| 【Abstract】 Background Dementia seriously affects the quality of life and lifespan of elderly people, with Alzheimer's disease (AD) being the most common type of dementia. Previous studies have suggested that gout may reduce the risk of developing AD, but the causal relationship between the two still requires further investigation. Objective To investigate the potential causal relationship between gout and Alzheimer's disease through a two-sample Mendelian randomization analysis, so as to provide references and assistance for the prevention and treatment of AD. Methods Data were derived from Genome-Wide Association Studies (GWAS) extracted in 2024, using pooled data on gout (6,810 cases in the case group and 477,788 cases in the control group) from UK Biobank 2021 as the exposure and FinnGen AD (3,899 cases in the case group and 214,893 cases in the control group) from the same year as the outcome. Using inverse variance weighting method, MR-Egger method, weighted median method, simple model method, and weighted model method to analyze the potential causal relationship between gout and AD. The MR-Egger method was used to detect pleiotropy, Cochran’s Q test was employed to assess the heterogeneity of the results, and the leave-one-out method was applied for sensitivity analysis. A funnel plot was drawn to detect potential bias. Results The inverse variance weighting method showed a negative causal relationship between gout and AD (OR=0.004, 95% CI: 0~0.700, P<0.05). The funnel plot showed a symmetrical distribution, indicating a low likelihood of bias affecting the causal relationship. Cochran’s Q test shows that there is no heterogeneity in MR analysis between gout and AD. The MR Egger method results indicate that there is no horizontal pleiotropy among the instrumental variables of gout. The reverse MR analysis of gout and AD showed no reverse causal relationship between gout and AD. Conclusion There is a negative causal relationship between gout and AD, with gout potentially reducing the risk of AD. |