[Causal relationship between genetically determined childhood obesity and serum uric acid levels and gout in adults:...

Obesity is a significant risk factor for developing hyperuricemia and gout. This study aims to exploring the causal relationship between childhood obesity and serum uric acid (SUA) levels and gout in adults in a Mendelian randomization (MR) framework. The Genome-wide association study (GWAS) data for childhood obesity were obtained from the Early Growth Genetics Consortium, published in 2012, involving 13 848 children. The GWAS data for SUA were sourced from a 2021 phenome-wide association study in the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) GWAS database, comprising 343 836 adult participants. The GWAS data for gout were derived from summary statistics of European populations in the Global Urate Genetics Consortium (GUGC) database, published in 2013, involving 69 374 adult individuals. A two-sample MR was conducted to investigate whether childhood obesity is causally associated with SUA levels and gout in adults respectively. Single-nucleotide polymorphisms (SNPs) significantly associated with childhood obesity were used as instrumental variables. Inverse-variance weighted (IVW) analysis, weighted-median analysis, and MR-Egger regression were conducted in this MR analysis. Sensitivity analyses by using leave-one-out method were conducted to confirm the accuracy and robustness of the results. The results showed that a total of 13 848 European participants involved of childhood obesity (defined as ≥95th percentile of body mass index, 5 530 cases vs. 8 318 controls) from a summary dataset was included. MR analysis showed that genetically determined childhood obesity is positively associated with the level of SUA (IVW method: β=0.02, 95%CI: 0.01-0.03, P=0.015 9) and increased the risk of gout (IVW method: OR=1.19, 95%CI: 1.06-1.34, P=0.003). In conclusion, the causal effects of genetically determined childhood obesity on SUA levels and gout in adults was founded in this study, indicating that childhood obesity is a potential risk factor for hyperuricemia and gout.