Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.
The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.
Arinami
Tadao
T
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki-ken, 305-8577, Japan. tarinami@md.tsukuba.ac.jp
Ohtsuki
Tsuyuka
T
Ishiguro
Hiroki
H
Ujike
Hiroshi
H
Tanaka
Yuji
Y
Morita
Yukitaka
Y
Mineta
Mari
M
Takeichi
Masashi
M
Yamada
Shigeto
S
Imamura
Akira
A
Ohara
Koichi
K
Shibuya
Haruo
H
Ohara
Kenshiro
K
Suzuki
Yasuo
Y
Muratake
Tatsuyuki
T
Kaneko
Naoshi
N
Someya
Toshiyuki
T
Inada
Toshiya
T
Yoshikawa
Takeo
T
Toyota
Tomoko
T
Yamada
Kazuo
K
Kojima
Takuya
T
Takahashi
Sakae
S
Osamu
Ohmori
O
Shinkai
Takahiro
T
Nakamura
Michiko
M
Fukuzako
Hiroshi
H
Hashiguchi
Tomo
T
Niwa
Shin-ich
SI
Ueno
Takuya
T
Tachikawa
Hirokazu
H
Hori
Takafumi
T
Asada
Takashi
T
Nanko
Shinichiro
S
Kunugi
Hiroshi
H
Hashimoto
Ryota
R
Ozaki
Norio
N
Iwata
Nakao
N
Harano
Mutsuo
M
Arai
Heii
H
Ohnuma
Tohru
T
Kusumi
Ichiro
I
Koyama
Tsukasa
T
Yoneda
Hiroshi
H
Fukumaki
Yasuyuki
Y
Shibata
Hiroki
H
Kaneko
Sunao
S
Higuchi
Hisashi
H
Yasui-Furukori
Norio
N
Numachi
Yohtaro
Y
Itokawa
Masanari
M
Okazaki
Yuji
Y
D002878:Chromosomes, Human, Pair 1; D002883:Chromosomes, Human, Pair 14; D002890:Chromosomes, Human, Pair 20; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008126:Lod Score; D018895:Microsatellite Repeats; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D035781:Siblings
D005819:Genetic Markers