Genome-wide association study of lncRNA polymorphisms with bone mineral density.
Genome-wide association study of lncRNA polymorphisms with bone mineral density.
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lncRNA 多态性与骨矿物质密度的全基因组关联研究。
DOI：
10.1111/ahg.12247
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发表时间：
2018-09
影响因子：
1.9
通讯作者：
Tan LJ
中科院分区：
文献类型：
--
作者：
Zeng Q;Wu KH;Liu K;Hu Y;Chen XD;Zhang L;Shen H;Tian Q;Zhao LJ;Deng HW;Tan LJ
最近的研究表明，长非编码RNA(LncRNAs)在基因组中广泛转录，但它们在人类疾病遗传复杂性中的潜在作用有待进一步研究。本研究旨在探讨与骨密度(BMD)相关的LncRNAs基因多态性及其潜在价值。基于LncRNASNP数据库，选取55,906个LncSNP对11,140名个体进行了全基因组关联研究荟萃分析，这些个体来自7项关于股骨颈(FN)、腰椎和全髋部骨密度(BMD)的独立研究。在骨质疏松症协会的遗传因素(GEFOS测序，n=32,965)中复制了有希望的结果。我们发现了两个与BMD显著相关的lncRNA基因座。经Bonferroni校正后，位于5q14.3的MEF2C反义RNA1(MEF2C-AS1)与Fn-BMD显著相关，其中rs6894139的结合信号最强(P=3.03×10−9)。位于7q21.3的Loc100506136rs6465531与髋部骨密度显著相关(P=7.43×10−7)。MEF2C-AS1rs6894139在GEFOS测序中重复，P值为1.43×10−23。我们的结果说明了LncRNAs基因的多态性在决定BMD变异中的重要作用，并为后续的功能研究提供了证据和依据。
Recent studies suggested that long noncoding RNAs (lncRNAs) were widely transcribed in the genome, but their potential roles in the genetic complexity of human disorders required further exploration. The purpose of the present study was to explore genetic polymorphisms of lncRNAs associated with bone mineral density (BMD) and its potential value. Based on the lncRNASNP database, 55,906 lncSNPs were selected to conduct a genome-wide association study meta-analysis among 11,140 individuals of seven independent studies for BMDs at femoral neck (FN), lumbar spine, and total hip (HIP). Promising results were replicated in Genetic Factors for Osteoporosis Consortium (GEFOS Sequencing, n = 32,965). We found two lncRNA loci that were significantly associated with BMD. MEF2C antisense RNA 1 (MEF2C-AS1) located at 5q14.3 was significantly associated with FN-BMD after Bonferroni correction, and the strongest association signal was detected at rs6894139 (P = 3.03 × 10−9). LOC100506136 rs6465531 located at 7q21.3 showed significant association with HIP-BMD (P = 7.43 × 10−7). MEF2C-AS1 rs6894139 was replicated in GEFOS Sequencing with P-value of 1.43 × 10−23. Our results illustrated the important role of polymorphisms in lncRNAs in determining variations of BMD and provided justification and evidence for subsequent functional studies.
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