Introduction

Serum urate is associated with BMD and may be a protective factor. However, the exact association and mechanism are still unclear. We performed a genome-wide gene–environmental interaction study (GWGEIS) to explore the interaction effects between gene and urate on BMD, using data from the UK Biobank cohort.

Methods

A total of 4575 participants for femur total BMD, 4561 participants for L1–L4 BMD, and 237799 participants for heel BMD were included in the present study. Linear regression models were used to test for associations between urate and BMD (femur total BMD, L1–L4 BMD, heel BMD) by R software. GWGEIS was conducted by PLINK 2.0 using a generalize linear model, adjusted for age, sex, weight, smoking behavior, drinking behavior, physical activity and 10 principle components for population structure.

Results

Results showed that urate was positively associated with femur total BMD, L1–L4 BMD and heel BMD and similar findings were observed in both the male and female subgroups. GWGEIS identified 261 genome-wide significant (P < 5.00 × 10⁻⁸) SNP × urate interaction effects for femur total BMD (rs8192585 in NOTCH4, rs116080577 in PBX1, rs9409991 in COL5A1), 17 genome-wide significant SNP × urate interaction effects for heel BMD (rs145344540 in PDE11A and rs78485379 in DKK2), 17 suggestive genome-wide SNP × urate interaction effects (P < 1.00 × 10⁻⁵) for L1–L4 BMD (rs10977015 in PTPRD). We also detected genome-wide significant and suggestive SNP × urate interaction effects for BMD in both the male and female subgroups.

Conclusions

This study reported several novel candidate genes, and strengthen the evidence of the interactive effects between gene and urate on the variations of BMD.

中文翻译：

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评估血清尿酸盐水平对骨矿物质密度的影响：英国生物银行队列中的全基因组基因-环境相互作用分析

介绍

血清尿酸盐与 BMD 相关，可能是一个保护因素。然而，确切的关联和机制仍不清楚。我们使用来自英国生物银行队列的数据进行了全基因组基因-环境相互作用研究 (GWGEIS)，以探索基因和尿酸盐对 BMD 的相互作用影响。

方法

本研究共纳入 4575 名股骨总 BMD 参与者、4561 名 L1-L4 BMD 参与者和 237799 名足跟 BMD 参与者。线性回归模型用于通过 R 软件测试尿酸盐和 BMD（股骨总 BMD、L1-L4 BMD、足跟 BMD）之间的关联。GWGEIS 由 PLINK 2.0 使用广义线性模型进行，针对年龄、性别、体重、吸烟行为、饮酒行为、身体活动和人口结构的 10 个主要成分进行了调整。

结果

结果显示，尿酸盐与股骨总骨密度、L1-L4 BMD 和足跟骨密度呈正相关，并且在男性和女性亚组中都观察到了类似的结果。GWGEIS 鉴定了 261 个全基因组显着的 ( P  < 5.00 × 10 ^-8 ) SNP × 尿酸盐相互作用对股骨总 BMD 的影响（NOTCH4中的 rs8192585，PBX1中的 rs116080577 ，COL5A1 中的rs9409991），17 个全基因组显着的 SNP × 尿酸盐相互作用效应脚后跟 BMD（PDE11A 中的rs145344540和 DKK2 中的rs78485379 ）， L1-L4 BMD 的17 个提示性全基因组 SNP × 尿酸盐相互作用效应（P  < 1.00 × 10 ^{-5 ）（PTPRD 中的}rs10977015）。我们还检测到男性和女性亚组中 BMD 的全基因组显着和暗示性 SNP × 尿酸盐相互作用效应。

结论

本研究报道了几个新的候选基因，并加强了基因与尿酸盐相互作用对骨密度变化的影响的证据。