Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Dust diseases in modern Australia : a discussion of the new TSANZ position statement on respiratory surveillance

New measures are designed to improve health outcomes for workers in the coal mining, artificial stone and other dust-generating industrie

Detecting sleep apnoea syndrome in primary care with screening questionnaires and the Epworth sleepiness scale

OBJECTIVE: To examine the utility of apnoea screening questionnaires, alone and in combination with the Epworth sleepiness scale (ESS), for detecting obstructive sleep apnoea (OSA) in primary care. DESIGN, SETTING: Prospective validation study in an Australian general population cohort. PARTICIPANTS: 424 of 772 randomly invited Tasmanian Longitudinal Health Study, 6th decade follow-up participants with OSA symptoms (mean age, 52.9 years; SD, 0.9 year) who completed OSA screening questionnaires and underwent type 4 sleep studies. MAIN OUTCOME MEASURES: Clinically relevant OSA, defined as moderate to severe OSA (15 or more oxygen desaturation events/hour), or mild OSA (5-14 events/hour) and excessive daytime sleepiness (ESS ≥ 8); diagnostic test properties of the Berlin (BQ), STOP-Bang and OSA-50 questionnaires, alone or combined with an ESS ≥ 8. RESULTS: STOP-Bang and OSA-50 correctly identified most participants with clinically relevant OSA (sensitivity, 81% and 86% respectively), but with poor specificity (36% and 21% respectively); the specificity (59%) and sensitivity of the BQ (65%) were both low. When combined with the criterion ESS ≥ 8, the specificity of each questionnaire was high (94-96%), but sensitivity was low (36-51%). Sensitivity and specificity could be adjusted according to specific needs by varying the STOP-Bang cut-off score when combined with the ESS ≥ 8 criterion. CONCLUSIONS: For people likely to trigger OSA assessment in primary care, the STOP-Bang, BQ, and OSA-50 questionnaires, combined with the ESS, can be used to rule in, but not to rule out clinically relevant OSA. Combined use of the STOP-Bang with different cut-off scores and the ESS facilitates a flexible balance between sensitivity and specificity

Sleep apnoea in Australian men: disease burden, co-morbidities, and correlates from the Australian longitudinal study on male health

Abstract Background Obstructive sleep apnoea is a common disorder with under-rated clinical impact, which is increasingly being recognised as having a major bearing on global disease burden. Men are especially vulnerable and become a priority group for preventative interventions. However, there is limited information on prevalence of the condition in Australia, its co-morbidities, and potential risk factors. Methods We used data from 13,423 adult men included in the baseline wave of Ten to Men, an Australian national study of the health of males, assembled using stratified cluster sampling with oversampling from rural and regional areas. Those aged 18–55 years self-completed a paper-based questionnaire that included a question regarding health professional-diagnosed sleep apnoea, physical and mental health status, and health-related behaviours. Sampling weights were used to account for the sampling design when reporting the prevalence estimates. Odds ratios were used to describe the association between health professional-diagnosed sleep apnoea and potential correlates while adjusting for age, country of birth, and body-mass index (BMI). Results Prevalence of self-reported health professional-diagnosed sleep apnoea increased from 2.2 % in age 18–25 years to 7.8 % in the age 45–55 years. Compared with those without sleep apnoea, those with sleep apnoea had significantly poorer physical, mental, and self-rated health as well as lower subjective wellbeing and poorer concentration/remembering (p < 0.001 for all). Sleep apnoea was significantly associated with older age (p < 0.001), unemployment (p < 0.001), asthma (p = 0.011), chronic obstructive pulmonary disease/chronic bronchitis (p = 0.002), diabetes (p < 0.001), hypercholesterolemia (p < 0.001), hypertension (p < 0.001), heart attack (p < 0.001), heart failure (p < 0.001), angina (p < 0.001), depression (p < 0.001), post-traumatic stress disorder (p < 0.001), other anxiety disorders (p < 0.001), schizophrenia (p = 0.002), overweight/obesity (p < 0.001), insufficient physical activity (p = 0.006), smoking (p = 0.005), and high alcohol consumption (p < 0.001). Conclusion Health professional-diagnosed sleep apnoea is relatively common, particularly in older males. Associations between sleep apnoea and cardiovascular, metabolic, respiratory, and psychiatric disorders have important clinical and public health implications. As men are especially vulnerable to sleep apnoea as well as some of its chronic co-morbidities, they are potentially a priority group for health interventions. Modifiable lifestyle related factors such as smoking, alcohol consumption, level of physical activity and BMI are possible key foci for interventions