Department of Rheumatology, Korea University College of Medicine, Seoul, Korea.
Eur J Clin Invest. 2019 Sep;49(9):e13156. doi: 10.1111/eci.13156. Epub 2019 Jul 31.
This study aimed to examine whether the uric acid level or gout is causally associated with bone mineral density (BMD).
We performed a two-sample Mendelian randomization (MR) analysis. The statistics dataset, we used was from a meta-analysis of genome-wide association studies (GWASs) on uric acid levels from 14 studies with a total of 28 141 participants of European descent, and the dataset for gout from the United Kingdom (UK) Biobank (4807 cases and 3 32 352 controls). We further used the summary statistics dataset of a GWAS on lumbar spine and femur neck (FN) BMDs of individuals of European ancestry (up to 32 735).
The instrumental variables (IVs) selected were six single nucleotide polymorphisms (SNPs) from the uric acid level GWAS data and 19 SNPs from the gout GWAS data. The inverse-variance weighted (IVW) method yielded no evidence to support a causal association between the uric acid level or gout and lumbar spine BMD (β = -.002, standard error (SE) = 0.035, P = .951; β = -.700, SE = 0.672, P = .297). MR-Egger regression revealed no causality between uric acid level, gout and lumbar spine. Similarly, the weighted median approach provided no evidence of causality between uric acid level, gout and lumbar spine BMD. The MR results on FN BMD showed similar patterns with those of the lumbar spine BMD.
Mendelian randomization analysis did not support a causal association between uric acid level, gout and lumbar spine or FN BMD.
本研究旨在探讨血尿酸水平或痛风是否与骨密度（BMD）有因果关系。
我们进行了两样本孟德尔随机化（MR）分析。我们使用的统计数据集来自 14 项关于血尿酸水平的全基因组关联研究（GWAS）的荟萃分析，共纳入了 28141 名欧洲血统的参与者，痛风数据集来自英国生物银行（4807 例病例和 332352 例对照）。我们进一步使用了欧洲血统个体腰椎和股骨颈（FN）BMD 的 GWAS 汇总统计数据集（多达 32735 人）。
所选的工具变量（IVs）是来自血尿酸水平 GWAS 数据的 6 个单核苷酸多态性（SNPs）和来自痛风 GWAS 数据的 19 个 SNPs。逆方差加权（IVW）法没有证据支持血尿酸水平或痛风与腰椎 BMD 之间存在因果关系（β=-.002，标准误差（SE）=0.035，P=0.951；β=-.700，SE=0.672，P=0.297）。MR-Egger 回归显示血尿酸水平、痛风与腰椎之间不存在因果关系。同样，加权中位数方法也没有提供血尿酸水平、痛风与腰椎 BMD 之间存在因果关系的证据。尿酸水平、痛风与 FN BMD 之间的 MR 结果也呈现出与腰椎 BMD 相似的模式。
孟德尔随机化分析不支持血尿酸水平、痛风与腰椎或 FN BMD 之间存在因果关系。
