A mendelian randomization analysis: The causal association between serum uric acid and atrial fibrillation

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numbere13300
JournalEuropean Journal of Clinical Investigation
Volume50
Issue number10
DOIs
Publication statusPublished - 2020 Oct 1

Bibliographical note

Funding Information:
This work was supported by grants [HI18C0070 to P H-N] and [HI19C0114 to P H-N] from the Ministry of Health and Welfare, a grant [NRF-2017R1A2B4003983 to P H-N] from the Basic Science Research Program run by the National Research Foundation of Korea funded by the Ministry of Science and ICT and a grant [NRF-2019R1I1A1A01041440 to H.M] from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education. We would like to thank Mr. John Martin for his linguistic assistance. This study was conducted with bioresources from National Biobank of Korea, the Center for Disease Control and Prevention, Republic of Korea. (KBN-2016-005).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry

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