Ham Seokjin, Roh Tae-Young
Department of Life Sciences, POSTECH, Pohang 790-784, Korea.
Department of Life Sciences, POSTECH, Pohang 790-784, Korea. ; Division of Integrative Biosciences and Biotechnology, POSTECH, Pohang 790-784, Korea.
Genomics Inform. 2014 Sep;12(3):114-20. doi: 10.5808/GI.2014.12.3.114. Epub 2014 Sep 30.
Bone mineral density (BMD) is one of the quantitative traits that are genetically inherited and affected by various factors. Over the past years, genome-wide association studies (GWASs) have searched for many genetic loci that influence BMD. A recent meta-analysis of 17 GWASs for BMD of the femoral neck and lumbar spine is the largest GWAS for BMD to date and offers 64 single-nucleotide polymorphisms (SNPs) in 56 associated loci. We investigated these BMD loci in a Korean population called Korea Association REsource (KARE) to identify their validity in an independent study. The KARE population contains genotypes from 8,842 individuals, and their BMD levels were measured at the distal radius (BMD-RT) and midshaft tibia (BMD-TT). Thirteen genomic loci among 56 loci were significantly associated with BMD variations, and 3 loci were involved in known biological pathways related to BMD. In order to find putative functional variants, nearby SNPs in relation to linkage equilibrium were annotated, and their possible functional effects were predicted. These findings reveal that tens of variants, not a single factor, may contribute to the genetic architecture of BMD; have an important role regardless of ethnic group; and may highlight the importance of a replication study in GWASs to validate genuine loci for BMD variation.
骨密度（BMD）是一种受遗传因素影响且受多种因素作用的数量性状。在过去几年中，全基因组关联研究（GWAS）已寻找出许多影响骨密度的基因位点。最近一项针对股骨颈和腰椎骨密度的17项GWAS的荟萃分析是迄今为止规模最大的骨密度GWAS研究，该研究在56个相关位点中发现了64个单核苷酸多态性（SNP）。我们在一个名为韩国关联资源（KARE）的韩国人群中对这些骨密度位点进行了研究，以在独立研究中确定它们的有效性。KARE人群包含8842名个体的基因型，并且在桡骨远端（BMD-RT）和胫骨骨干中部（BMD-TT）测量了他们的骨密度水平。56个位点中的13个基因组位点与骨密度变异显著相关，并且3个位点参与了与骨密度相关的已知生物学途径。为了找到推定的功能变异，对处于连锁平衡状态的附近SNP进行了注释，并预测了它们可能的功能效应。这些发现表明，可能是数十个变异而非单一因素对骨密度的遗传结构产生影响；无论种族如何都具有重要作用；并且可能凸显了GWAS中重复研究对于验证骨密度变异真实位点的重要性。
