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Background: Observational studies have demonstrated the alterations of gut microbiota composition in diabetic nephropathy (DN), however, the correlation between gut microbiota and DN remains unclear. Methods: A two-sample Mendelian randomization (MR) analysis was designed to estimate the association between gut microbiota and DN. The summary statistics of gut microbiota from phylum level to genus level were obtained from a large-scale, genome-wide association study involving 18,340 individuals, and the data at the species level was derived from the study of TwinsUK Registry, including 1126 twin pairs. The summary statistics of DN were originated from the latest release data of FinnGen (R7, 299623 participants). The MR estimation was calculated using inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was assessed using Cochrane's Q test. Results: Inverse variance weighted results indicated that the order Bacteroidetes and its corresponding class and phylum [odds ratio (OR), 1.58; 95% confidence interval (CI), 1.15–2.17], the family Verrucomicrobiaceae and its corresponding class and order (OR, 1.46; 95% CI, 1.14–1.87), the genera Akkermansia (OR, 1.46; 95% CI, 1.14–1.87) and Catenibacterium (OR, 1.33; 95% CI, 1.07–1.66) might be associated with a higher risk of DN; whereas the genera Coprococcus2 (OR, 0.68; 95% CI, 0.51–0.91) and Eubacterium_coprostanoligenes_group (OR, 0.69; 95% CI, 0.52–0.92) might play protective roles in DN. Conclusions: This MR study suggested that several gut bacteria were potentially associated with DN, further studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Various facial colour cues were identified as valid predictors of facial attractiveness, yet the conventional univariate approach has simplified the complex nature of attractiveness judgement for real human faces. Predicting attractiveness from colour cues is difficult due to the high number of candidate variables and their inherent correlations. Using datasets from Chinese subjects, this study proposed a novel analytic framework for modelling attractiveness from various colour characteristics. One hundred images of real human faces were used in experiments and an extensive set of 65 colour features were extracted. Two separate attractiveness evaluation sets of data were collected through psychophysical experiments in the UK and China as training and testing datasets, respectively. Eight multivariate regression strategies were compared for their predictive accuracy and simplicity. The proposed methodology achieved a comprehensive assessment of diverse facial colour features and their role in attractiveness judgements of real faces; improved the predictive accuracy (the best-fit model achieved an out-of-sample accuracy of 0.66 on a 7-point scale) and significantly mitigated the issue of model overfitting; and effectively simplified the model and identified the most important colour features. It can serve as a useful and repeatable analytic tool for future research on facial impression modelling using high-dimensional datasets. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association between glycated haemoglobin (HbA1c) levels and chronic obstructive pulmonary disease (COPD) incidents in the general population, and the association between HbA1c levels and mortality in patients with COPD. Materials and Methods: We investigated the association of HbA1c levels with COPD risk in the general population in the UK Biobank, using data from 420 065 participants. Survival analysis was conducted for 18 854 patients with COPD. We used restricted cubic spline analysis to assess the dose‐response relationship between HbA1c levels and COPD risk and survival. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: During a median follow‐up of 12.3 years, 11 556 COPD cases were recorded. HbA1c had a non‐linear relationship with COPD risk (p for non‐linearity <.05). Compared with the quintile 2 (32.2‐<34.3 mmol/mol), those with HbA1c levels above 38.7 mmol/mol (quintile 5) had a 22% (HR, 1.22, 95% CI: 1.15‐1.30) higher risk of COPD. Compared with the HbA1c decile 2 (30.5‐<32.2 mmol/mol), the HRs (95% CI) of COPD risk were 1.16 (1.03‐1.30) and 1.36 (1.24‐1.50) in the lowest HbA1c decile (<30.5 mmol/mol) and highest decile (≥41.0 mmol/mol), respectively. The increased COPD risk associated with HbA1c was more pronounced in younger, current smokers, passive smokers, and participants with a higher Townsend deprivation index (all p for interaction <.05). Among patients with COPD, 4569 COPD cases died (488 because of COPD) during a median follow‐up of 5.4 years. Regarding COPD survival, HbA1c had a non‐linear relationship with all‐cause death (p for non‐linearity <.05). Those with HbA1c quintile 5 (≥38.7 mmol/mol) had a 23% (HR, 1.23, 95% CI: 1.10‐1.37) higher risk of all‐cause death compared with the quintile 2 (32.2‐<34.3 mmol/mol). Compared with the HbA1c decile 4 (33.3‐<34.3 mmol/mol), those in the lowest HbA1c decile (<30.5 mmol/mol) and highest HbA1c decile (≥41.0 mmol/mol) had 22% (HR, 1.22; 95% CI: 1.01‐1.47) and 28% (HR, 1.28; 95% CI: 1.11‐1.48) higher risk for overall death. However, no significant association was observed between HbA1c levels and the risk of COPD‐specific death. Conclusions: Our findings indicated that lower and higher HbA1c levels were associated with a higher risk of COPD. In COPD cases, lower and higher HbA1c levels were associated with a higher COPD all‐cause death risk. [ABSTRACT FROM AUTHOR]

Aim: To investigate the associations of diabetes, prediabetes and diabetes duration with chronic obstructive pulmonary disease (COPD) risk and survival in the UK Biobank. Materials and Methods: We conducted a prospective analysis among 452 680 participants without COPD at baseline using UK Biobank data. Multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox regression models. The dose–response relationship was explored using restricted cubic splines. A separate survival analysis was conducted for 12 595 patients with incident COPD. Results: Over a median follow‐up of 12.3 years, 12 595 cases of COPD were documented. Compared with the reference group, those with prediabetes and diabetes were associated with an 18% (HR 1.18 [95% CI: 1.13‐1.24]) and 35% (HR 1.35 [95% CI: 1.24‐1.47]) higher risk of COPD, respectively. Diabetes duration was associated with COPD risk, with multivariable HRs (95% CIs) of 1.23 (1.05‐1.44), 1.20 (1.04‐1.39) and 1.18 (1.01‐1.37) for diabetes duration of 7 years or longer, 3 to less than 7 years, and 1 to less than 3 years versus less than 1 year, respectively. Dose–response analysis revealed a non‐linear relationship between diabetes duration and COPD risk. Regarding COPD survival, COPD patients with prediabetes and diabetes had a 9% (HR 1.09 [95% CI: 1.00‐1.19]) and 21% (HR 1.21 [95% CI: 1.05‐1.41]) higher risk of overall death, respectively. Compared with the cases with a diabetes duration of less than 1 year, those with a diabetes duration of 7 years or longer were associated with a 46% higher risk of overall death (HR 1.46 [95% CI: 1.11‐1.92]). Conclusions: Our findings indicate that diabetes, prediabetes and a longer diabetes duration are associated with a higher risk of and worse survival for COPD. Future studies are warranted to determine the optimal way of diabetes control that might reduce COPD risk. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence for a potential link between air pollution and rheumatoid arthritis (RA) is inconsistent, and the modified effect of genetic susceptibility on the relationship between air pollution and RA has not been well studied. OBJECTIVE: Using a general population cohort from the UK Biobank, this study aimed to investigate the associations between various air pollutants and the risk of incident RA and to further estimate the impact of combined exposure to ambient air pollutants on the risk of developing RA under the modification effect of genetic predisposition. METHODS: A total of 342,973 participants with completed genotyping data and who were free of RA at baseline were included in the study. An air pollution score was constructed by summing the concentrations of each pollutant weighted by the regression coefficients with RA from single-pollutant models to assess the combined effect of air pollutants, including particulate matter (PM) with diameters ≤ 2.5 µm (PM2.5), between 2.5 and 10 µm (PM2.5–10), and ≤ 10 µm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). In addition, the polygenic risk score (PRS) of RA was calculated to characterize individual genetic risk. The Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of associations of single air pollutant, air pollution score, or PRS with incident RA. RESULTS: During a median follow-up time of 8.1 y, 2,034 incident events of RA were recorded. The HRs (95% CIs) of incident RA per interquartile range increment in PM2.5, PM2.5-10, PM10, NO2, and NOx were 1.07 (1.01, 1.13), 1.00 (0.96, 1.04), 1.01 (0.96, 1.07), 1.03 (0.98, 1.09), and 1.07 (1.02, 1.12), respectively. We also found a positive exposure-response relationship between air pollution score and RA risk (푝Trend = 0.000053). The HR(95% CI) of incident RA was 1.14 (1.00, 1.29) in the highest quartile group compared with the lowest quartile group of the air pollution score. Furthermore, the results of the combined effect of air pollution score and PRS on the RA risk showed that the risk of RA incidence in the highest genetic risk and air pollution score group was almost twice that of the lowest genetic risk and air pollution score group [incidence rate (IR) per 100,000 person-years: 98.46 vs. 51.19, and HR= 1.73 (95% CI: 1.39, 2.17) vs. 1 (reference)], although no statistically significant interaction between the air pollution and genetic risk for incident RA was found (푝Interaction >0.05). DISCUSSION: The results revealed that long-term combined exposure to ambient air pollutants might increase the risk of RA, particularly in those with high genetic risk. [ABSTRACT FROM AUTHOR]

Numerous observational studies have previously reported an association between inflammatory cytokines and tuberculosis (TB). However, the causal relationship between these factors remains unclear. Consequently, we conducted two-sample Mendelian randomization (MR) analyses to ascertain the causal link between levels of inflammatory cytokines and the risk of TB. Single nucleotide polymorphisms (SNPs) robustly associated with the cytokines, located in or close to their coding gene. SNP was obtained from genome-wide association studies (GWAS) of 8293 individuals of Finnish. TB data was obtained from the UK Biobank, which included 46,293 individuals of European ancestry (comprising 2277 TB cases and 46,056 controls). Two-sample, bi-directional MR analyses using inverse-variance weighted (IVW) method as the primary analysis. Followed by comprehensive sensitivity analyses to validate the robustness of results. The study showed that the causal relationship between circulating levels of interleukin (IL)-7 and risk of TB (odds ratio [ OR ] = 1.001, 95% confidence intervals [ CIs ]: 1.000, 1.003. p = 0.047). No causal associations were observed between other influencing factors and the occurrence of TB. Furthermore, the analysis revealed that TB infection exhibited negative causal associations with macrophage inflammatory protein 1 alpha ([MIP-1α], OR = 0.007, 95% CI : 0.000, 0.192. p = 0.004), IL-2 (OR = 0.014, 95% CI : 0.010, 0.427. p = 0.014), interleukin-2 receptor alpha chain([IL-2rα], OR = 0.019, 95% CI : 0.001, 0.525. p = 0.019) and basic fibroblast growth factor ([bFGF], OR = 0.066, 95% CI : 0.006, 0.700. p = 0.024). The study has illuminated the causal link between inflammatory cytokines and TB, thereby enhancing our comprehension of the potential mechanisms underlying TB pathogenesis. This discovery offers promising avenues for the identification of novel therapeutic targets in TB treatment. These insights may ultimately pave the way for more effective treatment approaches, thereby improving patient outcomes. • Numerous observational studies have previously reported an association between inflammatory cytokines and tuberculosis (TB). However, the causal relationship between these factors remains unclear. Consequently, we conducted two-sample Mendelian randomization (MR) analyses to ascertain the causal link between levels of inflammatory cytokines and the risk of TB. TB data was obtained from the FinnGen cohort and UK Biobank projects. Two-sample, bi-directional MR analyses using inverse-variance weighted method as the primary analysis. Followed by comprehensive sensitivity analyses to validate the robustness of results • The study showed that the causal relationship between circulating levels of IL-7 and risk of TB, and tuberculosis infection exhibited negative causal associations with MIP1a, IL-2, IL2rα and bFGF. The discovery offers promising avenues for the identification of novel therapeutic targets in TB treatment. • It may ultimately pave the way for more effective treatment approaches, thereby improving patient outcomes [ABSTRACT FROM AUTHOR]

Objective: To investigate the associations of circulating liver function marker levels with the risk of chronic obstructive pulmonary disease (COPD)., Methods: We leveraged the data of 372,056 participants from the UK Biobank between 2006 and 2010. The assessed circulating liver function markers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), albumin (ALB), and total protein (TP). Incident COPD was identified through linkage to the National Health Service registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: During a median follow-up period of 12.3 (interquartile range:11.4-13.2) years, we documented 10,001 newly diagnosed COPD cases. Lower levels of ALT, TBIL, ALB, and TP and higher levels of GGT and ALP were nonlinearly associated with elevated COPD risk. The HR (95% CI) for decile 10 vs. 1 was 0.92 (0.84-1.01) for ALT, 0.82 (0.75-0.89) for TBIL, 0.74 (0.67-0.81) for ALB, 0.96 (0.88-1.04) for TP, 1.45 (1.31-1.62) for GGT, and 1.31 (1.19-1.45) for ALP. Restricted cubic spline analyses suggested a U-shaped relationship between AST levels and COPD risk ( P for nonlinearity <0.05)., Conclusion: We observed that all seven circulating liver function markers were nonlinearly associated with the risk of COPD, indicating the importance of liver function in COPD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Guan, Wan, Zhu, Yu, Luo, Chen, Su, Lu, Hang, Tao, Wu, Zhou and Fan.)