Association of neuregulin 1 with schizophrenia confirmed in a Scottish population.
Recently, we identified neuregulin 1 (NRG1) as a susceptibility gene for schizophrenia in the Icelandic population, by a combined linkage and association approach. Here, we report the first study evaluating the relevance of NRG1 to schizophrenia in a population outside Iceland. Markers representing a core at-risk haplotype found in Icelanders at the 5' end of the NRG1 gene were genotyped in 609 unrelated Scottish patients and 618 unrelated Scottish control individuals. This haplotype consisted of five SNP markers and two microsatellites, which all appear to be in strong linkage disequilibrium. For the Scottish patients and control subjects, haplotype frequencies were estimated by maximum likelihood, using the expectation-maximization algorithm. The frequency of the seven-marker haplotype among the Scottish patients was significantly greater than that among the control subjects (10.2% vs. 5.9%, P=.00031). The estimated risk ratio was 1.8, which is in keeping with our report of unrelated Icelandic patients (2.1). Three of the seven markers in the haplotype gave single-point P values ranging from .000064 to .0021 for the allele contributing to the at-risk haplotype. This direct replication of haplotype association in a second population further implicates NRG1 as a factor that contributes to the etiology of schizophrenia.
Stefansson
Hreinn
H
deCODE Genetics, Reykjavík, Iceland. hreinn@decode.is
Sarginson
Jane
J
Kong
Augustine
A
Yates
Phil
P
Steinthorsdottir
Valgerdur
V
Gudfinnsson
Einar
E
Gunnarsdottir
Steinunn
S
Walker
Nicholas
N
Petursson
Hannes
H
Crombie
Caroline
C
Ingason
Andres
A
Gulcher
Jeffrey R
JR
Stefansson
Kari
K
St Clair
David
D
D000465:Algorithms; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats / Q000235:genetics; D008969:Molecular Sequence Data; D020890:Neuregulin-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000235:genetics*; D012606:Scotland
D005819:Genetic Markers; D020890:Neuregulin-1