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Integrative analysis of genome-wide association studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck disease patients.
Osteoporos Int. 2016 Mar; 27(3):1041-1046.OI

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.

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Authors+Show Affiliations

School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.

Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.

Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA. Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, USA.

Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China.

Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China.

Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA. Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, USA.

Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA. Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, USA.

School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China. fzhxjtu@mail.xjtu.edu.cn.

MeSH

Absorptiometry, PhotonAdultBone DensityFemaleGene Expression ProfilingGenetic PleiotropyGenome-Wide Association StudyHumansKashin-Beck DiseaseMaleMiddle AgedOsteoporosisRadiusUlnaYoung Adult

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26462493

Citation

Wen, Y, et al. "Integrative Analysis of Genome-wide Association Studies and Gene Expression Profiles Identified Candidate Genes for Osteoporosis in Kashin-Beck Disease Patients." Osteoporosis International : a Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, vol. 27, no. 3, 2016, pp. 1041-1046.

Wen Y, Guo X, Hao J, et al. Integrative analysis of genome-wide association studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck disease patients. Osteoporos Int. 2016;27(3):1041-1046.

Wen, Y., Guo, X., Hao, J., Xiao, X., Wang, W., Wu, C., Wang, S., Yang, T., Shen, H., Chen, X., Tan, L., Tian, Q., Deng, H. W., & Zhang, F. (2016). Integrative analysis of genome-wide association studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck disease patients. Osteoporosis International : a Journal Established as Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 27(3), 1041-1046. https://doi.org/10.1007/s00198-015-3364-y

Wen Y, et al. Integrative Analysis of Genome-wide Association Studies and Gene Expression Profiles Identified Candidate Genes for Osteoporosis in Kashin-Beck Disease Patients. Osteoporos Int. 2016;27(3):1041-1046. PubMed PMID: 26462493.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Integrative analysis of genome-wide association studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck disease patients. AU - Wen,Y, AU - Guo,X, AU - Hao,J, AU - Xiao,X, AU - Wang,W, AU - Wu,C, AU - Wang,S, AU - Yang,T, AU - Shen,H, AU - Chen,X, AU - Tan,L, AU - Tian,Q, AU - Deng,H-W, AU - Zhang,F, Y1 - 2015/10/13/ PY - 2015/07/23/received PY - 2015/10/01/accepted PY - 2015/10/15/entrez PY - 2015/10/16/pubmed PY - 2016/12/15/medline KW - Gene expression profile KW - Genome-wide association study KW - Kashin-Beck disease KW - Osteoporosis KW - Pleiotropy SP - 1041 EP - 1046 JF - Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA JO - Osteoporos Int VL - 27 IS - 3 N2 - 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. SN - 1433-2965 UR - https://www.unboundmedicine.com/medline/citation/26462493/Integrative_analysis_of_genome_wide_association_studies_and_gene_expression_profiles_identified_candidate_genes_for_osteoporosis_in_Kashin_Beck_disease_patients_ L2 - https://dx.doi.org/10.1007/s00198-015-3364-y DB - PRIME DP - Unbound Medicine ER -