title: Integrative analysis of genome-wide association studies and gene expression profiles identified candidate genes for osteoporosis in Kashin-Beck disease patients.
abstract: CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
  
  
  CONCLUSIONS
  This study reported several candidate genes involved in the development of OP in KBD patients.
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wen
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.
authors.forename: J
authors.initials: J
authors.lastname: Hao
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.affiliation: School of Public Health, Health Science Center, Xi'an Jiaotong University, Yan Ta West Road 76, Xi'an, 710061, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: T
authors.initials: T
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, China.
authors.forename: L
authors.initials: L
authors.lastname: Tan
authors.affiliation: 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.
authors.forename: Q
authors.initials: Q
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: H-W
authors.initials: HW
authors.lastname: Deng
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Zhang
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000328:Adult; D015519:Bone Density / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D058685:Genetic Pleiotropy / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D057767:Kashin-Beck Disease / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D011884:Radius / Q000000981:diagnostic imaging / Q000503:physiopathology; D014457:Ulna / Q000000981:diagnostic imaging / Q000503:physiopathology; D055815:Young Adult
keywords: Gene expression profile; Genome-wide association study; Kashin-Beck disease; Osteoporosis; Pleiotropy