title: Functional relevance for associations between osteoporosis and genetic variants.
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.
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Kun
authors.identifier: http://orcid.org/0000-0001-6206-389X
authors.initials: K
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Tan
authors.affiliation: Physical Examination Department, Guangxi medical university First affiliated hospital, Nanning, Guangxi, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Xiang-Ding
authors.initials: XD
authors.lastname: Chen
authors.affiliation: Physical Examination Department, Guangxi medical university First affiliated hospital, Nanning, Guangxi, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhu
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zeng
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.|Center of Bioinformatics and Genomics, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States of America.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D015519:Bone Density / Q000235:genetics; D030541:Databases, Genetic; D066264:Datasets as Topic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D010024:Osteoporosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci