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Osteoporosis International
Published in: Osteoporosis International 3/2016

01-03-2016 | Original Article

Integrative analysis of genome-wide association studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck disease patients

Authors: Y. Wen, X. Guo, J. Hao, X. Xiao, W. Wang, C. Wu, S. Wang, T. Yang, H. Shen, X. Chen, L. Tan, Q. Tian, H.-W. Deng, F. Zhang

Published in: Osteoporosis International | Issue 3/2016

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Abstract

Summary

The molecular mechanism of osteoporosis (OP) in Kashin-Beck disease (KBD) patients was unclear. Our results suggest that KBD and OP shared some common causal genes, functionally involved in skeletal growth and development and chronic inflammation. Our results provide novel clues for clarifying the molecular mechanism of OP in KBD patients.

Introduction

KBD is a chronic skeletal disorder with osteopenia and OP. The pathogenesis of OP in KBD patients remains elusive.

Methods

A total of 1717 subjects participated in this study. KBD was diagnosed according to the clinical diagnosis criteria of China (GB16395-1996). The bone mineral density (BMD) and bone areas of the ulna and radius, hip, and lumbar (L1–L4) were measured with a Hologic 4500 W dual-energy X-ray absorptiometry scanner. Genotyping was conducted using Affymetrix SNP Array 6.0. Gene expression profiling of peripheral blood mononuclear cells of KBD and OP patients were compared using Affymetrix HG-U133 plus 2.0 arrays and Agilent Human 1A arrays, respectively. Genome-wide association studies (GWAS) were conducted by PLINK. SCEA and DAVID were applied for pleiotropy and functional enrichment analysis, respectively.

Results

SCEA analysis observed significant pleiotropic effects between KBD and the ulna and radius BMD (P value = 5.99 × 10−3). GWAS meta-analysis identified six candidate genes with pleiotropic effects, including PDGFD, SOX5, DPYD, CTR9, SPP1, and COL4A1. GO analysis identified 16 significant GO shared by KBD and the ulna and radius BMD, involved in cell morphogenesis and apoptosis. Pathway enrichment analysis detected two common pathways for KBD and the ulna and radius BMD, including calcium signaling pathway and vascular smooth muscle contraction pathway. Gene expression analysis detected three up-regulated inflammation-related genes for KBD and OP, including IL1B, IL8, and CCL1.

Conclusion

This study reported several candidate genes involved in the development of OP in KBD patients.
Appendix
Available only for authorised users
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Metadata
Title
Integrative analysis of genome-wide association studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck disease patients
Authors
Y. Wen
X. Guo
J. Hao
X. Xiao
W. Wang
C. Wu
S. Wang
T. Yang
H. Shen
X. Chen
L. Tan
Q. Tian
H.-W. Deng
F. Zhang
Publication date
01-03-2016
Publisher
Springer London
Published in
Osteoporosis International / Issue 3/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-015-3364-y

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