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Mendelian randomization study of serum uric acid levels and diabetes risk: evidence from the Dongfeng-Tongji cohort.

ABSTRACT: Limited Mendelian randomization (MR) studies have assessed the causal relationship between serum uric acid levels and diabetes risk. Here we investigated causality between the serum uric acid concentration and diabetes risk in Chinese population. The observational analysis, based on the Dongfeng-Tongji prospective cohort (n=15 195) we tested the association of serum uric acid levels with incident diabetes risk. In the instrumental variable analysis, we examined the association of the genetic risk score (GRS) of serum uric acid with diabetes risk in case-control design (2539 cases and 4595 controls) via MR analysis. During a mean (SD) follow-up of 4.5 (0.5) years, 1156 incident diabetes cases were identified. Compared with those in the lowest quintile of serum uric acid levels, the HRs of incident diabetes were 1.19 (95% CI 0.96 to 1.48), 1.12 (95% CI 0.90 to 1.40), 1.38 (95% CI 1.12 to 1.70), and 1.51 (95% CI 1.23 to 1.87) for Q2, Q3, Q4 and Q5, respectively (P-trend <0.001). The GRS was strongly associated with serum uric acid levels (β=0.17, 95% CI 0.15 to 0.19; P=2.81×10-67). However, no significant association was observed between the GRS and diabetes risk (OR=1.01, 95 CI 0.95 to 1.06; P=0.75). Even though serum uric acid levels were significantly associated with increased incident diabetes risk, the results did not provide evidence for a causal relationship between them.

SUBMITTER: Keerman M

PROVIDER: S-EPMC7050304 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Mendelian randomization study of serum uric acid levels and diabetes risk: evidence from the Dongfeng-Tongji cohort.

Keerman Mulatibieke M Yang Fen F Hu Hua H Wang Jing J Wang Fei F Li Zhaoyang Z Yuan Jing J Yao Ping P Zhang Xiaomin X Guo Huan H Yang Handong H He Meian M

BMJ open diabetes research & care 20200201 1

<h4>Objective</h4>Limited Mendelian randomization (MR) studies have assessed the causal relationship between serum uric acid levels and diabetes risk. Here we investigated causality between the serum uric acid concentration and diabetes risk in Chinese population.<h4>Research design and methods</h4>The observational analysis, based on the Dongfeng-Tongji prospective cohort (n=15 195) we tested the association of serum uric acid levels with incident diabetes risk. In the instrumental variable ana ...[more]

PMID: 32111716

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Project description:ObjectiveThe effects of coffee consumption on serum uric acid (SUA) levels and gout risk are controversial. There have hitherto been no reports based on Mendelian randomization (MR) analysis of its effects that consider pleiotropy. Here, we evaluated the effects of coffee consumption across ancestry populations, taking pleiotropy into account.MethodsWe performed the first MR analyses for coffee consumption on SUA levels and gout, considering pleiotropy. We used the following summary statistics of genome-wide association studies from a Japanese population: habitual coffee consumption (152,634 subjects), gout (3053 cases and 4554 controls), and SUA levels (121,745 subjects). In addition to fixed-effect inverse variance weighted (IVW) meta-analysis, we performed a robust evaluation of heterogeneity and removed several instruments for reasons of possible pleiotropy. Previous European datasets were also reevaluated while heterogeneity was considered.ResultsHabitual coffee consumption was significantly and inversely associated with gout (odds ratio [OR] = 0.29, 95% confidence interval [95% CI]: 0.16-0.51, P = 1.9 × 10-5 ) in random-effect IVW (Phet = 5.5 × 10-19 ). Excluding pleiotropic instruments, the protective effect on gout was confirmed in fixed-effect IVW analysis (OR = 0.75, 95% CI: 0.58-0.97, P = 0.026) without heterogeneity (Phet = 0.39). However, we observed no significance in the previous European datasets when heterogeneity was considered. Associations were not observed between coffee consumption and SUA levels in either ancestry in MR analyses that considered pleiotropy. Multivariable MR analysis showed that increased coffee consumption significantly reduced gout risk, even after adjusting for SUA levels (OR = 0.50, 95% CI: 0.31-0.81, P = 0.0046).ConclusionWith pleiotropy taken into account, our MR analyses revealed that coffee consumption can causally reduce gout risk, and that it may reduce gout risk independently of SUA levels.

Project description:AimsSerum uric acid (SUA) levels have been previously linked to a higher risk of cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D) according to various observational studies. However, whether this association is causally linked or simply influenced by confounding factors is unclear. Therefore, this study utilized Mendelian randomization (MR) analysis to explore the causality between SUA levels and the risk of CVD in individuals with T2D.MethodsOur study cohort consisted of 5723 participants who were diagnosed with T2D in the National Health and Nutrition Examination Survey (NHANES) from 1999-2018. The study assessed the association between SUA levels and the risk of CVD using a multivariable logistic regression model. To further examine causality between SUA levels and CVD, a two-sample MR study was conducted utilizing genetic data from genome-wide association studies (GWAS) involving over 140,000 individuals. The main MR analysis employed the inverse-variance-weighted (IVW) method. Additionally, several sensitivity analyses were performed to evaluate the robustness and pleiotropy of the results.ResultsIn the cross-sectional study, after multivariable adjustment, participants with SUA levels >6.7 mg/dL exhibited odds ratios (ORs) of 1.51 (95% CI: 1.01-2.26, p=0.049) for heart failure, 1.02 (95% CI: 0.69-1.50, p=0.937) for coronary heart disease, 1.36 (95% CI: 0.78-2.38, p=0.285) for angina, and 1.22 (95% CI: 0.80-1.85, p=0.355) for myocardial infarction when compared to participants with SUA levels ≤ 4.6 mg/dL. However, in the IVW analysis, no causality between SUA levels and the risk of heart failure was observed (OR = 1.03, 95% CI: 0.97-1.09, p = 0.293). The secondary analysis yielded similar results (OR = 1.05, 95% CI: 0.96-1.14, p = 0.299). The sensitivity analyses further supported our primary findings.ConclusionBased on the MR study, we did not find supporting evidence for a causal association between SUA levels and the risk of heart failure.

Dataset Information

Mendelian randomization study of serum uric acid levels and diabetes risk: evidence from the Dongfeng-Tongji cohort.

Publications

Mendelian randomization study of serum uric acid levels and diabetes risk: evidence from the Dongfeng-Tongji cohort.

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