A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder

Advanced Collaborative Study of Mood Disorder (COSMO) team

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10 '9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best =5.8 × 10 '10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best =1.9 × 10 '9), TRANK1 (P best =2.1 × 10 '9) and ODZ4 (P best =3.3 × 10 '9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', P best ∼10 '29, R 2 ∼2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' P best ∼10 '13, R 2 ∼0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates∼0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

Original languageEnglish
Pages (from-to)639-647
Number of pages9
JournalMolecular Psychiatry
Volume23
Issue number3
DOIs
Publication statusPublished - 01-03-2018

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Genome-Wide Association Study
Bipolar Disorder
Population
Psychiatry
Regulator Genes
Meta-Analysis

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

@article{9e79b88616d34c3f8db8eda1e3eb2ece,
title = "A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder",
abstract = "Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10 '9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best =5.8 × 10 '10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best =1.9 × 10 '9), TRANK1 (P best =2.1 × 10 '9) and ODZ4 (P best =3.3 × 10 '9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', P best ∼10 '29, R 2 ∼2{\%}), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' P best ∼10 '13, R 2 ∼0.27{\%}). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates∼0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.",
author = "{Advanced Collaborative Study of Mood Disorder (COSMO) team} and M. Ikeda and Masashi Ikeda and Y. Kamatani and Y. Okahisa and H. Kunugi and N. Mori and T. Sasaki and T. Ohmori and Y. Okamoto and H. Kawasaki and S. Shimodera and T. Kato and H. Yoneda and R. Yoshimura and M. Iyo and K. Matsuda and M. Akiyama and K. Ashikawa and K. Kashiwase and K. Tokunaga and K. Kondo and T. Saito and Takeo Saito and K. Kawase and T. Kitajima and Tsuyoshi Kitajima and M. Itokawa and T. Someya and T. Inada and R. Hashimoto and T. Inoue and K. Akiyama and H. Tanii and H. Arai and S. Kanba and N. Ozaki and I. Kusumi and T. Yoshikawa and M. Kubo and Nakao Iwata",
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A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder. / Advanced Collaborative Study of Mood Disorder (COSMO) team.

In: Molecular Psychiatry, Vol. 23, No. 3, 01.03.2018, p. 639-647.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder

AU - Advanced Collaborative Study of Mood Disorder (COSMO) team

AU - Ikeda, M.

AU - Ikeda, Masashi

AU - Kamatani, Y.

AU - Okahisa, Y.

AU - Kunugi, H.

AU - Mori, N.

AU - Sasaki, T.

AU - Ohmori, T.

AU - Okamoto, Y.

AU - Kawasaki, H.

AU - Shimodera, S.

AU - Kato, T.

AU - Yoneda, H.

AU - Yoshimura, R.

AU - Iyo, M.

AU - Matsuda, K.

AU - Akiyama, M.

AU - Ashikawa, K.

AU - Kashiwase, K.

AU - Tokunaga, K.

AU - Kondo, K.

AU - Saito, T.

AU - Saito, Takeo

AU - Kawase, K.

AU - Kitajima, T.

AU - Kitajima, Tsuyoshi

AU - Itokawa, M.

AU - Someya, T.

AU - Inada, T.

AU - Hashimoto, R.

AU - Inoue, T.

AU - Akiyama, K.

AU - Tanii, H.

AU - Arai, H.

AU - Kanba, S.

AU - Ozaki, N.

AU - Kusumi, I.

AU - Yoshikawa, T.

AU - Kubo, M.

AU - Iwata, Nakao

PY - 2018/3/1

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N2 - Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10 '9), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best =5.8 × 10 '10), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best =1.9 × 10 '9), TRANK1 (P best =2.1 × 10 '9) and ODZ4 (P best =3.3 × 10 '9). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', P best ∼10 '29, R 2 ∼2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' P best ∼10 '13, R 2 ∼0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates∼0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

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