Genetic Variants on 3q21 and in the Sp8 Transcription Factor Gene (SP8) as Susceptibility Loci for Psychotic Disorders: A Genetic Association Study

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

Research output: Contribution to journalArticle

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Abstract

Background:Recent genome-wide association studies (GWASs) investigating bipolar disorder (BD) have detected a number of susceptibility genes. These studies have also provided novel insight into shared genetic components between BD and schizophrenia (SCZ), two major psychotic disorders. To examine the replication of the risk variants for BD and the pleiotropic effect of the variants associated with BD, we conducted a genetic association study of single nucleotide polymorphisms (SNPs) that were selected based upon previous BD GWASs, which targeted psychotic disorders (BD and SCZ) in the Japanese population.Methods:Forty-eight SNPs were selected based upon previous GWASs. A two-stage analysis was conducted using first-set screening (for all SNPs: BD = 1,012, SCZ = 1,032 and control = 993) and second-set replication samples (for significant SNPs in the screening analysis: BD = 821, SCZ = 1,808 and control = 2,149). We assessed allelic association between BD, SCZ, psychosis (BD+SCZ) and the SNPs selected for the analysis.Results:Eight SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05). Among these SNPs, the top two SNPs (associated with psychosis: Pcorrected = 0.048 and 0.037 for rs2251219 and rs2709722, respectively) were further assessed in the second-set samples, and we replicated the signals from the initial screening analysis (associated with psychosis: Pcorrected = 0.0070 and 0.033 for rs2251219 and rs2709722, respectively). The meta-analysis between the current and previous GWAS results showed that rs2251219 in Polybromo1 (PBRM1) was significant on genome-wide association level (P = 5×10-8) only for BD (P = 9.4×10-9) and psychosis (P = 2.0×10-10). Although the association of rs2709722 in Sp8 transcription factor (SP8) was suggestive in the Asian population (P = 2.1×10-7 for psychosis), this signal weakened when the samples size was increased by including data from a Caucasian population (P = 4.3×10-3).Conclusions:We found 3p21.1 (including PBRM1, strong linkage disequilibrium made it difficult to pinpoint the risk genes) and SP8 as risk loci for BD, SCZ and psychosis. Further replication studies will be required for conclusive results.

Original languageEnglish
Article numbere70964
JournalPLoS One
Volume8
Issue number8
DOIs
Publication statusPublished - 13-08-2013

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Genetic Association Studies
Polymorphism
Bipolar Disorder
Psychotic Disorders
single nucleotide polymorphism
Transcription Factors
Nucleotides
transcription factors
Genes
loci
Single Nucleotide Polymorphism
Schizophrenia
genes
Genome-Wide Association Study
Screening
screening
linkage disequilibrium
schizophrenia
meta-analysis
sampling

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kondo, Kenji ; Ikeda, Masashi ; Kajio, Yusuke ; Saito, Takeo ; Iwayama, Yoshimi ; Aleksic, Branko ; Yamada, Kazuo ; Toyota, Tomoko ; Hattori, Eiji ; Ujike, Hiroshi ; Inada, Toshiya ; Kunugi, Hiroshi ; Kato, Tadafumi ; Yoshikawa, Takeo ; Ozaki, Norio ; Iwata, Nakao. / Genetic Variants on 3q21 and in the Sp8 Transcription Factor Gene (SP8) as Susceptibility Loci for Psychotic Disorders : A Genetic Association Study. In: PLoS One. 2013 ; Vol. 8, No. 8.
@article{225667c5ddba46939561f087f4fa5bb8,
title = "Genetic Variants on 3q21 and in the Sp8 Transcription Factor Gene (SP8) as Susceptibility Loci for Psychotic Disorders: A Genetic Association Study",
abstract = "Background:Recent genome-wide association studies (GWASs) investigating bipolar disorder (BD) have detected a number of susceptibility genes. These studies have also provided novel insight into shared genetic components between BD and schizophrenia (SCZ), two major psychotic disorders. To examine the replication of the risk variants for BD and the pleiotropic effect of the variants associated with BD, we conducted a genetic association study of single nucleotide polymorphisms (SNPs) that were selected based upon previous BD GWASs, which targeted psychotic disorders (BD and SCZ) in the Japanese population.Methods:Forty-eight SNPs were selected based upon previous GWASs. A two-stage analysis was conducted using first-set screening (for all SNPs: BD = 1,012, SCZ = 1,032 and control = 993) and second-set replication samples (for significant SNPs in the screening analysis: BD = 821, SCZ = 1,808 and control = 2,149). We assessed allelic association between BD, SCZ, psychosis (BD+SCZ) and the SNPs selected for the analysis.Results:Eight SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05). Among these SNPs, the top two SNPs (associated with psychosis: Pcorrected = 0.048 and 0.037 for rs2251219 and rs2709722, respectively) were further assessed in the second-set samples, and we replicated the signals from the initial screening analysis (associated with psychosis: Pcorrected = 0.0070 and 0.033 for rs2251219 and rs2709722, respectively). The meta-analysis between the current and previous GWAS results showed that rs2251219 in Polybromo1 (PBRM1) was significant on genome-wide association level (P = 5×10-8) only for BD (P = 9.4×10-9) and psychosis (P = 2.0×10-10). Although the association of rs2709722 in Sp8 transcription factor (SP8) was suggestive in the Asian population (P = 2.1×10-7 for psychosis), this signal weakened when the samples size was increased by including data from a Caucasian population (P = 4.3×10-3).Conclusions:We found 3p21.1 (including PBRM1, strong linkage disequilibrium made it difficult to pinpoint the risk genes) and SP8 as risk loci for BD, SCZ and psychosis. Further replication studies will be required for conclusive results.",
author = "Kenji Kondo and Masashi Ikeda and Yusuke Kajio and Takeo Saito and Yoshimi Iwayama and Branko Aleksic and Kazuo Yamada and Tomoko Toyota and Eiji Hattori and Hiroshi Ujike and Toshiya Inada and Hiroshi Kunugi and Tadafumi Kato and Takeo Yoshikawa and Norio Ozaki and Nakao Iwata",
year = "2013",
month = "8",
day = "13",
doi = "10.1371/journal.pone.0070964",
language = "English",
volume = "8",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",

}

Kondo, K, Ikeda, M, Kajio, Y, Saito, T, Iwayama, Y, Aleksic, B, Yamada, K, Toyota, T, Hattori, E, Ujike, H, Inada, T, Kunugi, H, Kato, T, Yoshikawa, T, Ozaki, N & Iwata, N 2013, 'Genetic Variants on 3q21 and in the Sp8 Transcription Factor Gene (SP8) as Susceptibility Loci for Psychotic Disorders: A Genetic Association Study', PLoS One, vol. 8, no. 8, e70964. https://doi.org/10.1371/journal.pone.0070964

Genetic Variants on 3q21 and in the Sp8 Transcription Factor Gene (SP8) as Susceptibility Loci for Psychotic Disorders : A Genetic Association Study. / Kondo, Kenji; Ikeda, Masashi; Kajio, Yusuke; Saito, Takeo; Iwayama, Yoshimi; Aleksic, Branko; Yamada, Kazuo; Toyota, Tomoko; Hattori, Eiji; Ujike, Hiroshi; Inada, Toshiya; Kunugi, Hiroshi; Kato, Tadafumi; Yoshikawa, Takeo; Ozaki, Norio; Iwata, Nakao.

In: PLoS One, Vol. 8, No. 8, e70964, 13.08.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic Variants on 3q21 and in the Sp8 Transcription Factor Gene (SP8) as Susceptibility Loci for Psychotic Disorders

T2 - A Genetic Association Study

AU - Kondo, Kenji

AU - Ikeda, Masashi

AU - Kajio, Yusuke

AU - Saito, Takeo

AU - Iwayama, Yoshimi

AU - Aleksic, Branko

AU - Yamada, Kazuo

AU - Toyota, Tomoko

AU - Hattori, Eiji

AU - Ujike, Hiroshi

AU - Inada, Toshiya

AU - Kunugi, Hiroshi

AU - Kato, Tadafumi

AU - Yoshikawa, Takeo

AU - Ozaki, Norio

AU - Iwata, Nakao

PY - 2013/8/13

Y1 - 2013/8/13

N2 - Background:Recent genome-wide association studies (GWASs) investigating bipolar disorder (BD) have detected a number of susceptibility genes. These studies have also provided novel insight into shared genetic components between BD and schizophrenia (SCZ), two major psychotic disorders. To examine the replication of the risk variants for BD and the pleiotropic effect of the variants associated with BD, we conducted a genetic association study of single nucleotide polymorphisms (SNPs) that were selected based upon previous BD GWASs, which targeted psychotic disorders (BD and SCZ) in the Japanese population.Methods:Forty-eight SNPs were selected based upon previous GWASs. A two-stage analysis was conducted using first-set screening (for all SNPs: BD = 1,012, SCZ = 1,032 and control = 993) and second-set replication samples (for significant SNPs in the screening analysis: BD = 821, SCZ = 1,808 and control = 2,149). We assessed allelic association between BD, SCZ, psychosis (BD+SCZ) and the SNPs selected for the analysis.Results:Eight SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05). Among these SNPs, the top two SNPs (associated with psychosis: Pcorrected = 0.048 and 0.037 for rs2251219 and rs2709722, respectively) were further assessed in the second-set samples, and we replicated the signals from the initial screening analysis (associated with psychosis: Pcorrected = 0.0070 and 0.033 for rs2251219 and rs2709722, respectively). The meta-analysis between the current and previous GWAS results showed that rs2251219 in Polybromo1 (PBRM1) was significant on genome-wide association level (P = 5×10-8) only for BD (P = 9.4×10-9) and psychosis (P = 2.0×10-10). Although the association of rs2709722 in Sp8 transcription factor (SP8) was suggestive in the Asian population (P = 2.1×10-7 for psychosis), this signal weakened when the samples size was increased by including data from a Caucasian population (P = 4.3×10-3).Conclusions:We found 3p21.1 (including PBRM1, strong linkage disequilibrium made it difficult to pinpoint the risk genes) and SP8 as risk loci for BD, SCZ and psychosis. Further replication studies will be required for conclusive results.

AB - Background:Recent genome-wide association studies (GWASs) investigating bipolar disorder (BD) have detected a number of susceptibility genes. These studies have also provided novel insight into shared genetic components between BD and schizophrenia (SCZ), two major psychotic disorders. To examine the replication of the risk variants for BD and the pleiotropic effect of the variants associated with BD, we conducted a genetic association study of single nucleotide polymorphisms (SNPs) that were selected based upon previous BD GWASs, which targeted psychotic disorders (BD and SCZ) in the Japanese population.Methods:Forty-eight SNPs were selected based upon previous GWASs. A two-stage analysis was conducted using first-set screening (for all SNPs: BD = 1,012, SCZ = 1,032 and control = 993) and second-set replication samples (for significant SNPs in the screening analysis: BD = 821, SCZ = 1,808 and control = 2,149). We assessed allelic association between BD, SCZ, psychosis (BD+SCZ) and the SNPs selected for the analysis.Results:Eight SNPs revealed nominal association signals for all comparisons (Puncorrected<0.05). Among these SNPs, the top two SNPs (associated with psychosis: Pcorrected = 0.048 and 0.037 for rs2251219 and rs2709722, respectively) were further assessed in the second-set samples, and we replicated the signals from the initial screening analysis (associated with psychosis: Pcorrected = 0.0070 and 0.033 for rs2251219 and rs2709722, respectively). The meta-analysis between the current and previous GWAS results showed that rs2251219 in Polybromo1 (PBRM1) was significant on genome-wide association level (P = 5×10-8) only for BD (P = 9.4×10-9) and psychosis (P = 2.0×10-10). Although the association of rs2709722 in Sp8 transcription factor (SP8) was suggestive in the Asian population (P = 2.1×10-7 for psychosis), this signal weakened when the samples size was increased by including data from a Caucasian population (P = 4.3×10-3).Conclusions:We found 3p21.1 (including PBRM1, strong linkage disequilibrium made it difficult to pinpoint the risk genes) and SP8 as risk loci for BD, SCZ and psychosis. Further replication studies will be required for conclusive results.

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