Susceptibility gene identification and risk evaluation model construction by transcriptome-wide association analysis for salt sensitivity of blood pressure.

BACKGROUND: Salt sensitivity of blood pressure (SSBP) is an intermediate phenotype of hypertension and is a predictor of long-term cardiovascular events and death. However, the genetic structures of SSBP are uncertain, and it is difficult to precisely diagnose SSBP in population. So, we aimed to identify genes related to susceptibility to the SSBP, construct a risk evaluation model, and explore the potential functions of these genes. METHODS AND RESULTS: A genome-wide association study of the systemic epidemiology of salt sensitivity (EpiSS) cohort was performed to obtain summary statistics for SSBP. Then, we conducted a transcriptome-wide association study (TWAS) of 12 tissues using FUSION software to predict the genes associated with SSBP and verified the genes with an mRNA microarray. The potential roles of the genes were explored. Risk evaluation models of SSBP were constructed based on the serial P value thresholds of polygenetic risk scores (PRSs), polygenic transcriptome risk scores (PTRSs) and their combinations of the identified genes and genetic variants from the TWAS. The TWAS revealed that 2605 genes were significantly associated with SSBP. Among these genes, 69 were differentially expressed according to the microarray analysis. The functional analysis showed that the genes identified in the TWAS were enriched in metabolic process pathways. The PRSs were correlated with PTRSs in the heart atrial appendage, adrenal gland, EBV-transformed lymphocytes, pituitary, artery coronary, artery tibial and whole blood. Multiple logistic regression models revealed that a PRS of P < 0.05 had the best predictive ability compared with other PRSs and PTRSs. The combinations of PRSs and PTRSs did not significantly increase the prediction accuracy of SSBP in the training and validation datasets. CONCLUSIONS: Several known and novel susceptibility genes for SSBP were identified via multitissue TWAS analysis. The risk evaluation model constructed with the PRS of susceptibility genes showed better diagnostic performance than the transcript levels, which could be applied to screen for SSBP high-risk individuals.

The prevalence of disability and associated factors among community adults in the baseline of CHCN-BTH Cohort Study.

BACKGROUND: Disability was a major public health problem in China. However, the prevalence of disabilities in community-dwelling adults and their relationships to chronic physical conditions were unclear. We aimed to estimate the prevalence of disabilities and associated factors among a large community-based cohort in China. METHODS: Participants who were local permanent residents aged 18 years or above and completed the disability assessments were selected from the Cohort study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) from 2017 to 2019. Disability was assessed using five questions about impairments and activity limitations based on the International Classification of Functioning (ICF), Disability and Health. Univariate, multivariate and multilevel logistic regressions were conducted to estimate the associations between disabilities and associated factors. RESULTS: Totally, 12,871 community-dwelling adults completed the survey. Among of them, 12.9% (95% CI: 12.3%-13.5%) reported having any disability. The prevalence of any disability was significantly higher in participants who were older age, widowed, retired and smokers, had higher BMI, average monthly income < 5000 RMB, lower education level, lower physical exercise frequency and heavy physical labor. Multilevel logistic regressions showed that there were significant associations between disabilities with chronic physical conditions, especially in the vision impairment with lower back pain, and hearing impairment as well as difficulty walking without special equipment with injuries. CONCLUSIONS: Many Chinese adults suffered from disabilities. Sustained efforts should be made to develop specific population-based health promotion and prevention programs for disabilities in China. TRAIL REGISTRATION: ChiCTR1900024725 (25/07/2019).

Associations between depressive, anxiety, stress symptoms and elevated blood pressure: Findings from the CHCN-BTH cohort study and a two-sample Mendelian randomization analysis.

BACKGROUND: We aimed to determine whether depressive, anxiety, stress symptoms were associated with the risk of elevated blood pressure by performing longitudinal cohort and Mendelian Randomization (MR) analyses. METHODS: We used data from the Cohort Study on Chronic Disease of Community Natural Population in the Beijing-Tianjin-Hebei region (CHCN-BTH) from 2017 to 2021. The Depression-Anxiety-Stress Scale was used to evaluate the depressive, anxiety, stress symptoms. The longitudinal associations between depressive, anxiety, stress symptoms and elevated blood pressure were estimated using Cox proportional regression models. Two-sample MR analysis was performed using the Inverse-variance weighted (IVW), weighted median, and MR-Egger to explore the causal relationships between depressive, anxiety, stress symptoms and elevated blood pressure. RESULTS: In total, 5624 participants were included. The risk of SBP ≥ 140 mmHg or DBP ≥ 90 mmHg was significantly higher in participants with baseline anxiety symptoms (HR = 1.48, 95 % CI: 1.03 to 2.12, P = 0.033; HR = 1.56, 95 % CI: 1.05 to 2.32, P = 0.028), especially in men and individuals with higher educational levels, independent of baseline depression and anxiety at the two-year follow-up. The two-sample MR analysis showed positive associations between depressive, anxiety, stress symptoms and elevated blood pressure. LIMITATION: Self-reported mental health symptoms, relatively shorter follow-up duration and the European-derived genome-wide association study data for MR analysis. CONCLUSIONS: Anxiety symptoms were positively associated with elevated blood pressures in the longitudinal analysis independent of depression, stress, and other confounders. The results were verified in MR analysis, providing evidence for causal effects of anxiety symptoms on the risk of elevated blood pressure.