Multi-ancestry polygenic risk scores for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium genome-wide association studies meta-analyses of European- (71 771 cases and 1 059 740 controls) and African-ancestry samples (7482 cases and 129 975 controls). We used LDpred2 and PRS-CSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6781 cases and 103 016 controls) and African-ancestry sample (1385 cases and 12 569 controls). Multi-ancestry PRSs with weights tuned in European-ancestry samples slightly outperformed ancestry-specific PRSs in European-ancestry test samples (e.g. the area under the receiver operating curve [AUC] was 0.609 for PRS-CSx_combinedEUR and 0.608 for PRS-CSxEUR [P = 0.00029]). Multi-ancestry PRSs with weights tuned in African-ancestry samples also outperformed ancestry-specific PRSs in African-ancestry test samples (PRS-CSxAFR: AUC = 0.58, PRS-CSx_combined AFR: AUC = 0.59), although this difference was not statistically significant (P = 0.34). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS might be used to improve performance across diverse populations to identify individuals at highest risk for VTE.

The relationship between serum manganese concentration with all-cause and cause-specific mortality: a retrospective and population-based cross-sectional study.

BACKGROUND: The study aimed to explore the association between manganese concentration and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality in the general population of the United States. METHODS: We integrated the data from the National Health and Nutrition Examination Survey from 2011 to 2018. A total of 9,207 subjects were selected based on the inclusion and exclusion criteria. The relationship between manganese concentration and all-cause, CVD-related, and cancer-related mortality was analyzed by constructing a Cox proportional hazard regression model and a restricted cubic spline (RCS) plot. Additionally, subgroup analyses stratified by age, sex, race/ethnicity, hypertension, diabetes mellitus (DM), chronic heart disease, chronic heart failure, angina pectoris, heart attack, stroke, and BMI were further performed. RESULTS: In the full adjusted model, compared with the lowest quartile, the adjusted hazard ratios with 95% confidence intervals (CIs) for all-cause, CVD-related, and cancer-related mortality across manganese quartiles were (1.11 (0.87,1.41), 0.96 (0.74, 1.23), and 1.23 (0.96, 1.59); P-value for trend =0.041), (0.86 (0.54, 1.37), 0.87 (0.55, 1.40), and 1.07 (0.67, 1.72); P-value for trend =0.906), and (1.45 (0.92, 2.29), 1.14 (0.70, 1.88), and 1.26 (0.75, 2.11); P-value for trend =0.526), respectively. The RCS curve shown a U-shaped association between manganese concentration and all-cause mortality and CVD-related mortality (P-value for nonlinear <0.05). However, there was an increase and then a decrease in the link between manganese concentration and cancer-related mortality (P-value for nonlinear <0.05). Manganese exposure was positively correlated with sex (correlation coefficient, r =0.19, P-value <0.001) and negatively correlated with age (correlation coefficient, r =-0.11, P-value <0.001) and serum creatinine (correlation coefficient, r =-0.12, P-value <0.001), respectively. CONCLUSIONS: Our findings suggest that elevated serum manganese concentrations are associated with all-cause and CVD-related mortality in the U.S. population and that maintenance of serum manganese between 8.67-9.23 µg/L may promote public health.

Multi-ancestry polygenic risk scores for venous thromboembolism.

Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality, with large disparities in incidence rates between Black and White Americans. Polygenic risk scores (PRSs) limited to variants discovered in genome-wide association studies in European-ancestry samples can identify European-ancestry individuals at high risk of VTE. However, there is limited evidence on whether high-dimensional PRS constructed using more sophisticated methods and more diverse training data can enhance the predictive ability and their utility across diverse populations. We developed PRSs for VTE using summary statistics from the International Network against Venous Thrombosis (INVENT) consortium GWAS meta-analyses of European- (71,771 cases and 1,059,740 controls) and African-ancestry samples (7,482 cases and 129,975 controls). We used LDpred2 and PRSCSx to construct ancestry-specific and multi-ancestry PRSs and evaluated their performance in an independent European- (6,261 cases and 88,238 controls) and African-ancestry sample (1,385 cases and 12,569 controls). Multi-ancestry PRSs with weights tuned in European- and African-ancestry samples, respectively, outperformed ancestry-specific PRSs in European- (PRSCSXEUR: AUC=0.61 (0.60, 0.61), PRSCSX_combinedEUR: AUC=0.61 (0.60, 0.62)) and African-ancestry test samples (PRSCSXAFR: AUC=0.58 (0.57, 0.6), PRSCSX_combined AFR: AUC=0.59 (0.57, 0.60)). The highest fifth percentile of the best-performing PRS was associated with 1.9-fold and 1.68-fold increased risk for VTE among European- and African-ancestry subjects, respectively, relative to those in the middle stratum. These findings suggest that the multi-ancestry PRS may be used to identify individuals at highest risk for VTE and provide guidance for the most effective treatment strategy across diverse populations.

A Kano model-based demand analysis and perceived barriers of pulmonary rehabilitation interventions for patients with chronic obstructive pulmonary disease in China.

BACKGROUND: Pulmonary rehabilitation (PR) has been recognized to be an effective therapy for chronic obstructive pulmonary disease (COPD). However, in China, the application of PR interventions is still less promoted. Therefore, this cross-sectional study aimed to understand COPD patients' intention to receive PR, capture the potential personal, social and environmental barriers preventing their willingness of receiving PR, and eventually identify demanding PR services with the highest priority from patients' point of view. METHODS: In total 237 COPD patients were recruited from 8 health care facilities in Zhejiang, China. A self-designed questionnaire was applied to investigate patients' intention to participate in PR and potentially associated factors, including personal dimension such as personal awareness, demographic factors, COPD status and health-related literacy/behaviors, as well as social policies and perceived environmental barriers. The demand questionnaire of PR interventions based on the Kano model was further adopted. RESULTS: Among the 237 COPD patients, 75.1% of COPD patients were willing to participate in PR interventions, while only 62.9% of the investigated patients had heard of PR interventions. Over 90% of patients believed that the cost of PR services and the ratio of medical insurance reimbursement were potential obstacles hindering them from accepting PR services. The multiple linear regression analysis indicated that the PR skills of medical staff, knowledge promotion and public education levels of PR in the community, patients' transportation concerns and degree of support from family and friends were significantly associated with willingness of participation in PR interventions. By using the Kano model, the top 9 most-requisite PR services (i.e., one-dimensional qualities) were identified from patients' point of view, which are mainly diet guidance, education interventions, psychological interventions and lower limb exercise interventions. Subgroup analysis also revealed that patients' demographics, such as breathlessness level, age, education and income levels, could influence their choice of priorities for PR services, especially services related to exercise interventions, respiratory muscle training, oxygen therapy and expectoration. CONCLUSIONS: This study suggested that PR-related knowledge education among patients and their family, as well as providing basic package of PR services with the most-requisite PR items to COPD patients, were considerable approaches to promote PR attendance in the future.