Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%–2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 5′ region of Uromodulin (UMOD; rs13333226, combined P value of 3.6×10⁻¹¹). The minor G allele is associated with a lower risk of hypertension (OR [95%CI]: 0.87 [0.84–0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860–0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83–0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83–0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk. Hypertension is the leading contributor to global mortality with a global prevalence of 26.4% in 2000, projected to increase to 29.2% by 2025. While 50%–60% of population variation in blood pressure can be attributable to additive genetic factors, all the genetic variants robustly identified so far explain only 1%–2% of the population variance indicating the presence of additional undiscovered risk variants. Using an extreme case-control strategy, we have discovered a SNP in the promoter region of the uromodulin gene (UMOD) to be associated with hypertension (minor allele protective against hypertension). We then validated this association using large-scale population and case-control studies, where similar extreme criteria for selection of cases and controls have been used (21,466 cases and 18,240 controls). As the locus was related to uromodulin, a protein exclusively expressed in the kidneys, we show that the association is independent of renal dysfunction. We also show preliminary evidence that the SNP allele which is protective against hypertension is also protective against cardiovascular events in 26,654 Swedish subjects followed-up for 12 years. The newly discovered UMOD locus for hypertension has the potential to give unique insights into the role of uromodulin in BP regulation and to identify novel drugable targets.

Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r²=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations. Bill & Melinda Gates Foundation.

Background: Attention-Deficit/ Hyperactivity Disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Symptoms related to this disorder cause a significant impairment in school tasks and in the activities of children’s daily lives; an early diagnosis and appropriate treatment could almost certainly help improve their outcomes. The current study, part of the Models Of Child Health Appraised (MOCHA) project, aims to explore the age at which children experience the onset or diagnosis of ADHD in European countries. Methods: A systematic review was done examining the studies reporting the age of onset/diagnosis (AO/AD) of ADHD in European countries (28 European Member States plus 2 European Economic Area countries), published between January 1, 2010 and December 31, 2019. Of the 2276 identified studies, 44 met all the predefined criteria and were included in the review. Results: The lowest mean AO in the children diagnosed with ADHD alone was 2.25 years and the highest was 7.5 years. It was 15.3 years in the children with ADHD and disruptive behaviour disorder. The mean AD ranges between 6.2 and 18.1 years. Conclusions: Our findings indicate that there is a wide variability in both the AO and AD of ADHD, and a too large distance between AO and AD. Since studies in the literature suggest that an early identification of ADHD symptoms may facilitate early referral and treatment, it would be important to understand the underlying reasons behind the wide variability found. Trial registration: PROSPERO registration: CRD42017070631.

To comprehensively identify the determinants of quality of life (QoL) in a population study sample of persons aged 18–50 and 50+. In this observational, cross-sectional study, QoL was measured with the WHOQOL-AGE, a brief instrument designed to measure QoL in older adults. Eight hierarchical regression models were performed to identify determinants of QoL. Variables were entered in the following order: Sociodemographic; Health Habits; Chronic Conditions; Health State description; Vision and Hearing; Social Networks; Built Environment. In the final model, significant variables were retained. The final model was re-run using data from the three countries separately. Complete data were available for 5639 participants, mean age 46.3 (SD 18.4). The final model accounted for 45% of QoL variation and the most relevant contribution was given by sociodemographic data (particularly age, education level and living in Finland: 17.9% explained QoL variation), chronic conditions (particularly depression: 4.6%) and a wide and rich social network (4.6%). Other determinants were presence of disabling pain, learning difficulties and visual problems, and living in usable house that is perceived as non-risky. Some variables were specifically associated to QoL in single countries: age in Poland, alcohol consumption in Spain, angina in Finland, depression in Spain, and self-reported sadness both in Finland and Poland, but not in Spain. Other were commonly associated to QoL: smoking status, bodily aches, being emotionally affected by health problems, good social network and home characteristics. Our results highlight the importance of modifiable determinants of QoL, and provide public health indications that could support concrete actions at country level. In particular, smoking cessation, increasing the level of physical activity, improving social network ties and applying universal design approach to houses and environmental infrastructures could potentially increase QoL of ageing population.

Using data on women aged 50 and over from the WHO’s Survey of Ageing and Adult Health for China, Ghana, India, the Russian Federation and South Africa (N = 17,009), we assess associations between widowhood and socio-economic, health and quality of life deprivations. We find variations in the prevalence and timing of widowhood across the study countries, and associations between widowhood and being in the poorest wealth quintile for all five countries. For other deprivations, national experiences varied, with stronger and more consistent effects for India and China. These findings challenge generalised claims about widowhood and call for more contextualised analysis.