孟德尔随机化
医学
内科学
心脏病学
混淆
优势比
心房颤动
置信区间
胃肠病学
全基因组关联研究
尿酸
单核苷酸多态性
基因型
生物
遗传学
基因
遗传变异
作者
Myunghee Hong,Je‐Wook Park,Pil‐Sung Yang,Inseok Hwang,Tae‐Hoon Kim,Hee Tae Yu,Jae‐Sun Uhm,Boyoung Joung,Moon‐Hyoung Lee,Sun Ha Jee,Hui‐Nam Pak
摘要
Abstract Background Observational studies have shown that high levels of serum uric acid (UA) were associated with atrial fibrillation (AF). However, the causal effect of urate on the risk of AF is still unknown. To clarify the potential causal association between UA and AF, we performed a Mendelian randomization (MR) analysis using genetic instrumental variables (IVs). Materials and methods From the Korean GWAS dataset of 633 patients with AF (mean age 50.6 ± 7.8 years, 80.9% male, Yonsei AF Ablation cohort) who underwent radiofrequency catheter ablation and the data from 3533 controls (from the Korea Genome Epidemiology Study), we selected 9 SNPs, with a P value less than .05, associated with an increased UA serum level. Additionally, we calculated the weighted genetic risk score (wGRS) using the selected 9 SNPs, to use it as an instrumental variable. A Mendelian randomization analysis was calculated by a 2‐stage estimator method. Results The conventional association between the serum UA and AF was significant ( P = .001) after adjusting for potential confounding factors. The SNP rs1165196 on SLC17A1 (F‐statistics = 208.34, 0.18 mg/mL per allele change, P < .001) and wGRS ( F ‐statistics = 222.26, 0.20 mg/mL per 1SD change, P < .001) were significantly associated with an increase in the UA level. The MR analysis was causally associated with rs1165196 (estimated odds ratio (OR), 0.21, 95% confidence interval (CI), 0.06‐0.75, P = .017), but not wGRS (estimated OR, 1.07, 95% CI, 0.57‐2.01, P = .832). Conclusion The serum UA level was independently associated with the AF risk.
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