title: A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density.
abstract: 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.
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Ruqi
authors: R
authors: Tang
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Yiran
authors: Y
authors: Wei
authors: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China.
authors: Zhiqiang
authors: Z
authors: Li
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Haoyan
authors: H
authors: Chen
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Qi
authors: Q
authors: Miao
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Zhaolian
authors: Z
authors: Bian
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Haiyan
authors: H
authors: Zhang
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Qixia
authors: Q
authors: Wang
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Zhaoyue
authors: Z
authors: Wang
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Min
authors: M
authors: Lian
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Fan
authors: F
authors: Yang
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Xiang
authors: X
authors: Jiang
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Yue
authors: Y
authors: Yang
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Enling
authors: E
authors: Li
authors: Department of Biochemistry and Molecular Medicine, University of California at Davis, Davis, CA 95616, USA.|Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, USA.
authors: Michael F
authors: MF
authors: Seldin
authors: Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Suite 6510, Davis, CA 95616, USA.
authors: M Eric
authors: ME
authors: Gershwin
authors: Department of Dermatology, University of California San Francisco School of Medicine, 1701 Dividadero Street, San Francisco, CA 94415, USA.
authors: Wilson
authors: W
authors: Liao
authors: Department of Biochemistry and Molecular Medicine, University of California at Davis, Davis, CA 95616, USA.
authors: Yongyong
authors: Y
authors: Shi
authors: State Key Laboratory for Oncogenes and Related Genes, Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Cancer Institute, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China.
authors: Xiong
authors: X
authors: Ma
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D015519:Bone Density / Q000502:physiology*; D045744:Cell Line, Tumor; D057167:Claudins / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D057167:Claudins; C422064:claudin 14