Genome-Wide Association Study of Schizophrenia in a Japanese Population

被引：137

作者：

Ikeda, Masashi ^{[1
,2
]}

Aleksic, Branko ^{[1
,3
,4
]}

Kinoshita, Yoko ^{[1
,4
]}

Okochi, Tomo ^{[1
,4
]}

Kawashima, Kunihiro ^{[1
,4
]}

Kushima, Itaru ^{[1
,3
,4
]}

Ito, Yoshihito ^{[1
,3
,4
]}

Nakamura, Yukako ^{[3
,4
]}

Kishi, Taro ^{[1
,4
]}

Okumura, Takenori ^{[1
,4
]}

Fukuo, Yasuhisa ^{[1
,4
]}

Williams, Hywel J. ^{[2
]}

Hamshere, Marian L. ^{[2
,5
]}

Ivanov, Dobril ^{[2
,5
]}

Inada, Toshiya ^{[6
]}

Suzuki, Michio ^{[4
,7
]}

Hashimoto, Ryota ^{[4
,8
,9
,10
]}

Ujike, Hiroshi ^{[11
]}

Takeda, Masatoshi ^{[4
,8
,9
,10
]}

Craddock, Nick ^{[2
]}

Kaibuchi, Kozo ^{[12
]}

Owen, Michael J. ^{[2
]}

Ozaki, Norio ^{[3
,4
]}

O'Donovan, Michael C. ^{[2
]}

Iwata, Nakao ^{[1
,4
]}

机构：

[1] Fujita Hlth Univ, Dept Psychiat, Sch Med, Aichi 4701192, Japan

[2] Cardiff Univ, Med Res Council, Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol,Sch Med, Cardiff, S Glam, Wales

[3] Nagoya Univ, Dept Psychiat, Grad Sch Med, Nagoya, Aichi 4648601, Japan

[4] Japan Sci & Technol Agcy, Kawaguchi, Saitama, Japan

[5] Cardiff Univ, Biostat & Bioinformat Unit, Sch Med, Cardiff, S Glam, Wales

[6] Seiwa Hosp, Inst Neuropsychiat, Tokyo, Japan

[7] Toyama Univ, Dept Neuropsychiat, Grad Sch Med, Toyama 930, Japan

[8] Osaka Univ, Dept Psychiat, Grad Sch Med, Osaka, Japan

[9] Kanazawa Univ, Osaka Univ, Mol Res Ctr Childrens Mental Dev, United Grad Sch Child Dev, Osaka, Japan

[10] Hamamatsu Univ Sch Med, Osaka, Japan

[11] Okayama Univ, Dept Neuropsychiat, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan

[12] Nagoya Univ, Grad Sch Med, Dept Cell Pharmacol, Nagoya, Aichi 4648601, Japan

来源：

BIOLOGICAL PSYCHIATRY | 2011年 / 69卷 / 05期

基金：

英国惠康基金; 日本学术振兴会; 英国医学研究理事会;

关键词：

Genome-wide association study; NOTCH4; polygenic component; schizophrenia; SULT6B1; COMMON VARIANTS; PSYCHOSIS; GENETICS; ESTROGEN; LINKAGE; LOCUS;

D O I：

10.1016/j.biopsych.2010.07.010

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Background: Genome-wide association studies have detected a small number of weak but strongly supported schizophrenia risk alleles. Moreover, a substantial polygenic component to the disorder consisting of a large number of such alleles has been reported by the International Schizophrenia Consortium. Method: We report a Japanese genome-wide association study of schizophrenia comprising 575 cases and 564 controls. We attempted to replicate 97 markers, representing a nonredundant panel of markers derived mainly from the top 150 findings, in up to three data sets totaling 1990 cases and 5389 controls. We then attempted to replicate the observation of a polygenic component to the disorder in the Japanese and to determine whether this overlaps that seen in UK populations. Results: Single-locus analysis did not reveal genome-wide support for any locus in the genome-wide association study sample (best p = 6.2 x 10(-6)) or in the complete data set in which the best supported locus was SULT6B1 (rs11895771: p = 3.7 x 10(-5) in the meta-analysis). Of loci previously supported by genome-wide association studies, we obtained in the Japanese support for NOTCH4 (rs2071287: p(meta) = 5.1 x 10(-5)). Using the approach reported by the International Schizophrenia Consortium, we replicated the observation of a polygenic component to schizophrenia within the Japanese population (p = .005). Our trans Japan-UK analysis of schizophrenia also revealed a significant correlation (best p = 7.0 x 10(-5)) in the polygenic component across populations. Conclusions: These results indicate a shared polygenic risk of schizophrenia between Japanese and Caucasian samples, although we did not detect unequivocal evidence for a novel susceptibility gene for schizophrenia.

引用

页码：472 / 478

页数：7

共 26 条

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