Replication and cross-phenotype study based upon schizophrenia GWASs data in the Japanese population: Support for association of MHC region with psychosis

Takeo Saito, Kenji Kondo, Yoshimi Iwayama, Ayu Shimasaki, Branko Aleksic, Kazuo Yamada, Tomoko Toyota, Eiji Hattori, Kosei Esaki, Hiroshi Ujike, Toshiya Inada, Hiroshi Kunugi, Tadafumi Kato, Takeo Yoshikawa, Norio Ozaki, Masashi Ikeda, Nakao Iwata

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Abstract

Recent genome-wide association studies (GWASs) of schizophrenia (SCZ) identified several susceptibility genes and suggested shared genetic components between SCZ and bipolar disorder (BD). We conducted a genetic association study of single nucleotide polymorphisms (SNPs) selected according to previous SCZ GWAS targeting psychotic disorders (SCZ and BD) in the Japanese population. Fifty-one SNPs were analyzed in a two-stage design using first-set screening samples (all SNPs: 1,032 SCZ, 1,012 BD, and 993 controls) and second-set replication samples ("significant" SNPs in the first-set screening analysis: 1,808 SCZ, 821 BD, and 2,321 controls). We assessed allelic associations between the selected SNPs and the three phenotypes (SCZ, BD, and "psychosis" [SCZ+BD]). Nine SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05), of which two SNPs located in the major histocompatibility complex region (rs7759855 in zinc finger and SCAN domain containing 31 [ZSCAN31] and rs1736913 in HLA-F antisense RNA1 [HLA-F-AS1]) were further assessed in the second-set replication samples. The associations were confirmed for rs7759855 (Pcorrected=0.026 for psychosis; Pcorrected=0.032 for SCZ), although the direction of effect was opposite to that in the original GWAS of the Chinese population. Finally, a meta-analysis was conducted using our two samples and using our data and data from Psychiatric GWAS Consortium (PGC), which have shown the same direction of effect. SNP in ZSCAN31 (rs7759855) had the strongest association with the phenotypes (best P=6.8×10-5 for psychosis: present plus PGC results). These data support shared risk SNPs between SCZ and BD in the Japanese population and association between MHC and psychosis.

Original languageEnglish
Pages (from-to)421-427
Number of pages7
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume165
Issue number5
DOIs
Publication statusPublished - 01-01-2014

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Genome-Wide Association Study
Psychotic Disorders
Single Nucleotide Polymorphism
Schizophrenia
Phenotype
Bipolar Disorder
Population
Zinc Fingers
Psychiatry
Genetic Association Studies
Major Histocompatibility Complex
Meta-Analysis

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Saito, Takeo ; Kondo, Kenji ; Iwayama, Yoshimi ; Shimasaki, Ayu ; Aleksic, Branko ; Yamada, Kazuo ; Toyota, Tomoko ; Hattori, Eiji ; Esaki, Kosei ; Ujike, Hiroshi ; Inada, Toshiya ; Kunugi, Hiroshi ; Kato, Tadafumi ; Yoshikawa, Takeo ; Ozaki, Norio ; Ikeda, Masashi ; Iwata, Nakao. / Replication and cross-phenotype study based upon schizophrenia GWASs data in the Japanese population : Support for association of MHC region with psychosis. In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. 2014 ; Vol. 165, No. 5. pp. 421-427.
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abstract = "Recent genome-wide association studies (GWASs) of schizophrenia (SCZ) identified several susceptibility genes and suggested shared genetic components between SCZ and bipolar disorder (BD). We conducted a genetic association study of single nucleotide polymorphisms (SNPs) selected according to previous SCZ GWAS targeting psychotic disorders (SCZ and BD) in the Japanese population. Fifty-one SNPs were analyzed in a two-stage design using first-set screening samples (all SNPs: 1,032 SCZ, 1,012 BD, and 993 controls) and second-set replication samples ({"}significant{"} SNPs in the first-set screening analysis: 1,808 SCZ, 821 BD, and 2,321 controls). We assessed allelic associations between the selected SNPs and the three phenotypes (SCZ, BD, and {"}psychosis{"} [SCZ+BD]). Nine SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05), of which two SNPs located in the major histocompatibility complex region (rs7759855 in zinc finger and SCAN domain containing 31 [ZSCAN31] and rs1736913 in HLA-F antisense RNA1 [HLA-F-AS1]) were further assessed in the second-set replication samples. The associations were confirmed for rs7759855 (Pcorrected=0.026 for psychosis; Pcorrected=0.032 for SCZ), although the direction of effect was opposite to that in the original GWAS of the Chinese population. Finally, a meta-analysis was conducted using our two samples and using our data and data from Psychiatric GWAS Consortium (PGC), which have shown the same direction of effect. SNP in ZSCAN31 (rs7759855) had the strongest association with the phenotypes (best P=6.8×10-5 for psychosis: present plus PGC results). These data support shared risk SNPs between SCZ and BD in the Japanese population and association between MHC and psychosis.",
author = "Takeo Saito and Kenji Kondo and Yoshimi Iwayama and Ayu Shimasaki and Branko Aleksic and Kazuo Yamada and Tomoko Toyota and Eiji Hattori and Kosei Esaki and Hiroshi Ujike and Toshiya Inada and Hiroshi Kunugi and Tadafumi Kato and Takeo Yoshikawa and Norio Ozaki and Masashi Ikeda and Nakao Iwata",
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Saito, T, Kondo, K, Iwayama, Y, Shimasaki, A, Aleksic, B, Yamada, K, Toyota, T, Hattori, E, Esaki, K, Ujike, H, Inada, T, Kunugi, H, Kato, T, Yoshikawa, T, Ozaki, N, Ikeda, M & Iwata, N 2014, 'Replication and cross-phenotype study based upon schizophrenia GWASs data in the Japanese population: Support for association of MHC region with psychosis', American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, vol. 165, no. 5, pp. 421-427. https://doi.org/10.1002/ajmg.b.32246

Replication and cross-phenotype study based upon schizophrenia GWASs data in the Japanese population : Support for association of MHC region with psychosis. / Saito, Takeo; Kondo, Kenji; Iwayama, Yoshimi; Shimasaki, Ayu; Aleksic, Branko; Yamada, Kazuo; Toyota, Tomoko; Hattori, Eiji; Esaki, Kosei; Ujike, Hiroshi; Inada, Toshiya; Kunugi, Hiroshi; Kato, Tadafumi; Yoshikawa, Takeo; Ozaki, Norio; Ikeda, Masashi; Iwata, Nakao.

In: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, Vol. 165, No. 5, 01.01.2014, p. 421-427.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Replication and cross-phenotype study based upon schizophrenia GWASs data in the Japanese population

T2 - Support for association of MHC region with psychosis

AU - Saito, Takeo

AU - Kondo, Kenji

AU - Iwayama, Yoshimi

AU - Shimasaki, Ayu

AU - Aleksic, Branko

AU - Yamada, Kazuo

AU - Toyota, Tomoko

AU - Hattori, Eiji

AU - Esaki, Kosei

AU - Ujike, Hiroshi

AU - Inada, Toshiya

AU - Kunugi, Hiroshi

AU - Kato, Tadafumi

AU - Yoshikawa, Takeo

AU - Ozaki, Norio

AU - Ikeda, Masashi

AU - Iwata, Nakao

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Recent genome-wide association studies (GWASs) of schizophrenia (SCZ) identified several susceptibility genes and suggested shared genetic components between SCZ and bipolar disorder (BD). We conducted a genetic association study of single nucleotide polymorphisms (SNPs) selected according to previous SCZ GWAS targeting psychotic disorders (SCZ and BD) in the Japanese population. Fifty-one SNPs were analyzed in a two-stage design using first-set screening samples (all SNPs: 1,032 SCZ, 1,012 BD, and 993 controls) and second-set replication samples ("significant" SNPs in the first-set screening analysis: 1,808 SCZ, 821 BD, and 2,321 controls). We assessed allelic associations between the selected SNPs and the three phenotypes (SCZ, BD, and "psychosis" [SCZ+BD]). Nine SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05), of which two SNPs located in the major histocompatibility complex region (rs7759855 in zinc finger and SCAN domain containing 31 [ZSCAN31] and rs1736913 in HLA-F antisense RNA1 [HLA-F-AS1]) were further assessed in the second-set replication samples. The associations were confirmed for rs7759855 (Pcorrected=0.026 for psychosis; Pcorrected=0.032 for SCZ), although the direction of effect was opposite to that in the original GWAS of the Chinese population. Finally, a meta-analysis was conducted using our two samples and using our data and data from Psychiatric GWAS Consortium (PGC), which have shown the same direction of effect. SNP in ZSCAN31 (rs7759855) had the strongest association with the phenotypes (best P=6.8×10-5 for psychosis: present plus PGC results). These data support shared risk SNPs between SCZ and BD in the Japanese population and association between MHC and psychosis.

AB - Recent genome-wide association studies (GWASs) of schizophrenia (SCZ) identified several susceptibility genes and suggested shared genetic components between SCZ and bipolar disorder (BD). We conducted a genetic association study of single nucleotide polymorphisms (SNPs) selected according to previous SCZ GWAS targeting psychotic disorders (SCZ and BD) in the Japanese population. Fifty-one SNPs were analyzed in a two-stage design using first-set screening samples (all SNPs: 1,032 SCZ, 1,012 BD, and 993 controls) and second-set replication samples ("significant" SNPs in the first-set screening analysis: 1,808 SCZ, 821 BD, and 2,321 controls). We assessed allelic associations between the selected SNPs and the three phenotypes (SCZ, BD, and "psychosis" [SCZ+BD]). Nine SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05), of which two SNPs located in the major histocompatibility complex region (rs7759855 in zinc finger and SCAN domain containing 31 [ZSCAN31] and rs1736913 in HLA-F antisense RNA1 [HLA-F-AS1]) were further assessed in the second-set replication samples. The associations were confirmed for rs7759855 (Pcorrected=0.026 for psychosis; Pcorrected=0.032 for SCZ), although the direction of effect was opposite to that in the original GWAS of the Chinese population. Finally, a meta-analysis was conducted using our two samples and using our data and data from Psychiatric GWAS Consortium (PGC), which have shown the same direction of effect. SNP in ZSCAN31 (rs7759855) had the strongest association with the phenotypes (best P=6.8×10-5 for psychosis: present plus PGC results). These data support shared risk SNPs between SCZ and BD in the Japanese population and association between MHC and psychosis.

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