Cuicui Wang

Depression represents a significant global public health challenge, and marital status has been recognized as a potential risk factor. However, previous investigations of this association have primarily focused on Western samples with substantial heterogeneity. Our study aimed to examine the association between marital status and depressive symptoms across countries with diverse cultural backgrounds using a large-scale, two-stage, cross-country analysis. We used nationally representative, de-identified individual-level data from seven countries, including the USA, the UK, Mexico, Ireland, Korea, China and Indonesia (106,556 cross-sectional and 20,865 longitudinal participants), representing approximately 541 million adults. The follow-up duration ranged from 4 to 18 years. Our analysis revealed that unmarried individuals had a higher risk of depressive symptoms than their married counterparts across all countries (pooled odds ratio, 1.86; 95% confidence interval (CI), 1.61–2.14). However, the magnitude of this risk was influenced by country, sex and education level, with greater risk in Western versus Eastern countries (β = 0.36; 95% CI, 0.16–0.56; P < 0.001), among males versus females (β = 0.25; 95% CI, 0.003–0.47; P = 0.047) and among those with higher versus lower educational attainment (β₂ = 0.34; 95% CI, 0.11–0.56; P = 0.003). Furthermore, alcohol drinking causally mediated increased later depressive symptom risk among widowed, divorced/separated and single Chinese, Korean and Mexican participants (all P < 0.001). Similarly, smoking was as identified as a causal mediator among single individuals in China and Mexico, and the results remained unchanged in the bootstrap resampling validation and the sensitivity analyses. Our cross-country analysis suggests that unmarried individuals may be at greater risk of depression, and any efforts to mitigate this risk should consider the roles of cultural context, sex, educational attainment and substance use.

Background: Epigenome-wide association studies of ambient fine particulate matter (PM_2.5) have been reported. However, few have examined PM_2.5 components (PMCs) and sources or included repeated measures. The lack of high-resolution exposure measurements is the key limitation. We hypothesized that significant changes in DNA methylation might vary by PMCs and the sources. Methods: We predicted the annual average of 14 PMCs using novel high-resolution exposure models across the contiguous U.S., between 2000–2018. The resolution was 50 m × 50 m in the Greater Boston Area. We also identified PM_2.5 sources using positive matrix factorization. We repeatedly collected blood samples and measured leukocyte DNAm with the Illumina HumanMethylation450K BeadChip in the Normative Aging Study. We then used median regression with subject-specific intercepts to estimate the associations between long-term (one-year) exposure to PMCs / PM_2.5 sources and DNA methylation at individual cytosine-phosphate-guanine CpG sites. Significant probes were identified by the number of independent degrees of freedom approach, using the number of principal components explaining > 95% of the variation of the DNA methylation data. We also performed regional and pathway analyses to identify significant regions and pathways. Results: We included 669 men with 1,178 visits between 2000–2013. The subjects had a mean age of 75 years. The identified probes, regions, and pathways varied by PMCs and their sources. For example, iron was associated with 6 probes and 6 regions, whereas nitrate was associated with 15 probes and 3 regions. The identified pathways from biomass burning, coal burning, and heavy fuel oil combustion sources were associated with cancer, inflammation, and cardiovascular diseases, whereas there were no pathways associated with all traffic. Conclusions: Our findings showed that the effects of PM_2.5 on DNAm varied by its PMCs and sources.

Objective: Higher optimism is associated with reduced mortality and a lower risk of age-related chronic diseases. DNA methylation (DNAm) may provide insight into mechanisms underlying these relationships. We hypothesized that DNAm would differ among older individuals who are more versus less optimistic. Methods: Using cross-sectional data from two population-based cohorts of women with diverse races/ethnicities (n = 3816) and men (only White, n = 667), we investigated the associations of optimism with epigenome-wide leukocyte DNAm. Random-effects meta-analyses were subsequently used to pool the individual results. Significantly differentially methylated cytosine-phosphate-guanines (CpGs) were identified by the “number of independent degrees of freedom” approach: effective degrees of freedom correction using the number of principal components (PCs), explaining >95% of the variation of the DNAm data (PC-correction). We performed regional analyses using comb-p and pathway analyses using the Ingenuity Pathway Analysis software. Results: We found that essentially all CpGs (total probe N = 359,862) were homogeneous across sex and race/ethnicity in the DNAm-optimism association. In the single CpG site analyses based on homogeneous CpGs, we identified 13 significantly differentially methylated probes using PC-correction. We found four significantly differentially methylated regions and two significantly differentially methylated pathways. The annotated genes from the single CpG site and regional analyses are involved in psychiatric disorders, cardiovascular disease, cognitive impairment, and cancer. Identified pathways were related to cancer, and neurodevelopmental and neurodegenerative disorders. Conclusion: Our findings provide new insights into possible mechanisms underlying optimism and health.

Background: Comorbidities, any other coexisting diseases in patients with a particular index disease, are known to increase the mortality of a stroke. However, the association of pre-existing comorbidities with stroke risk has not been fully studied. Methods: This study included 16,246 adults from a prospective community-based cohort with a baseline survey conducted in 2013 in China. Participants were followed up with hospitalization records and the Cause of Death Registry. The association of eight pre-existing comorbidities (coronary heart disease, hyperlipidemia, hypertension, diabetes, previous stroke, chronic obstructive pulmonary disease, nephropathy, and cancer) with stroke risk was analyzed using the Cox proportional hazard model in 2020. Results: At a median follow-up of 5.5 years, a total of 449 participants (206 men and 243 women) developed a stroke. Four pre-existing comorbidities (hypertension, congenital heart disease, previous stroke, and diabetes) were independently and positively associated with the risk for all types of stroke. The adjusted hazard ratios for participants with only 1 and ≥ 2 pre-existing comorbidities compared with those without pre-existing conditions were 1.96 (95% CI: 1.44, 2.67; P < 0.001) and 2.87 (95% CI; 2.09, 3.94; P < 0.001) for total stroke, respectively. Moreover, male and female participants with a combination of increased age and a higher number of pre-existing comorbidities experienced the greatest risk of stroke. Conclusions: The number of pre-existing comorbidities was independently associated with an increased risk of stroke. There was a synergic effect between increased age and a higher number of pre-existing comorbidities on stroke occurrence. Our novel findings emphasize the importance and potential application of pre-existing comorbidities as a risk indicator in stroke prevention.

Objectives Diabetes mellitus has been associated with stroke. However, the association between fasting blood glucose (FBG) and stroke risk in a general population remains not clear. The purpose of our study was to examine the FBG levels on subsequent stroke risk in a community-based cohort in China. Design Prospective cohort study, employing Cox proportional hazard model to analyse the association of FBG levels with stroke risk. Setting A community-based cohort study included adults participating in a baseline survey conducted in 2013 in Changshu, eastern China. Participants 16 113 participants were recruited with a multistage sampling method, excluding participants with severe disability, severe cancer, severe psychiatric disturbance or previous stroke before enrolment. Primary outcome measures Stroke events. Results During a median follow-up of 5.5 years, 417 incident cases of stroke were identified. The adjusted HR for total and ischaemic stroke for participants in the fourth quartile of FBG compared with the first quartile was 1.44 (95% CI 1.07 to 1.94) and 1.57 (95% CI 1.11 to 2.21), respectively. FBG levels of ≥7.0 mmol/L were associated with an increased risk of stroke based on two clinical classifications (American Diabetes Association: 1.68 (1.24 to 2.27); WHO: 1.62 (1.21, 2.13)). In stratified analyses, risk associations existed in women (HR: 1.92, 95% CI 1.22 to 3.01) and postmenopausal women (HR: 1.68, 95% CI 1.06 to 2.68) for the fourth quartile versus the first. More importantly, the meta-analysis observed a positive association between FBG levels and stroke risk (pooled HR: 1.70, 95% CI 1.27 to 2.29; n=7)). Conclusions Higher FBG level was independently associated with an increased risk of stroke in Chinese adults, especially significant in women.