Uric acid level, gout and bone mineral density: A Mendelian randomization study

Objective: This study aimed to examine whether the uric acid level or gout is causally associated with bone mineral density (BMD). Method: 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). Results: 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. Conclusions: Mendelian randomization analysis did not support a causal association between uric acid level, gout and lumbar spine or FN BMD.