Unveiling the shared genetic architecture between testosterone and polycystic ovary syndrome.

Testosterone (T) is a critical predictor of polycystic ovary syndrome (PCOS) but the genetic overlap between T and PCOS has not been established. Here by leveraging genetic datasets from large-scale genome-wide association studies, we assessed the genetic correlation and polygenic overlap between PCOS and three T-related traits using linkage disequilibrium score regression and the bivariate causal mixture model methods. The conjunctional false discovery rate (conjFDR) method was employed to identify shared causal variants. Functional annotation of variants was conducted using FUMA. Total T and bioavailable T exhibited positive correlations with PCOS, while sex hormone-binding globulin (SHBG) showed a negative correlation. All three traits demonstrated extensive genetic overlap with PCOS, with a minimum of 68% of T-related variants influencing PCOS. The conjFDR revealed 4 to 6 causal variants within joint genomic loci shared between PCOS and T-related traits. Functional annotations suggested that these variants might impact PCOS by modulating nearby genes, such as FSHB. Our findings support the hypothesis that PCOS is significantly influenced by androgen abnormalities. Additionally, this study identified several causal variants potentially involved in shared biological mechanisms between PCOS and T regulation.

Sleep fragmentation and the risk of obesity: The Sleep Heart Health Study.

OBJECTIVE: Sleep disturbances have been recognized as a risk factor for obesity. This study used polysomnography records to investigate associations between sleep fragmentation and obesity. METHODS: Objectively measured sleep fragmentation data recorded by in-home polysomnography, including total arousal index (ArI-total), ArI in rapid eye movement (REM) sleep (ArI-REM), ArI in non-REM sleep (ArI-NREM), sleep fragmentation index, sleep efficiency (SE), and wake after sleep onset (WASO), were based on the Sleep Heart Health Study (2,835 men and 2,888 women with a mean [SD] age of 63.2 [11.2] years). Multivariable regression analyses were used to examine the relationship between sleep fragmentation and obesity. RESULTS: Multinomial logistic regression showed that participants with obesity have a significantly higher ArI-total (odds ratio [OR] 1.018; 95% CI: 1.010-1.026, p < 0.001), ArI-REM (OR 1.010; 95% CI: 1.002-1.018, p = 0.009), ArI-NREM (OR 1.017; 95% CI: 1.009-1.024, p < 0.001), and WASO (OR 1.003; 95% CI: 1.001-1.005, p = 0.007) compared with those with normal weight. Furthermore, multiple linear regression analyses showed an obvious correlation between ArI-total, ArI-REM, ArI-NREM, SE, WASO, and BMI. CONCLUSIONS: The results revealed that ArI-total, ArI-REM, ArI-NREM, SE, and WASO were associated with obesity. The improvement of sleep fragmentation may contribute to decreasing the risk of obesity.

Mendelian randomization analysis of the association between human blood cell traits and uterine polyps.

Human blood cells (HBCs) play essential roles in multiple biological processes but their roles in development of uterine polyps are unknown. Here we implemented a Mendelian randomization (MR) analysis to investigate the effects of 36 HBC traits on endometrial polyps (EPs) and cervical polyps (CPs). The random-effect inverse-variance weighted method was adopted as standard MR analysis and three additional MR methods (MR-Egger, weighted median, and MR-PRESSO) were used for sensitivity analyses. Genetic instruments of HBC traits was extracted from a large genome-wide association study of 173,480 individuals, while data for EPs and CPs were obtained from the UK Biobank. All samples were Europeans. Using genetic variants as instrumental variables, our study found that both eosinophil count (OR 0.85, 95% CI 0.79-0.93, P = 1.06 × 10-4) and eosinophil percentage of white cells (OR 0.84, 95% CI 0.77-0.91, P = 2.43 × 10-5) were associated with decreased risk of EPs. The results were robust in sensitivity analyses and no evidences of horizontal pleiotropy were observed. While we found no significant associations between HBC traits and CPs. Our findings suggested eosinophils might play important roles in the pathogenesis of EPs. Besides, out study provided novel insight into detecting uterine polyps biomarkers using genetic epidemiology approaches.

Causal Effects of Genetically Determined Metabolites on Risk of Polycystic Ovary Syndrome: A Mendelian Randomization Study.

Background: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder that is influenced by both genetic and environmental factors. However, the etiology of PCOS remains unclear. Methods: We conducted a two-sample Mendelian randomization (MR) analysis to assess the causal effects of genetically determined metabolites (GDMs) on the risk of PCOS. We used summary level data of a genome-wide association study (GWAS) on 486 metabolites (n = 7,824) as exposure and a PCOS GWAS consisting of 4,138 cases and 20,129 controls as the outcome. Both datasets were obtained from publicly published databases. For each metabolite, a genetic instrumental variable was generated to assess the relationship between the metabolite and PCOS. For MR analysis, we primarily used the standard inverse variance weighted (IVW) method, while three additional methods-the MR-Egger, weighted median, and MR-PRESSO (pleiotropy residual sum and outlier) methods-were performed as sensitivity analyses. Results: Using genetic variants as predictors, we observed a robust relationship between epiandrosterone sulfate (EPIA-S) and PCOS (PIVW = 0.0186, PMR-Egger = 0.0111; PWeighted-median = 0.0154, and PMR-PRESSO = 0.0290). Similarly, 3-dehydrocarnitine, 4-hydroxyhippurate, hexadecanedioate, and ß-hydroxyisovalerate may also have causal effects on PCOS development. Conclusions: We identified metabolites that might have causal effects on PCOS development. Our study emphasizes the role of genetic factors underlying the causal relationships between metabolites and PCOS and provides novel insights through the integration of metabolomics and genomics to better understand the mechanisms involved in human disease pathogenesis.

Targeted hepatitis E vaccination for women of childbearing age is cost-effective in China.

BACKGROUND: Hepatitis E virus (HEV) infection is hyper-endemic in China, it is characterized with a high morbidity of fulminant hepatitis and mortality in pregnant women. The first hepatitis E vaccine, HEV 239, was licensed in China in 2011 which provides an effective preventive measure. OBJECTIVE: To evaluate the cost-effectiveness of vaccination with HEV 239 in women of childbearing age in China and whether HEV antibody screening should be considered before vaccination. METHODS: A decision tree-Markov model was constructed to simulate HEV infection in a closed female cohort with an average first-marriage age of 25 years and evaluate health and economic outcomes of two potential vaccination strategies, direct vaccination and combined screening and vaccination, from a societal perspective. An incremental cost-effectiveness ratio (ICER, additional costs per disability-adjusted life-year (DALY) averted) was calculated for each vaccination strategy versus no vaccination and between two vaccination strategies. Univariate and probabilistic sensitivity analyses were conducted to assess the robustness of the model findings. RESULTS: ICERs of direct vaccination and combined screening and vaccination versus no vaccination were $4040 and $3114 per DALY averted, respectively, much lower than 1-time Chinese per-capita GDP ($8127). Direct vaccination would need additional $45,455 for each DALY averted compared with combined screening and vaccination, far more than the 3-time per-capita GDP. Probabilistic sensitivity analyses confirmed our findings that two vaccination strategies would be cost-effective if the willingness-to-pay reached the 1-time per-capita GDP, and that combined screening and vaccination would be more cost-effective than direct vaccination strategy. CONCLUSION: Vaccinating women of childbearing age with HEV 239 would cost less than the 1-time per-capita GDP for each DALY averted in China, and the vaccination with a prior screening would be the optimal option.

Relative Contributions of Different Lifestyle Factors to Health-Related Quality of Life in the Elderly.

Much of the previous literature has studied the relationship between individual lifestyle factors and the health-related quality of life (HRQOL). However, only a few studies combined them to explore their relative importance to the HRQOL in the elderly. This study assesses the HRQOL of the urban, rural, and institutionalized Chinese elderly and explores the relative contributions of different lifestyle factors to their HRQOL. The SF-36v2 Health Survey, the WHOQOL-OLD module, and the socio-demographic and lifestyle questionnaire were utilized in this study. Hierarchical regression was performed in order to analyze the results. The physical and mental component scores of the SF-36v2 survey were 47.05 ± 9.95 and 54.92 ± 9.92, respectively. The total score for the WHOQOL-OLD module was 73.01 ± 11.99, with institutionalized persons reporting lower scores. For the physical component of the elderly participants' HRQOL, the R² value changed the most (0.116) when exercise-and-labor-related factors were added in. For the mental component, sleep-related (0.054), and leisure-time-activity-related factors (0.053) caused the largest change of the R² value. For the elderly-specific HRQOL, measured by the WHOQOL-OLD module, the leisure-time-activity-related factors caused the largest change in the R² value (0.119), followed by exercise-and-labor-related factors (0.078). Heterogeneity was present among the three subgroups. In sum, compared with their community-dwelling counterparts, the HRQOL of institutionalized older people was relatively poor and different lifestyle factors contributed to the HRQOL differently.

Effect of lutein supplementation on visual function in nonproliferative diabetic retinopathy.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether supplementation with lutein improved visual function in patients with nonproliferative diabetic retinopathy (NPDR). METHODS AND STUDY DESIGN: In this randomized, double-blind, placebo-controlled trial, 31 patients with NPDR were assigned randomly to 10 mg/d of lutein or identical placebo for 36 weeks. Visual performance indices, including visual acuity (VA), contrast sensitivity (CS) and glare sensitivity (GS) at four different spatial frequencies, were measured at baseline, week 18 and 36. RESULTS: At 36 weeks, a slight improvement in VA was found in the lutein group. A significant association was observed between the changes in VA and the corresponding baseline values in treatment group (r=-0.53; p=0.04). At 36 weeks, the lutein treatment group increased CS at four spatial frequencies, and the improvement achieved statistical significance at 3 cycles/degree (p=0.02). The changes in CS at 3 cycles/degree for the lutein group was marginally significantly greater than those for the placebo group (p=0.09). There was also a slight increase in GS in the lutein group up to week 36, however, no significant changes were found over time in any cycles/degree. CONCLUSIONS: In patients with NPDR, supplementation with lutein resulted in potential improvements in CS at low spatial frequency. Further studies are required to determine the possibility that such intervention could be used as an adjunct therapy to prevent vision loss in diabetic patients.