Dose-response relationship between alcohol drinking and gout risk: do subtypes of alcoholic beverages make a difference?

OBJECTIVE: Although previous studies have explored the association of drinking with gout risk, the dose-response relationship was uncertain and the evidence between subtypes of alcoholic beverages and gout risk was limited. METHODS: The weekly alcoholic beverage consumption in the United Kingdom Biobank (UKB) was collected and calculated. The Cox regression model was applied to assess the impact of alcohol drinking and its subtypes on gout risk by calculating the hazard ratio (HR) and 95% confidence interval (CI). Besides, the restricted cubic splines were used to estimate the dose-response relationship between alcoholic drinking and gout risk. To evaluate the robustness, we performed subgroup analysis across various demographic characteristics. RESULTS: During a mean follow-up period of 11.70 years, a total of 5,728 newly incident gout cases were diagnosed among 331,865 participants. We found that light alcohol drinking was linked to a slight decrease in gout incidence among females (HR, 0.78; 95% CI, 0.65 to 0.94, P=0.01), whereas it showed no significant association in males. Moreover, the dose-response relationship showed that light red wine and fortified wine could reduce the gout risk, while beer, champagne plus white wine and spirits promoted the gout risk at any dose. CONCLUSION: Our study suggested a J-shaped dose-response relationship of drinking with gout risk in females rather than males. For specific alcoholic beverages, light consumption of red wine and fortified wine was associated with reduced gout risk. These findings offer new insights into the roles of alcoholic beverages in gout, while further validation is warranted.

Lifestyle and genetic predisposition are associated with incident irritable bowel syndrome: A population-based prospective cohort study.

Few prospective studies have investigated the joint effect of lifestyle factors and genetic susceptibility on the risk of irritable bowel syndrome (IBS). This study aims to evaluate the associations of lifestyle and genetic factors with incident IBS in the UK Biobank. We analyzed data from 481,057 participants (54% female) without prevalent IBS at enrollment in the UK Biobank. An overall healthy lifestyle was defined using six modifiable lifestyle factors, including smoking, body mass index (BMI), sleep duration, diet, physical activity, and alcohol consumption, and hence categorized into 'favorable', 'intermediate', and 'unfavorable' lifestyles. A Cox proportional hazard model was used to investigate the association between a healthy lifestyle and incident IBS. Furthermore, we constructed a polygenic risk score (PRS) for IBS and assessed whether lifestyle modified the effect of genetics on the development of IBS. During a median follow-up of 12.1 years, 8645 incident IBS were ascertained. Specifically, among the six modifiable lifestyle factors, adequate sleep demonstrates the greatest protective effect (hazard ratio [HR]: 0.72, 95% CI: 0.69,0.75) against IBS. Compared with a favorable lifestyle, an unfavorable lifestyle was associated with a 56% (95% CI: 46%-67%) increased risk of IBS (P = 8.99 × 10-40). The risk of incident IBS was 12% (95% CI: 4%-21%) higher among those at high genetic risk compared with those at low genetic risk (P = 0.005). When considering the joint effect of lifestyle and genetic susceptibility, the HR nearly doubled among individuals with high genetic risk and unfavorable lifestyle (HR: 1.80; 95% CI:1.51-2.15; P = 3.50 × 10-11) compared to those with low genetic risk and favorable lifestyle. No multiplicative or addictive interaction was observed between lifestyle and genetics. The findings from this study indicated that lifestyle and genetic factors were independently associated with the risk of incident IBS. All these results implicated a possible clinical strategy of lowering the incidence of IBS by advocating a healthy lifestyle.

Air pollutants, genetic susceptibility, and the risk of incident gastrointestinal diseases: A large prospective cohort study.

A comprehensive overview of the associations between air pollution and the risk of gastrointestinal (GI) diseases has been lacking. We aimed to examine the relationships of long-term exposure to ambient particulate matter (PM) with aerodynamic diameter ≤2.5 µm (PM2.5), 2.5-10 µm (PMcoarse), ≤10 µm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), with the risk of incident GI diseases, and to explore the interplay between air pollution and genetic susceptibility. A total of 465,703 participants free of GI diseases in the UK Biobank were included at baseline. Land use regression models were employed to calculate the residential air pollutants concentrations. Cox proportional hazard models were used to evaluate the associations of air pollutants with the risk of GI diseases. The dose-response relationships of air pollutants with the risk of GI diseases were evaluated by restricted cubic spline curves. We found that long-term exposure to ambient air pollutants was positively associated with the risk of peptic ulcer (PM2.5 : Q4 vs. Q1: hazard ratio (HR) 1.272, 95% confidence interval (CI) 1.179-1.372, NO2: 1.220, 1.131-1.316, and NOx: 1.277, 1.184-1.376) and chronic gastritis (PM2.5: 1.454, 1.309-1.616, PM10 : 1.232, 1.112-1.366, NO2: 1.456, 1.311-1.617, and NOx: 1.419, 1.280-1.574) after Bonferroni correction. Participants with high genetic risk and high air pollution exposure had the highest risk of peptic ulcer, compared to those with low genetic risk and low air pollution exposure (PM2.5: HR 1.558, 95%CI 1.384-1.754, NO2: 1.762, 1.395-2.227, and NOx: 1.575, 1.403-1.769). However, no significant additive or multiplicative interaction between air pollution and genetic risk was found. In conclusion, long-term exposure to ambient air pollutants was associated with increased risk of peptic ulcer and chronic gastritis.

Metabolic Syndrome Is Associated With an Increased Risk of Rheumatoid Arthritis: A Prospective Cohort Study Including 369,065 Participants.

OBJECTIVE: To explore the associations between metabolic syndrome (MetS) and its individual components and the risk of rheumatoid arthritis (RA). METHODS: A total of 369,065 individuals were included in the present study based on the UK Biobank. Multivariable Cox proportional hazards regression models were applied to estimate the associations between MetS and its individual components and the risk of RA. Mediation analysis was performed to further assess the potential mediating role of C-reactive protein (CRP) in the relationship between MetS and RA. RESULTS: During a median follow-up period of 12.04 years, a total of 4901 incident RA cases were documented. MetS (hazard ratio [HR] 1.22, 95% CI 1.14-1.30) and 4 of its 5 components (elevated waist circumference [WC; HR 1.21, 95% CI 1.12-1.32], elevated triglyceride [TG] level [HR 1.12, 95% CI 1.05-1.19], reduced high-density lipoprotein cholesterol [HDL-C] level [HR 1.31, 95% CI 1.23-1.39], and hyperglycemia [HR 1.15, 95% CI 1.05-1.25]) were associated with an increased risk of RA. In addition, the risk of RA increased as the number of diagnosed MetS components increased, with the highest risk in participants with all 5 components. Mediation analysis showed that CRP might mediate the association between MetS and RA, accounting for 9.27% of the total effect. CONCLUSION: These findings indicated positive associations between MetS and 4 of its components (WC, TG, HDL-C, and hyperglycemia) and the risk of RA, highlighting the importance of MetS management in the prevention of RA.

Air Pollution and Allergic Rhinitis: Findings from a Prospective Cohort Study.

To investigate the association of long-term exposure to ambient air pollution with the risk of allergic rhinitis (AR), we performed a longitudinal analysis of 379,488 participants (47.4% women) free of AR at baseline in the UK Biobank. The annual average concentrations of PM2.5, PMcoarse, PM10, NO2, and NOx were estimated by land use regression models. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). A weighted polygenic risk score was constructed. During a median follow-up period of 12.5 years, 3095 AR cases were identified. We observed significant associations between the risk of AR and PM2.5 (HR: 1.51, 95% CI: 1.27-1.79, per 5 µg/m3), PMcoarse (HR: 1.28, 95% CI: 1.06-1.55, per 5 µg/m3), PM10 (HR: 1.45, 95% CI: 1.20-1.74, per 10 µg/m3), NO2 (HR: 1.14, 95% CI: 1.09-1.19, per 10 µg/m3), and NOx (HR: 1.10, 95% CI: 1.05-1.15, per 20 µg/m3). Moreover, participants with high air pollution combined with high genetic risk showed the highest risk of AR, although no multiplicative or additive interaction was observed. In conclusion, long-term exposure to air pollutants was associated with an elevated risk of AR, particularly in high-genetic-risk populations, emphasizing the urgent need to improve air quality.

Genetically predicted iron status was associated with the risk of prostate cancer.

Introduction: Observational studies have reported a relationship between iron status and the risk of prostate cancer. However, it remains uncertain whether the association is causal or due to confounding or reverse causality. To further clarify the underlying causal relationship, we conducted a Mendelian randomization (MR) analysis. Methods: We selected three genetic variants (rs1800562, rs1799945, and rs855791) closely correlated with four iron status biomarkers (serum iron, log-transformed ferritin, transferrin saturation, and transferrin) as instrumental variables. Summary statistics for prostate cancer were obtained from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium including 79,148 cases and 61,106 controls of European ancestry. The inverse-variance weighted (IVW) method was conducted primarily to estimate the association of genetically predicted iron status and the risk of prostate cancer, supplemented with simple-median, weighted-median and maximum-likelihood methods as sensitivity analysis. MR-Egger regression was used to detect directional pleiotropy. We also conducted a meta-analysis of observational studies to assess the associations between iron status and the risk of prostate cancer. Results: Genetically predicted increased iron status was associated with the decreased risk of prostate cancer, with odds ratio of 0.91 [95% confidence interval (CI): 0.84, 0.99; P = 0.035] for serum iron, 0.81 (95% CI: 0.65, 1.00; P = 0.046) for log- transformed ferritin, 0.94 (95% CI: 0.88, 0.99; P = 0.029) for transferrin saturation, and 1.15 (95% CI: 0.98, 1.35; P = 0.084) for transferrin (with higher transferrin levels representing lower systemic iron status), using the inverse-variance weighted method. Sensitivity analyses produced consistent associations, and MR-Egger regression indicated no potential pleiotropy. Our replication analysis based on FinnGen research project showed compatible results with our main analysis. Results from our meta-analysis similarly showed that serum ferritin [standardized mean difference (SMD): -1.25; 95% CI: -2.34, -0.16; P = 0.024] and transferrin saturation (SMD: -1.19; 95% CI: -2.34, -0.05; P = 0.042) were lower in patients with prostate cancer compared with that in controls. Discussion: Our study suggests a protective role of iron in the risk of prostate cancer, further investigations are required to clarify the underlying mechanisms.