Genome-wide association study of schizophrenia in a Japanese population

Masashi Ikeda, Branko Aleksic, Yoko Kinoshita, Tomo Okochi, Kunihiro Kawashima, Itaru Kushima, Yoshihito Ito, Yukako Nakamura, Taro Kishi, Takenori Okumura, Yasuhisa Fukuo, Hywel J. Williams, Marian L. Hamshere, Dobril Ivanov, Toshiya Inada, Michio Suzuki, Ryota Hashimoto, Hiroshi Ujike, Masatoshi Takeda, Nick CraddockKozo Kaibuchi, Michael J. Owen, Norio Ozaki, Michael C. O'Donovan, Nakao Iwata

Research output: Contribution to journalArticle

119 Citations (Scopus)

Abstract

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 × 10 -6) or in the complete data set in which the best supported locus was SULT6B1 (rs11895771: p = 3.7 × 10-5 in the meta-analysis). Of loci previously supported by genome-wide association studies, we obtained in the Japanese support for NOTCH4 (rs2071287: pmeta = 5.1 × 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 JapanUK analysis of schizophrenia also revealed a significant correlation (best p = 7.0 × 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.

Original languageEnglish
Pages (from-to)472-478
Number of pages7
JournalBiological Psychiatry
Volume69
Issue number5
DOIs
Publication statusPublished - 01-03-2011

Fingerprint

Genome-Wide Association Study
Schizophrenia
Population
Alleles
Observation
Meta-Analysis
Genome
Genes

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

Cite this

Ikeda, Masashi ; Aleksic, Branko ; Kinoshita, Yoko ; Okochi, Tomo ; Kawashima, Kunihiro ; Kushima, Itaru ; Ito, Yoshihito ; Nakamura, Yukako ; Kishi, Taro ; Okumura, Takenori ; Fukuo, Yasuhisa ; Williams, Hywel J. ; Hamshere, Marian L. ; Ivanov, Dobril ; Inada, Toshiya ; Suzuki, Michio ; Hashimoto, Ryota ; Ujike, Hiroshi ; Takeda, Masatoshi ; Craddock, Nick ; Kaibuchi, Kozo ; Owen, Michael J. ; Ozaki, Norio ; O'Donovan, Michael C. ; Iwata, Nakao. / Genome-wide association study of schizophrenia in a Japanese population. In: Biological Psychiatry. 2011 ; Vol. 69, No. 5. pp. 472-478.
@article{fb55092d542c4e5b8933ea25cee05b5d,
title = "Genome-wide association study of schizophrenia in a Japanese population",
abstract = "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 × 10 -6) or in the complete data set in which the best supported locus was SULT6B1 (rs11895771: p = 3.7 × 10-5 in the meta-analysis). Of loci previously supported by genome-wide association studies, we obtained in the Japanese support for NOTCH4 (rs2071287: pmeta = 5.1 × 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 JapanUK analysis of schizophrenia also revealed a significant correlation (best p = 7.0 × 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.",
author = "Masashi Ikeda and Branko Aleksic and Yoko Kinoshita and Tomo Okochi and Kunihiro Kawashima and Itaru Kushima and Yoshihito Ito and Yukako Nakamura and Taro Kishi and Takenori Okumura and Yasuhisa Fukuo and Williams, {Hywel J.} and Hamshere, {Marian L.} and Dobril Ivanov and Toshiya Inada and Michio Suzuki and Ryota Hashimoto and Hiroshi Ujike and Masatoshi Takeda and Nick Craddock and Kozo Kaibuchi and Owen, {Michael J.} and Norio Ozaki and O'Donovan, {Michael C.} and Nakao Iwata",
year = "2011",
month = "3",
day = "1",
doi = "10.1016/j.biopsych.2010.07.010",
language = "English",
volume = "69",
pages = "472--478",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "5",

}

Ikeda, M, Aleksic, B, Kinoshita, Y, Okochi, T, Kawashima, K, Kushima, I, Ito, Y, Nakamura, Y, Kishi, T, Okumura, T, Fukuo, Y, Williams, HJ, Hamshere, ML, Ivanov, D, Inada, T, Suzuki, M, Hashimoto, R, Ujike, H, Takeda, M, Craddock, N, Kaibuchi, K, Owen, MJ, Ozaki, N, O'Donovan, MC & Iwata, N 2011, 'Genome-wide association study of schizophrenia in a Japanese population', Biological Psychiatry, vol. 69, no. 5, pp. 472-478. https://doi.org/10.1016/j.biopsych.2010.07.010

Genome-wide association study of schizophrenia in a Japanese population. / Ikeda, Masashi; Aleksic, Branko; Kinoshita, Yoko; Okochi, Tomo; Kawashima, Kunihiro; Kushima, Itaru; Ito, Yoshihito; Nakamura, Yukako; Kishi, Taro; Okumura, Takenori; Fukuo, Yasuhisa; Williams, Hywel J.; Hamshere, Marian L.; Ivanov, Dobril; Inada, Toshiya; Suzuki, Michio; Hashimoto, Ryota; Ujike, Hiroshi; Takeda, Masatoshi; Craddock, Nick; Kaibuchi, Kozo; Owen, Michael J.; Ozaki, Norio; O'Donovan, Michael C.; Iwata, Nakao.

In: Biological Psychiatry, Vol. 69, No. 5, 01.03.2011, p. 472-478.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association study of schizophrenia in a Japanese population

AU - Ikeda, Masashi

AU - Aleksic, Branko

AU - Kinoshita, Yoko

AU - Okochi, Tomo

AU - Kawashima, Kunihiro

AU - Kushima, Itaru

AU - Ito, Yoshihito

AU - Nakamura, Yukako

AU - Kishi, Taro

AU - Okumura, Takenori

AU - Fukuo, Yasuhisa

AU - Williams, Hywel J.

AU - Hamshere, Marian L.

AU - Ivanov, Dobril

AU - Inada, Toshiya

AU - Suzuki, Michio

AU - Hashimoto, Ryota

AU - Ujike, Hiroshi

AU - Takeda, Masatoshi

AU - Craddock, Nick

AU - Kaibuchi, Kozo

AU - Owen, Michael J.

AU - Ozaki, Norio

AU - O'Donovan, Michael C.

AU - Iwata, Nakao

PY - 2011/3/1

Y1 - 2011/3/1

N2 - 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 × 10 -6) or in the complete data set in which the best supported locus was SULT6B1 (rs11895771: p = 3.7 × 10-5 in the meta-analysis). Of loci previously supported by genome-wide association studies, we obtained in the Japanese support for NOTCH4 (rs2071287: pmeta = 5.1 × 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 JapanUK analysis of schizophrenia also revealed a significant correlation (best p = 7.0 × 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.

AB - 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 × 10 -6) or in the complete data set in which the best supported locus was SULT6B1 (rs11895771: p = 3.7 × 10-5 in the meta-analysis). Of loci previously supported by genome-wide association studies, we obtained in the Japanese support for NOTCH4 (rs2071287: pmeta = 5.1 × 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 JapanUK analysis of schizophrenia also revealed a significant correlation (best p = 7.0 × 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.

UR - http://www.scopus.com/inward/record.url?scp=79951681574&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951681574&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2010.07.010

DO - 10.1016/j.biopsych.2010.07.010

M3 - Article

C2 - 20832056

AN - SCOPUS:79951681574

VL - 69

SP - 472

EP - 478

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 5

ER -