Gene-based association analysis identified novel genes associated with bone mineral density

Xing-Bo Mo; Xin Lu; Yong-Hong Zhang; Zeng-Li Zhang; Fei-Yan Deng; Shu-Feng Lei

doi:10.1371/journal.pone.0121811

Gene-based association analysis identified novel genes associated with bone mineral density

PLoS One. 2015 Mar 26;10(3):e0121811. doi: 10.1371/journal.pone.0121811. eCollection 2015.

Authors

Xing-Bo Mo¹, Xin Lu², Yong-Hong Zhang¹, Zeng-Li Zhang², Fei-Yan Deng², Shu-Feng Lei¹

Affiliations

¹ Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, P. R. China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, P. R. China; Department of Epidemiology, School of Public Health, Soochow University, Suzhou, Jiangsu, P. R. China.
² Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu, P. R. China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, Jiangsu, P. R. China.

Abstract

Genetic factors contribute to the variation of bone mineral density (BMD), which is a major risk factor of osteoporosis. The aim of this study was to identify more "novel" genes for BMD. Based on the publicly available SNP-based P values, we performed an initial gene-based analysis in a total of 32,961 individuals. Furthermore, we performed differential expression, pathway and protein-protein interaction analyses to find supplementary evidence to support the significance of the identified genes. About 21,695 genes for femoral neck (FN)-BMD and 21,683 genes for lumbar spine (LS)-BMD were analyzed using gene-based association analysis. A total of 35 FN-BMD associated genes and 53 LS-BMD associated genes were identified (P < 2.3×10(-6)) after Bonferroni correction. Among them, 64 genes have not been reported in previous SNP-based genome-wide association studies. Differential expression analysis further supported the significant associations of 14 genes with FN-BMD and 19 genes with LS-BMD. Especially, WNT3 and WNT9B in the Wnt signaling pathway for FN-BMD were further supported by pathway analysis and protein-protein interaction analysis. The present study took the advantage of gene-based association method to perform a supplementary analysis of the GWAS dataset and found some BMD-associated genes. The evidence taken together supported the importance of Wnt signaling pathway genes in determining osteoporosis. Our findings provided more insights into the genetic basis of osteoporosis.

Publication types

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

MeSH terms

Bone Density / genetics*
Computational Biology / methods
Databases, Nucleic Acid
Gene Expression Profiling
Gene Expression Regulation
Genetic Association Studies*
Genetic Predisposition to Disease
Genome-Wide Association Study*
Genomics / methods
Humans
Polymorphism, Single Nucleotide
Protein Interaction Mapping
Protein Interaction Maps
Signal Transduction

Grants and funding

The study was supported by Natural Science Foundation of China (31401079, 81373010, 81473046, 81401343, 31271336, and 31071097), the natural science foundation of Jiangsu Province (BK20130300), the Startup Fund from Soochow University (Q413900313, Q413900112, Q413900712), Project funded by China Postdoctoral Science Foundation (2014M551649), and a Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.