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Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis
Considerable sharing of disease alleles among populations is well-characterized in autoimmune disorders (e.g., rheumatoid arthritis), but there are some exceptional loci showing heterogenic association among populations. Here we investigated genetic variants with distinct effects on the development...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897688/ https://www.ncbi.nlm.nih.gov/pubmed/27272985 http://dx.doi.org/10.1038/srep27563 |
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author | Kim, Kwangwoo Bang, So-Young Ikari, Katsunori Yoo, Dae Hyun Cho, Soo-Kyung Choi, Chan-Bum Sung, Yoon-Kyoung Kim, Tae-Hwan Jun, Jae-Bum Kang, Young Mo Suh, Chang-Hee Shim, Seung-Cheol Lee, Shin-Seok Lee, Jisoo Chung, Won Tae Kim, Seong-Kyu Choe, Jung-Yoon Momohara, Shigeki Taniguchi, Atsuo Yamanaka, Hisashi Nath, Swapan K. Lee, Hye-Soon Bae, Sang-Cheol |
author_facet | Kim, Kwangwoo Bang, So-Young Ikari, Katsunori Yoo, Dae Hyun Cho, Soo-Kyung Choi, Chan-Bum Sung, Yoon-Kyoung Kim, Tae-Hwan Jun, Jae-Bum Kang, Young Mo Suh, Chang-Hee Shim, Seung-Cheol Lee, Shin-Seok Lee, Jisoo Chung, Won Tae Kim, Seong-Kyu Choe, Jung-Yoon Momohara, Shigeki Taniguchi, Atsuo Yamanaka, Hisashi Nath, Swapan K. Lee, Hye-Soon Bae, Sang-Cheol |
author_sort | Kim, Kwangwoo |
collection | PubMed |
description | Considerable sharing of disease alleles among populations is well-characterized in autoimmune disorders (e.g., rheumatoid arthritis), but there are some exceptional loci showing heterogenic association among populations. Here we investigated genetic variants with distinct effects on the development of rheumatoid arthritis in Asian and European populations. Ancestry-related association heterogeneity was examined using Cochran’s homogeneity tests for the disease association data from large Asian (n = 14,465; 9,299 discovery subjects and 5,166 validation subjects; 4 collections) and European (n = 45,790; 11 collections) rheumatoid arthritis case-control cohorts with Immunochip and genome-wide SNP array data. We identified significant heterogeneity between the two ancestries for the common variants in the GTF2I locus (P(Heterogeneity) = 9.6 × 10(−9) at rs73366469) and showed that this heterogeneity was due to an Asian-specific association effect (OR(Meta) = 1.37 and P(Meta) = 4.2 × 10(−13) in Asians; OR(Meta) = 1.00 and P(Meta) = 1.00 in Europeans). Trans-ancestral comparison and bioinfomatics analysis revealed a plausibly causal or disease-variant-tagging SNP (rs117026326; in linkage disequilibrium with rs73366469), whose minor allele is common in Asians but rare in Europeans. In conclusion, we identified largest-ever effect on Asian rheumatoid arthritis across human non-HLA regions at GTF2I by heterogeneity mapping followed by replication studies, and pinpointed a possible causal variant. |
format | Online Article Text |
id | pubmed-4897688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48976882016-06-10 Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis Kim, Kwangwoo Bang, So-Young Ikari, Katsunori Yoo, Dae Hyun Cho, Soo-Kyung Choi, Chan-Bum Sung, Yoon-Kyoung Kim, Tae-Hwan Jun, Jae-Bum Kang, Young Mo Suh, Chang-Hee Shim, Seung-Cheol Lee, Shin-Seok Lee, Jisoo Chung, Won Tae Kim, Seong-Kyu Choe, Jung-Yoon Momohara, Shigeki Taniguchi, Atsuo Yamanaka, Hisashi Nath, Swapan K. Lee, Hye-Soon Bae, Sang-Cheol Sci Rep Article Considerable sharing of disease alleles among populations is well-characterized in autoimmune disorders (e.g., rheumatoid arthritis), but there are some exceptional loci showing heterogenic association among populations. Here we investigated genetic variants with distinct effects on the development of rheumatoid arthritis in Asian and European populations. Ancestry-related association heterogeneity was examined using Cochran’s homogeneity tests for the disease association data from large Asian (n = 14,465; 9,299 discovery subjects and 5,166 validation subjects; 4 collections) and European (n = 45,790; 11 collections) rheumatoid arthritis case-control cohorts with Immunochip and genome-wide SNP array data. We identified significant heterogeneity between the two ancestries for the common variants in the GTF2I locus (P(Heterogeneity) = 9.6 × 10(−9) at rs73366469) and showed that this heterogeneity was due to an Asian-specific association effect (OR(Meta) = 1.37 and P(Meta) = 4.2 × 10(−13) in Asians; OR(Meta) = 1.00 and P(Meta) = 1.00 in Europeans). Trans-ancestral comparison and bioinfomatics analysis revealed a plausibly causal or disease-variant-tagging SNP (rs117026326; in linkage disequilibrium with rs73366469), whose minor allele is common in Asians but rare in Europeans. In conclusion, we identified largest-ever effect on Asian rheumatoid arthritis across human non-HLA regions at GTF2I by heterogeneity mapping followed by replication studies, and pinpointed a possible causal variant. Nature Publishing Group 2016-06-08 /pmc/articles/PMC4897688/ /pubmed/27272985 http://dx.doi.org/10.1038/srep27563 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 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/4.0/ |
spellingShingle | Article Kim, Kwangwoo Bang, So-Young Ikari, Katsunori Yoo, Dae Hyun Cho, Soo-Kyung Choi, Chan-Bum Sung, Yoon-Kyoung Kim, Tae-Hwan Jun, Jae-Bum Kang, Young Mo Suh, Chang-Hee Shim, Seung-Cheol Lee, Shin-Seok Lee, Jisoo Chung, Won Tae Kim, Seong-Kyu Choe, Jung-Yoon Momohara, Shigeki Taniguchi, Atsuo Yamanaka, Hisashi Nath, Swapan K. Lee, Hye-Soon Bae, Sang-Cheol Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis |
title | Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis |
title_full | Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis |
title_fullStr | Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis |
title_full_unstemmed | Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis |
title_short | Association-heterogeneity mapping identifies an Asian-specific association of the GTF2I locus with rheumatoid arthritis |
title_sort | association-heterogeneity mapping identifies an asian-specific association of the gtf2i locus with rheumatoid arthritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4897688/ https://www.ncbi.nlm.nih.gov/pubmed/27272985 http://dx.doi.org/10.1038/srep27563 |
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