR2) making this a potential susceptibility gene for schizophrenia.
O'Donovan
M C
MC
Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK. odonovanmc@cf.ac.uk
Norton
N
N
Williams
H
H
Peirce
T
T
Moskvina
V
V
Nikolov
I
I
Hamshere
M
M
Carroll
L
L
Georgieva
L
L
Dwyer
S
S
Holmans
P
P
Marchini
J L
JL
Spencer
C C A
CC
Howie
B
B
Leung
H-T
HT
Giegling
I
I
Hartmann
A M
AM
Möller
H-J
HJ
Morris
D W
DW
Shi
Y
Y
Feng
G
G
Hoffmann
P
P
Propping
P
P
Vasilescu
C
C
Maier
W
W
Rietschel
M
M
Zammit
S
S
Schumacher
J
J
Quinn
E M
EM
Schulze
T G
TG
Iwata
N
N
Ikeda
M
M
Darvasi
A
A
Shifman
S
S
He
L
L
Duan
J
J
Sanders
A R
AR
Levinson
D F
DF
Adolfsson
R
R
Osby
U
U
Terenius
L
L
Jönsson
E G
EG
Cichon
S
S
Nöthen
M M
MM
Gill
M
M
Corvin
A P
AP
Rujescu
D
D
Gejman
P V
PV
Kirov
G
G
Craddock
N
N
Williams
N M
NM
Owen
M J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002879:Chromosomes, Human, Pair 10; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D055815:Young Adult
D051497:Receptor, Fibroblast Growth Factor, Type 2