Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia.
Several previous studies have reported a significant linkage between markers in the alpha 7 nicotinic cholinergic receptor subunit (CHRNA7) gene and either schizophrenia or the P50 sensory gating deficit, a schizophrenia endophenotype. However, CHRFAM7A, a partially duplicated gene 1.6Mb upstream of the CHRNA7 gene, has complicated further genetic analysis. We genotyped 14 polymorphic markers throughout the full-length CHRNA7 gene and the duplicated region in 188 unrelated Han Chinese patients with schizophrenia and 188 controls. The duplicated regions were assessed by genotyping up- and down-stream polymorphic markers in the vicinity of each region and analyzing the linkage disequilibrium (LD) between each pair of markers. No evidence of risk variants for schizophrenia in either the CHRNA7 gene or the partially duplicated region was found in the LD analysis. A significant deviation from the Hardy-Weinberg equilibrium (HWE) was found only in the genotypic distribution of SNP9 (IVS4-1912) in patients (p=0.00829), but not in controls. In conclusion, our LD analysis did not reveal any association between schizophrenia in our Han Chinese population and the CHRNA7 gene or its partially duplicated region. However, we could not exclude the possibility of a weak genetic effect due to the small sample size. Analyses of larger samples and higher-density markers, particularly around SNP9 (IVS4-1912), are still needed.
Iwata
Yasuhide
Y
Division of Psychological Medicine, Institute of Psychiatry, 1 Windsor Walk, Denmark Hill, London, UK. iwata@hama-med.ac.jp
Nakajima
Mizuho
M
Yamada
Kazuo
K
Nakamura
Kazuhiko
K
Sekine
Yoshimoto
Y
Tsuchiya
Kenji J
KJ
Sugihara
Genichi
G
Matsuzaki
Hideo
H
Suda
Shiro
S
Suzuki
Katsuaki
K
Takei
Nori
N
Mori
Norio
N
Iwayama
Yoshimi
Y
Takao
Hitomi
H
Yoshikawa
Takeo
T
Riley
Brien
B
Makoff
Andrew
A
Sham
Pak
P
Chen
Ronald
R
Collier
David
D
D044466:Asian People / Q000208:ethnology; D016009:Chi-Square Distribution; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D011110:Polymorphism, Genetic; D011978:Receptors, Nicotinic / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
C579167:Chrna7 protein, human; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor