Frailty and depression were linked in observational studies, but the causality remains ambiguous. We intended to explore it using Mendelian randomization (MR). We obtained frailty genome-wide association study (GWAS) data from UK Biobank and TwinGen meta-analysis, and depression GWAS data from Psychiatric Genomics Consortium (PGC) and FinnGen (respectively recorded as PD and FD). We performed univariable and multivariable-adjusted MR with adjustments for body mass index (BMI) and physical activity (PA). Frailty was significantly associated with elevated risks of PD (OR, 1.860; 95% CI, 1.439 to 2.405; P < 0.001) and FD (OR, 1.745; 95% CI, 1.193 to 2.552; P = 0.004), and depression was meanwhile a susceptible factor for frailty (PD: β, 0.146; 95% CI, 0.086 to 0.201; P < 0.001; and FD: β, 0.112; 95% CI, 0.051 to 0.174; P < 0.001). This association was robust after adjustments for BMI or PA. Our study provides evidence of the bidirectional causal association between frailty and depression from genetic perspectives.

Physical activity (PA) and sedentary behaviors (SB) have been linked to the risk of type 2 diabetes (T2DM) in observational studies; however, it is unclear whether these associations are causative or confounded. This study intends to use summary genetic data from the UK Biobank and other consortiums in conjunction with the two-sample Mendelian Randomization (MR) approach to solve this problem. The inverse variance weighted (IVW) technique was utilized as the primary analysis, with sensitivity analyses using the MR-Egger, weighted-median, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) techniques. Inverse associations between self-reported moderate PA (OR: 0.3096, 95% CI: 0.1782-0.5380) and vigorous PA (OR: 0.2747, 95% CI: 0.1390-0.5428) with T2DM risk were found, respectively. However, accelerometer-based PA measurement (average acceleration) was not associated with T2DM risk (OR: 1.0284, 95% CI: 0.9831-1.0758). The time (hours/day) spent watching TV was associated with T2DM risk (OR: 2.3490, 95% CI: 1.9084-2.8915), while the time (hours/day) spent using the computer (OR: 0.8496, 95% CI: 0.7178-1.0056), and driving (OR: 3.0679, 95% CI: 0.8448-11.1415) were not associated with T2DM risk. The sensitivity analysis revealed relationships of a similar magnitude. Our study revealed that more PA and less TV viewing were related to a decreased T2DM risk, and provided genetic support for a causal relationship between PA, TV viewing, and T2DM risk.

Few epidemiological studies have investigated the relationship between flavonoids and diabetic nephropathy (DN). Therefore, we explored the association between dietary flavonoid intake and DN among 1949 US adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2008, 2009–2010, and 2017–2018. Weighted logistic regression models demonstrated that the total flavonoid intake in the second (OR: 0.642; 95% CI: 0.456–0.906), third (OR: 0.665; 95% CI: 0.447–0.988), and the highest (OR: 0.551; 95% CI: 0.382–0.796) quantiles (versus the lowest) were associated with the decreased risk of DN. Restricted cubic spline (RCS) analyses showed that the total flavonoid intake had a negative linear association with DN (p-value for non-linearity was 0.003). Weighted quantile sum (WQS) regression analyses revealed that flavan-3-ols, flavones, and anthocyanidins were the main contributors for the combined effects of six flavonoid subclasses. Our findings suggested that higher dietary flavonoid intake was associated with a decreased risk of DN, with the greatest influence coming from flavan-3-ols, flavones, and anthocyanidins.

Gout, the most prevalent inflammatory arthritis, is becoming increasingly prevalent in the United States and across the world, and it adversely impacts people’s quality of life and their health. Few studies have focused on the relationship between daily dietary quality and gout, so the topic requires further exploration. Data were derived from the National Health and Nutrition Examination Survey 2007–2016, and the inclusion criteria of the analytic sample were (1) adults, age ≥20 years, with complete information about HEI-2015, gout, and uric acid; (2) complete information of demographics, lifestyle (BMI, smoking, drinking), and disease history [hypertension, chronic kidney disease (CKD), diabetes]. The quality of the daily diet was reflected using the Healthy Eating Index 2015 (HEI-2015). The baseline features of different groups were examined using the Scott-Rao chi-square tests, and the association between the HEI-2015 score and the risk of gout/hyperuricemia (HUA) was investigated using weighted logistic regression models. The effects of different dietary components in the HEI-2015 on reducing the risk of gout/HUA were evaluated by weighted quantile sum (WQS) regression models. After adjusting for demographic characteristics, behavioral covariates, and disease history, higher HEI-2015 scores were associated with a significantly lower risk of gout (OR: 0.878, 95% CI: 0.876–0.880) and HUA (OR: 0.978, 95% CI: 0.976–0.979) in weighted logistic regression. Dairy, whole grains, plant proteins, and added sugar contributed greatly in HEI-2015 to reducing gout risk (weights of WQS index: 42, 17.18, 16.13, and 7.93%, respectively). Dairy, total fruits, greens and beans, and plant proteins contributed greatly in HEI-2015 to reducing HUA risk (weights of WQS index: 28.9, 17.13, 16.84, and 11.39%, respectively). As the result, adherence to the American Dietary Guidelines may assist to decrease the risk of gout/HUA in American adults, and greater emphasis should be placed on dairy products, whole grains, fruits, legumes, and added sugars.