Genetically determined serum urate levels and cardiovascular and other diseases in UK Biobank cohort: A phenome-wide mendelian randomization study

by Xue Li, Xiangrui Meng, Yazhou He, Athina Spiliopoulou, Maria Timofeeva, Wei-Qi Wei, Aliya Gifford, Tian Yang, Tim Varley, Ioanna Tzoulaki, Peter Joshi, Joshua C. Denny, Paul Mckeigue, Harry Campbell, Evropi Theodoratou BackgroundThe role of urate in cardiovascular diseases (CVDs) has been extensively investigated in observational studies; however, the extent of any causal effect remains unclear, making it difficult to evaluate its clinical relevance. Methods and findingsA phenome-wide association study (PheWAS) together with a Bayesian analysis of tree-structured phenotypic model (TreeWAS) was performed to examine disease outcomes related to genetically determined serum urate levels in 339,256 unrelated White British individuals (54% female) in the UK Biobank who were aged 40 –69 years (mean age, 56.87; SD, 7.99) when recruited from 2006 to 2010. Mendelian randomization (MR) analyses were performed to replicate significant findings using various genome-wide association study (GWAS) consortia data. Sensitivity analyses were conducted to examine possible pleiotropic effe cts on metabolic traits of the genetic variants used as instruments for urate. PheWAS analysis, examining the association with 1,431 disease outcomes, identified 13 distinct phecodes representing 4 disease groups (inflammatory polyarthropathies, hypertensive disease, circulatory disease, and metabol ic disorders) and 9 disease outcomes (gout, gouty arthropathy, pyogenic arthritis, essential hypertension, c...
Source: PLoS Medicine - Category: Internal Medicine Authors: Source Type: research