Measurement invariance testing of the patient health questionnaire-9 (PHQ-9) across people with and without diabetes mellitus from the NHANES, EHMS and UK Biobank datasets

Background: The prevalence of depression is higher among those with diabetes than in the general population. The Patient Health Questionnaire (PHQ-9) is commonly used to assess depression in people with diabetes, but measurement invariance of the PHQ-9 across groups of people with and without diabetes has not yet been investigated. Methods: Data from three independent cohorts from the USA (n=1,886 with diabetes, n=4,153 without diabetes), Quebec, Canada (n= 800 with diabetes, n= 2,411 without diabetes), and the UK (n=4,981 with diabetes, n=145,570 without diabetes), were used to examine measurement invariance between adults with and without diabetes. A series of multiple group confirmatory factor analyses were performed, with increasingly stringent model constraints applied to assess configural, equal thresholds, and equal thresholds and loadings invariance, respectively. One-factor and two-factor (somatic and cognitive-affective items) models were examined. Results: Results demonstrated that the most stringent models, testing equal loadings and thresholds, had satisfactory model fit in the three cohorts for one-factor models (RMSEA = .063 or below and CFI = .978 or above) and two-factor models (RMSEA = .042 or below and CFI = .989 or above). Limitations: Data were from Western countries only and we could not distinguish between type of diabetes. Conclusions: Results provide support for measurement invariance between groups of people with and without diabetes, using either a one-factor or a two-factor model. While the two-factor solution has a slightly better fit, the one-factor solution is more parsimonious. Depending on research or clinical needs, both factor structures can be used

Blood DNA methylation profiling identifies cathepsin Z dysregulation in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular remodelling causing premature death from right heart failure. Established DNA variants influence PAH risk, but susceptibility from epigenetic changes is unknown. We addressed this through epigenome-wide association study (EWAS), testing 865,848 CpG sites for association with PAH in 429 individuals with PAH and 1226 controls. Three loci, at Cathepsin Z (CTSZ, cg04917472), Conserved oligomeric Golgi complex 6 (COG6, cg27396197), and Zinc Finger Protein 678 (ZNF678, cg03144189), reached epigenome-wide significance (p < 10−7) and are hypermethylated in PAH, including in individuals with PAH at 1-year follow-up. Of 16 established PAH genes, only cg10976975 in BMP10 shows hypermethylation in PAH. Hypermethylation at CTSZ is associated with decreased blood cathepsin Z mRNA levels. Knockdown of CTSZ expression in human pulmonary artery endothelial cells increases caspase-3/7 activity (p < 10−4). DNA methylation profiles are altered in PAH, exemplified by the pulmonary endothelial function modifier CTSZ, encoding protease cathepsin Z

Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits

Blood DNA methylation profiling identifies cathepsin Z dysregulation in pulmonary arterial hypertension

\ua9 2024, The Author(s).Pulmonary arterial hypertension (PAH) is characterised by pulmonary vascular remodelling causing premature death from right heart failure. Established DNA variants influence PAH risk, but susceptibility from epigenetic changes is unknown. We addressed this through epigenome-wide association study (EWAS), testing 865,848 CpG sites for association with PAH in 429 individuals with PAH and 1226 controls. Three loci, at Cathepsin Z (CTSZ, cg04917472), Conserved oligomeric Golgi complex 6 (COG6, cg27396197), and Zinc Finger Protein 678 (ZNF678, cg03144189), reached epigenome-wide significance (p &lt; 10−7) and are hypermethylated in PAH, including in individuals with PAH at 1-year follow-up. Of 16 established PAH genes, only cg10976975 in BMP10 shows hypermethylation in PAH. Hypermethylation at CTSZ is associated with decreased blood cathepsin Z mRNA levels. Knockdown of CTSZ expression in human pulmonary artery endothelial cells increases caspase-3/7 activity (p &lt; 10−4). DNA methylation profiles are altered in PAH, exemplified by the pulmonary endothelial function modifier CTSZ, encoding protease cathepsin Z

LongITools:dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases

Abstract The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our ”modern” postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases