Background Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is highly correlated with serum uric acid (SUA). However, these studies have an inherent risk of bias due to reverse causality. Here, we perform a Mendelian randomization (MR) study to investigate causality between SUA and NAFLD. Methods We performed a two-sample bidirectional MR analysis using summary-level data from genome-wide association studies (GWAS) of SUA (with up to 110,347 individuals) and NAFLD (1483 cases and 17781 controls) in European populations. First, 13 single nucleotide polymorphisms (SNPs) associated with SUA were selected as instruments to estimate the causal effect of elevated SUA levels on the risk of NAFLD using the inverse-variance weighted (IVW) method. Then we performed MR with 3 SNPs as genetic instruments for NAFLD. To test the reliability, further sensitivity analyses were also conducted. Results Our MR analyses demonstrated that NAFLD was associated with SUA levels (β = 0.032, p = 0.003). Similar results were obtained using other MR methods and in sensitivity analyses. Genetic predisposition to elevated SUA levels was not associated with NAFLD (IVW MR, odds ratio (OR) = 1.02, 95% CI: 0.90-1.15, p = 0.775). Similar results were obtained using other 4 pleiotropy robust MR methods and in sensitivity analyses excluding 9 SNPs associated with potential confounders. Conclusions Our study supports the causal increased SUA levels by NAFLD, while our study does not confirm a causal association for serum uric acid levels on risk of NAFLD. Further study is needed to interpret the potential mechanisms.

Objectives: The purpose of this meta-analysis was to assess whether there is an association between hypothyroidism and the risk of cognitive dysfunction. Methods: PubMed, Cochrane Library, and Embase were searched for relevant studies published from database inception to 4 May 2022, using medical subject headings (MeSHs) and keywords. Results: Eight studies involving 1,092,025 individuals were included, published between 2010 and 2021. The pooled analysis showed that there was no association between hypothyroidism and cognitive dysfunction (OR = 1.13, 95% CI = 0.84–1.51, p = 0.426), including both all-cause dementia (OR = 1.04, 95% CI = 0.76–1.43, p = 0.809) and cognitive impairment (OR = 1.50, 95% CI = 0.68–3.35, p = 0.318). Neither overt hypothyroidism (OR = 1.19, 95% CI = 0.70–2.02, p = 0.525) nor subclinical hypothyroidism (OR = 1.04, 95% CI = 0.73–1.48, p = 0.833) was associated with cognitive dysfunction. Neither prospective cohort (OR = 1.08, 95% CI = 0.77–1.51, p = 0.673) nor cross-sectional studies (OR = 1.23, 95% CI = 0.63–2.42, p = 0.545) had any effect on the association. Interestingly, the risk of cognitive dysfunction was significantly increased in the group not adjusted for vascular comorbidity (OR = 1.47, 95% CI = 1.07–2.01, p = 0.017), while it was reduced in the adjusted group (OR =0.82, 95% CI = 0.79–0.85, p < 0.001). Conclusions: This meta-analysis shows that hypothyroidism was associated with a reduced risk of cognitive dysfunction after adjustment for vascular-disease comorbidities. More prospective observational studies are needed in the future to investigate the relationship between hypothyroidism and cognitive dysfunction.

Aims/IntroductionThe hemoglobin glycation index (HGI) represent the disparity between actual glycated hemoglobin measurements and predicted HbA1c. It serves as a proxy for the degree of non‐enzymatic glycation of hemoglobin, which has been found to be positively correlated with diabetic comorbidities. In this study, we investigated the relationship between HGI and non‐alcoholic fatty liver disease (NAFLD), along with other relevant biological markers in patients with diabetes.Materials and MethodsThis cross‐sectional study consisted of 3,191 adults diagnosed with type 2 diabetes mellitus. We calculated the predicted glycated hemoglobin levels based on fasting blood glucose levels. Multivariate binary logistic regression analysis was conducted to examine the correlation between the HGI and NAFLD. Hepatic steatosis was diagnosed using ultrasonography.ResultsAmong all participants, 1,784 (55.91%) were diagnosed with NAFLD. Participants with confirmed NAFLD showed elevated body mass index, diastolic blood pressure, liver enzyme, total cholesterol, triglyceride, low‐density lipoprotein and uric acid levels compared with those without NAFLD. In the unadjusted model, participants in the last tertile of HGI were 1.40‐fold more likely to develop NAFLD than those in the first tertile (95% confidence interval 1.18–1.66; P < 0.001). In the fully adjusted model, those in the last tertile of HGI had a 39% increased risk of liver steatosis compared with confidence interval in the first tertile of HGI (95% confidence interval 1.12–1.74; P < 0.001).ConclusionsA higher HGI suggests an elevated risk of developing NAFLD in patients with type 2 diabetes.