广西医学

目的基于两样本双向孟德尔随机化（MR）分析体质指数与痛风之间的因果关系。方法从IEU OpenGWAS Project数据库中获取体质指数及痛风的全基因关联研究数据集。将体质指数、痛风互为暴露因素和结局，以与暴露因素、结局显著相关的单核苷酸多态性（SNP）为工具变量。筛选工具变量后，分别采用逆方差加权（IVW）法、MR-Egger检验、加权中位数（WM）法、简单模式法及加权模式进行两样本双向MR分析，并采用异质性检验、留一法及水平多效性检验来验证结果的可靠性。结果正向MR分析中，IVW法分析结果显示体质指数与痛风的发生风险之间存在正向因果关系，体质指数每增加1个标准差，痛风的发生风险增加1.007倍（OR=1.007，P<0.05），WM法、简单模式法、加权模式亦得到类似的因果关系（OR>1，P<0.05）。反向MR分析中，IVW法分析结果显示痛风与体质指数之间存在负向因果关系，但痛风对体质指数的影响较小（OR=0.301，P<0.05），WM法、加权模式亦得到类似的因果关系（OR<1，P<0.05）。双向MR分析结果均存在异质性（P<0.05），但均不存在水平多效性（P>0.05），剔除单个SNP后MR分析结果仍然具有稳定性。结论体质指数与痛风具有双向因果关系，体质指数增加是痛风发病的危险因素，而痛风对体质指数的影响较小。

Objective To analyze the causal relation of body mass index with gout based on two⁃sample bidirectional Mendelian randomization (MR). Methods Genome⁃wide association studies data of body mass index and gout were obtained from the database of IEU OpenGWAS Project. Body mass index and gout were each other's exposure factors and outcomes, and single nucleotide polymorphism (SNP), which was significantly related to exposure factors and outcomes, was used as the instrumental variables. After screening instrumental variables, two⁃sample bidirectional MR analysis was performed by employing inverse variance weighted (IVW) method, MR⁃Egger test, weighted median (WM) method, simple mode method, and weighted mode; furthermore, reliability of results was validated by using heterogeneity test, leave⁃one⁃out method, and horizontal pleiotropy test. Results In forward MR analysis, the results of IVW method analysis revealed that there was positive causality of the occurrence risk between body mass index and gout, and for every 1 standard deviation increase in body mass index, the occurrence risk of gout increased by 1.007 times (OR=1.007, P<0.05); in addition, WM method, simple mode method and weighted mode also obtained similar causal relation (OR>1, P<0.05). In backward MR analysis, the results of IVW method analysis indicated that there was negative causality between gout and body mass index, but gout had less effect on body mass index (OR=0.301, P<0.05), and WM method, weighted mode also obtained similar causal relation (OR<1, P<0.05). The results of bidirectional MR analysis were heterogeneous (P<0.05), but there was no horizontal pleiotropy (P>0.05), and the results of MR analysis were still stable after removing single SNP. Conclusion There is bidirectional causal relation between body mass index and gout, body mass index increase is the risk factor for gout onset, whereas gout has less effect on body mass index.

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