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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
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.
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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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