全基因组关联研究（GWAS）、表达数量性状基因座（eQTL）和甲基化数量性状基因座（meQTL）数据的综合分析表明，多个基因集与骨密度相关。
Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density.
作者信息
Wang W, Huang S, Hou W, Liu Y, Fan Q, He A, Wen Y, Hao J, Guo X, Zhang F
机构信息
School of Public Health, Department of Breast Surgery, First Affiliated Hospital, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Radiotherapy, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
出版信息
Bone Joint Res. 2017 Oct;6(10):572-576. doi: 10.1302/2046-3758.610.BJR-2017-0113.R1.
OBJECTIVES
Several genome-wide association studies (GWAS) of bone mineral density (BMD) have successfully identified multiple susceptibility genes, yet isolated susceptibility genes are often difficult to interpret biologically. The aim of this study was to unravel the genetic background of BMD at pathway level, by integrating BMD GWAS data with genome-wide expression quantitative trait loci (eQTLs) and methylation quantitative trait loci (meQTLs) data METHOD: We employed the GWAS datasets of BMD from the Genetic Factors for Osteoporosis Consortium (GEFOS), analysing patients' BMD. The areas studied included 32 735 femoral necks, 28 498 lumbar spines, and 8143 forearms. Genome-wide eQTLs (containing 923 021 eQTLs) and meQTLs (containing 683 152 unique methylation sites with local meQTLs) data sets were collected from recently published studies. Gene scores were first calculated by summary data-based Mendelian randomisation (SMR) software and meQTL-aligned GWAS results. Gene set enrichment analysis (GSEA) was then applied to identify BMD-associated gene sets with a predefined significance level of 0.05.
RESULTS
We identified multiple gene sets associated with BMD in one or more regions, including relevant known biological gene sets such as the Reactome Circadian Clock (GSEA p-value = 1.0 × 10 for LS and 2.7 × 10 for femoral necks BMD in eQTLs-based GSEA) and insulin-like growth factor receptor binding (GSEA p-value = 5.0 × 10 for femoral necks and 2.6 × 10 for lumbar spines BMD in meQTLs-based GSEA).
CONCLUSION
Our results provided novel clues for subsequent functional analysis of bone metabolism, and illustrated the benefit of integrating eQTLs and meQTLs data into pathway association analysis for genetic studies of complex human diseases.: W. Wang, S. Huang, W. Hou, Y. Liu, Q. Fan, A. He, Y. Wen, J. Hao, X. Guo, F. Zhang. Integrative analysis of GWAS, eQTLs and meQTLs data suggests that multiple gene sets are associated with bone mineral density. 2017;6:572-576.
目的
多项骨密度（BMD）全基因组关联研究（GWAS）已成功鉴定出多个易感基因，但单个易感基因往往难以从生物学角度进行解释。本研究旨在通过整合BMD的GWAS数据与全基因组表达定量性状位点（eQTL）和甲基化定量性状位点（meQTL）数据，在通路水平上揭示BMD的遗传背景。方法：我们采用了来自骨质疏松症遗传因素联盟（GEFOS）的BMD的GWAS数据集，分析患者的骨密度。研究部位包括32735个股骨颈、28498个腰椎和8143个前臂。全基因组eQTL（包含923021个eQTL）和meQTL（包含683152个具有局部meQTL的独特甲基化位点）数据集取自最近发表的研究。首先通过基于汇总数据的孟德尔随机化（SMR）软件和与meQTL对齐的GWAS结果计算基因分数。然后应用基因集富集分析（GSEA）来鉴定与BMD相关的基因集，预定义的显著性水平为0.05。
结果
我们在一个或多个区域中鉴定出多个与BMD相关的基因集，包括相关的已知生物学基因集，如Reactome昼夜节律时钟（基于eQTL的GSEA中，LS的GSEA p值 = 1.0×10，股骨颈BMD的GSEA p值 = 2.7×10）和胰岛素样生长因子受体结合（基于meQTL的GSEA中，股骨颈的GSEA p值 = 5.0×10，腰椎BMD的GSEA p值 = 2.6×10）。
结论
我们的结果为后续骨代谢功能分析提供了新线索，并说明了将eQTL和meQTL数据整合到通路关联分析中对复杂人类疾病遗传研究的益处。作者：W. Wang、S. Huang、W. Hou、Y. Liu、Q. Fan、A. He、Y. Wen、J. Hao、X. Guo、F. Zhang。GWAS、eQTL和meQTL数据的综合分析表明多个基因集与骨密度相关。2017年；6：572 - 576。
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