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

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...

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Autores principales: Ikeda, M, Takahashi, A, Kamatani, Y, Okahisa, Y, Kunugi, H, Mori, N, Sasaki, T, Ohmori, T, Okamoto, Y, Kawasaki, H, Shimodera, S, Kato, T, Yoneda, H, Yoshimura, R, Iyo, M, Matsuda, K, Akiyama, M, Ashikawa, K, Kashiwase, K, Tokunaga, K, Kondo, K, Saito, T, Shimasaki, A, Kawase, K, Kitajima, T, Matsuo, K, Itokawa, M, Someya, T, Inada, T, Hashimoto, R, Inoue, T, Akiyama, K, Tanii, H, Arai, H, Kanba, S, Ozaki, N, Kusumi, I, Yoshikawa, T, Kubo, M, Iwata, N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822448/
https://www.ncbi.nlm.nih.gov/pubmed/28115744
http://dx.doi.org/10.1038/mp.2016.259
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author Ikeda, M
Takahashi, A
Kamatani, Y
Okahisa, Y
Kunugi, H
Mori, N
Sasaki, T
Ohmori, T
Okamoto, Y
Kawasaki, H
Shimodera, S
Kato, T
Yoneda, H
Yoshimura, R
Iyo, M
Matsuda, K
Akiyama, M
Ashikawa, K
Kashiwase, K
Tokunaga, K
Kondo, K
Saito, T
Shimasaki, A
Kawase, K
Kitajima, T
Matsuo, K
Itokawa, M
Someya, T
Inada, T
Hashimoto, R
Inoue, T
Akiyama, K
Tanii, H
Arai, H
Kanba, S
Ozaki, N
Kusumi, I
Yoshikawa, T
Kubo, M
Iwata, N
author_facet Ikeda, M
Takahashi, A
Kamatani, Y
Okahisa, Y
Kunugi, H
Mori, N
Sasaki, T
Ohmori, T
Okamoto, Y
Kawasaki, H
Shimodera, S
Kato, T
Yoneda, H
Yoshimura, R
Iyo, M
Matsuda, K
Akiyama, M
Ashikawa, K
Kashiwase, K
Tokunaga, K
Kondo, K
Saito, T
Shimasaki, A
Kawase, K
Kitajima, T
Matsuo, K
Itokawa, M
Someya, T
Inada, T
Hashimoto, R
Inoue, T
Akiyama, K
Tanii, H
Arai, H
Kanba, S
Ozaki, N
Kusumi, I
Yoshikawa, T
Kubo, M
Iwata, N
author_sort Ikeda, M
collection PubMed
description 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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spelling pubmed-58224482018-02-23 A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder Ikeda, M Takahashi, A Kamatani, Y Okahisa, Y Kunugi, H Mori, N Sasaki, T Ohmori, T Okamoto, Y Kawasaki, H Shimodera, S Kato, T Yoneda, H Yoshimura, R Iyo, M Matsuda, K Akiyama, M Ashikawa, K Kashiwase, K Tokunaga, K Kondo, K Saito, T Shimasaki, A Kawase, K Kitajima, T Matsuo, K Itokawa, M Someya, T Inada, T Hashimoto, R Inoue, T Akiyama, K Tanii, H Arai, H Kanba, S Ozaki, N Kusumi, I Yoshikawa, T Kubo, M Iwata, N Mol Psychiatry Original Article 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. Nature Publishing Group 2018 2017-01-24 /pmc/articles/PMC5822448/ /pubmed/28115744 http://dx.doi.org/10.1038/mp.2016.259 Text en Copyright © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Original Article
Ikeda, M
Takahashi, A
Kamatani, Y
Okahisa, Y
Kunugi, H
Mori, N
Sasaki, T
Ohmori, T
Okamoto, Y
Kawasaki, H
Shimodera, S
Kato, T
Yoneda, H
Yoshimura, R
Iyo, M
Matsuda, K
Akiyama, M
Ashikawa, K
Kashiwase, K
Tokunaga, K
Kondo, K
Saito, T
Shimasaki, A
Kawase, K
Kitajima, T
Matsuo, K
Itokawa, M
Someya, T
Inada, T
Hashimoto, R
Inoue, T
Akiyama, K
Tanii, H
Arai, H
Kanba, S
Ozaki, N
Kusumi, I
Yoshikawa, T
Kubo, M
Iwata, N
A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder
title A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder
title_full A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder
title_fullStr A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder
title_full_unstemmed A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder
title_short A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder
title_sort genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822448/
https://www.ncbi.nlm.nih.gov/pubmed/28115744
http://dx.doi.org/10.1038/mp.2016.259
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