Functional relevance for associations between osteoporosis and genetic variants

Kun Liu; Li-Jun Tan; Peng Wang; Xiang-Ding Chen; Li-Hua Zhu; Qin Zeng; Yuan Hu; Hong-Wen Deng

doi:10.1371/journal.pone.0174808

Functional relevance for associations between osteoporosis and genetic variants

PLoS One. 2017 Apr 3;12(4):e0174808. doi: 10.1371/journal.pone.0174808. eCollection 2017.

Authors

Kun Liu¹, Li-Jun Tan¹, Peng Wang², Xiang-Ding Chen¹, Li-Hua Zhu², Qin Zeng¹, Yuan Hu¹, Hong-Wen Deng^{1

3}

Affiliations

¹ Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
² Physical Examination Department, Guangxi medical university First affiliated hospital, Nanning, Guangxi, China.
³ Center of Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States of America.

Abstract

Osteoporosis is characterized by increased bone loss and deterioration of bone microarchitecture, which will lead to reduced bone strength and increased risk of fragility fractures. Previous studies have identified many genetic loci associated with osteoporosis, but functional mechanisms underlying the associations have rarely been explored. In order to explore the potential molecular functional mechanisms underlying the associations for osteoporosis, we performed integrative analyses by using the publically available datasets and resources. We searched 128 identified osteoporosis associated SNPs (P<10-6), and 8 SNPs exert cis-regulation effects on 11 eQTL target genes. Among the 8 SNPs, 2 SNPs (RPL31 rs2278729 and LRP5 rs3736228) were confirmed to impact the expression of 3 genes (RPL31, CPT1A and MTL5) that were differentially expressed between human subjects of high BMD group and low BMD group. All of the functional evidence suggested the important functional mechanisms underlying the associations of the 2 SNPs (rs2278729 and rs3736228) and 3 genes (RPL31, CPT1A and MTL5) with osteoporosis. This study may provide novel insights into the functional mechanisms underlying the osteoporosis associated genetic variants, which will help us to comprehend the potential mechanisms underlying the genetic association for osteoporosis.

MeSH terms

Bone Density / genetics
Databases, Genetic
Datasets as Topic
Female
Gene Expression Profiling
Humans
Osteoporosis / genetics*
Polymorphism, Single Nucleotide*
Quantitative Trait Loci

Grants and funding

This study was supported in part by Natural Science Foundation of China (NSFC; 81570807 to LJT, 31271344 and 31071097) and the Cooperative Innovation Center of Engineering and New Products for Developmental Biology of Hunan Province (20134486). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.