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A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density
Primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, has been associated with increased incidence of osteoporosis. Intriguingly, two PBC susceptibility loci identified through genome-wide association studies are also involved in bone mineral density (BMD). These observations led us t...
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/PMC4740766/ https://www.ncbi.nlm.nih.gov/pubmed/26842849 http://dx.doi.org/10.1038/srep19877 |
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author | Tang, Ruqi Wei, Yiran Li, Zhiqiang Chen, Haoyan Miao, Qi Bian, Zhaolian Zhang, Haiyan Wang, Qixia Wang, Zhaoyue Lian, Min Yang, Fan Jiang, Xiang Yang, Yue Li, Enling Seldin, Michael F. Gershwin, M. Eric Liao, Wilson Shi, Yongyong Ma, Xiong |
author_facet | Tang, Ruqi Wei, Yiran Li, Zhiqiang Chen, Haoyan Miao, Qi Bian, Zhaolian Zhang, Haiyan Wang, Qixia Wang, Zhaoyue Lian, Min Yang, Fan Jiang, Xiang Yang, Yue Li, Enling Seldin, Michael F. Gershwin, M. Eric Liao, Wilson Shi, Yongyong Ma, Xiong |
author_sort | Tang, Ruqi |
collection | PubMed |
description | Primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, has been associated with increased incidence of osteoporosis. Intriguingly, two PBC susceptibility loci identified through genome-wide association studies are also involved in bone mineral density (BMD). These observations led us to investigate the genetic variants shared between PBC and BMD. We evaluated 72 genome-wide significant BMD SNPs for association with PBC using two European GWAS data sets (n = 8392), with replication of significant findings in a Chinese cohort (685 cases, 1152 controls). Our analysis identified a novel variant in the intron of the CLDN14 gene (rs170183, P(fdr) = 0.015) after multiple testing correction. The three associated variants were followed-up in the Chinese cohort; one SNP rs170183 demonstrated consistent evidence of association in diverse ethnic populations (P(combined) = 2.43 × 10(−5)). Notably, expression quantitative trait loci (eQTL) data revealed that rs170183 was correlated with a decline in CLDN14 expression in both lymphoblastoid cell lines and T cells (P(adj) = 0.003 and 0.016, respectively). In conclusion, our study identified a novel PBC susceptibility variant that has been shown to be strongly associated with BMD, highlighting the potential of pleiotropy to improve gene discovery. |
format | Online Article Text |
id | pubmed-4740766 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47407662016-02-09 A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density Tang, Ruqi Wei, Yiran Li, Zhiqiang Chen, Haoyan Miao, Qi Bian, Zhaolian Zhang, Haiyan Wang, Qixia Wang, Zhaoyue Lian, Min Yang, Fan Jiang, Xiang Yang, Yue Li, Enling Seldin, Michael F. Gershwin, M. Eric Liao, Wilson Shi, Yongyong Ma, Xiong Sci Rep Article Primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, has been associated with increased incidence of osteoporosis. Intriguingly, two PBC susceptibility loci identified through genome-wide association studies are also involved in bone mineral density (BMD). These observations led us to investigate the genetic variants shared between PBC and BMD. We evaluated 72 genome-wide significant BMD SNPs for association with PBC using two European GWAS data sets (n = 8392), with replication of significant findings in a Chinese cohort (685 cases, 1152 controls). Our analysis identified a novel variant in the intron of the CLDN14 gene (rs170183, P(fdr) = 0.015) after multiple testing correction. The three associated variants were followed-up in the Chinese cohort; one SNP rs170183 demonstrated consistent evidence of association in diverse ethnic populations (P(combined) = 2.43 × 10(−5)). Notably, expression quantitative trait loci (eQTL) data revealed that rs170183 was correlated with a decline in CLDN14 expression in both lymphoblastoid cell lines and T cells (P(adj) = 0.003 and 0.016, respectively). In conclusion, our study identified a novel PBC susceptibility variant that has been shown to be strongly associated with BMD, highlighting the potential of pleiotropy to improve gene discovery. Nature Publishing Group 2016-02-04 /pmc/articles/PMC4740766/ /pubmed/26842849 http://dx.doi.org/10.1038/srep19877 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 Tang, Ruqi Wei, Yiran Li, Zhiqiang Chen, Haoyan Miao, Qi Bian, Zhaolian Zhang, Haiyan Wang, Qixia Wang, Zhaoyue Lian, Min Yang, Fan Jiang, Xiang Yang, Yue Li, Enling Seldin, Michael F. Gershwin, M. Eric Liao, Wilson Shi, Yongyong Ma, Xiong A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density |
title | A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density |
title_full | A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density |
title_fullStr | A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density |
title_full_unstemmed | A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density |
title_short | A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density |
title_sort | common variant in cldn14 is associated with primary biliary cirrhosis and bone mineral density |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740766/ https://www.ncbi.nlm.nih.gov/pubmed/26842849 http://dx.doi.org/10.1038/srep19877 |
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