A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density

Ruqi Tang, Yiran Wei, Zhiqiang Li, Haoyan Chen, Qi Miao, Zhaolian Bian, Haiyan Zhang, Qixia Wang, Zhaoyue Wang, Min Lian, Fan Yang, Xiang Jiang, Yue Yang, Enling Li, Michael F Seldin, M. Eric Gershwin, Wilson Liao, Yongyong Shi, Xiong Ma

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13 Scopus citations


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, Pfdr = 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 (Pcombined = 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 (Padj = 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.

Original languageEnglish (US)
Article number19877
JournalScientific Reports
StatePublished - Feb 4 2016

ASJC Scopus subject areas

  • General


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