Summary Background Quantification of the disease burden caused by different risks informs prevention by providing an account of health loss different to that provided by a disease-by-disease analysis. No complete revision of global disease burden caused by risk factors has been done since a comparative risk assessment in 2000, and no previous analysis has assessed changes in burden attributable to risk factors over time. Methods We estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010. We estimated exposure distributions for each year, region, sex, and age group, and relative risks per unit of exposure by systematically reviewing and synthesising published and unpublished data. We used these estimates, together with estimates of cause-specific deaths and DALYs from the Global Burden of Disease Study 2010, to calculate the burden attributable to each risk factor exposure compared with the theoretical-minimum-risk exposure. We incorporated uncertainty in disease burden, relative risks, and exposures into our estimates of attributable burden. Findings In 2010, the three leading risk factors for global disease burden were high blood pressure (7·0% [95% uncertainty interval 6·2–7·7] of global DALYs), tobacco smoking including second-hand smoke (6·3% [5·5–7·0]), and alcohol use (5·5% [5·0–5·9]). In 1990, the leading risks were childhood underweight (7·9% [6·8–9·4]), household air pollution from solid fuels (HAP; 7·0% [5·6–8·3]), and tobacco smoking including second-hand smoke (6·1% [5·4–6·8]). Dietary risk factors and physical inactivity collectively accounted for 10·0% (95% UI 9·2–10·8) of global DALYs in 2010, with the most prominent dietary risks being diets low in fruits and those high in sodium. Several risks that primarily affect childhood communicable diseases, including unimproved water and sanitation and childhood micronutrient deficiencies, fell in rank between 1990 and 2010, with unimproved water we and sanitation accounting for 0·9% (0·4–1·6) of global DALYs in 2010. However, in most of sub-Saharan Africa childhood underweight, HAP, and non-exclusive and discontinued breastfeeding were the leading risks in 2010, while HAP was the leading risk in south Asia. The leading risk factor in Eastern Europe, most of Latin America, and southern sub-Saharan Africa in 2010 was alcohol use; in most of Asia, North Africa and Middle East, and central Europe it was high blood pressure. Despite declines, tobacco smoking including second-hand smoke remained the leading risk in high-income north America and western Europe. High body-mass index has increased globally and it is the leading risk in Australasia and southern Latin America, and also ranks high in other high-income regions, North Africa and Middle East, and Oceania. Interpretation Worldwide, the contribution of different risk factors to disease burden has changed s...

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Behavioral and lifestyle factors have been shown to relate to a number of health-related outcomes, yet there is a need for studies that examine their relationship to molecular aging rates. Toward this end, we use recent epigenetic biomarkers of age that have previously been shown to predict all-cause mortality, chronic conditions and age-related functional decline. We analyze cross-sectional data from 4,173 postmenopausal female participants from the Women's Health Initiative, as well as 402 male and female participants from the Italian cohort study, Invecchiare nel Chianti.Extrinsic epigenetic age acceleration (EEAA) exhibits significant associations with fish intake (p=0.02), moderate alcohol consumption (p=0.01), education (p=3×10-5), BMI (p=0.01), and blood carotenoid levels (p=1×10-5)—an indicator of fruit and vegetable consumption, whereas intrinsic epigenetic age acceleration (IEAA) is associated with poultry intake (p=0.03) and BMI (p=0.05). Both EEAA and IEAA were also found to relate to indicators of metabolic syndrome, which appear to mediate their associations with BMI. Metformin—the first-line medication for the treatment of type 2 diabetes—does not delay epigenetic aging in this observational study. Finally, longitudinal data suggests that an increase in BMI is associated with increase in both EEAA and IEAA.Overall, the epigenetic age analysis of blood confirms the conventional wisdom regarding the benefits of eating a high plant diet with lean meats, moderate alcohol consumption, physical activity, and education, as well as the health risks of obesity and metabolic syndrome.

BackgroundEpigenetic biomarkers of aging (the “epigenetic clock”) have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors.ResultsWe analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue.ConclusionsEpigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-016-1030-0) contains supplementary material, which is available to authorized users.

Accumulating evidence suggests that outdoor air pollution may have a significant impact on central nervous system (CNS) health and disease. To address this issue, the National Institute of Environmental Health Sciences/National Institute of Health convened a panel of research scientists that was assigned the task of identifying research gaps and priority goals essential for advancing this growing field and addressing an emerging human health concern. Here, we review recent findings that have established the effects of inhaled air pollutants in the brain, explore the potential mechanisms driving these phenomena, and discuss the recommended research priorities/approaches that were identified by the panel.

Evidence from animal and cell models suggests that pesticides cause a neurodegenerative process leading to Parkinson's disease (PD). Human data are insufficient to support this claim for any specific pesticide, largely because of challenges in exposure assessment. The authors developed and validated an exposure assessment tool based on geographic information systems that integrated information from California Pesticide Use Reports and land-use maps to estimate historical exposure to agricultural pesticides in the residential environment. In 1998-2007, the authors enrolled 368 incident PD cases and 341 population controls from the Central Valley of California in a case-control study. They generated estimates for maneb and paraquat exposures incurred between 1974 and 1999. Exposure to both pesticides within 500 m of the home increased PD risk by 75% (95% confidence interval (CI): 1.13, 2.73). Persons aged < or =60 years at the time of diagnosis were at much higher risk when exposed to either maneb or paraquat alone (odds ratio = 2.27, 95% CI: 0.91, 5.70) or to both pesticides in combination (odds ratio = 4.17, 95% CI: 1.15, 15.16) in 1974-1989. This study provides evidence that exposure to a combination of maneb and paraquat increases PD risk, particularly in younger subjects and/or when exposure occurs at younger ages.

The authors evaluated the effect of air pollution on the occurrence of birth defects ascertained by the California Birth Defects Monitoring Program in neonates and fetuses delivered in southern California in 1987-1993. By using measurements from ambient monitoring stations of carbon monoxide (CO), nitrogen dioxide, ozone, and particulate matter <10 microm in aerodynamic diameter, they calculated average monthly exposure estimates for each pregnancy. Conventional, polytomous, and hierarchical logistic regression was used to estimate odds ratios for subgroups of cardiac and orofacial defects. Odds ratios for cardiac ventricular septal defects increased in a dose-response fashion with increasing second-month CO exposure (odds ratio (OR)(2nd quartile) CO = 1.62, 95% confidence interval (CI): 1.05, 2.48; OR(3rd quartile) CO = 2.09, 95% CI: 1.19, 3.67; OR(4th quartile) CO = 2.95, 95% CI: 1.44, 6.05). Similarly, risks for aortic artery and valve defects, pulmonary artery and valve anomalies, and conotruncal defects increased with second-month ozone exposure. The study was inconclusive for other air pollutants. The authors' results are supported by the specificity of the timing of the effect and some evidence from animal data; however, this is the first known study to link ambient air pollution during a vulnerable window of development to human malformations. Confirmation by further studies is needed.

It has been a long standing hypothesis that blood tissue of PD Parkinson's disease (PD) patients may exhibit signs of accelerated aging. Here we use DNA methylation based biomarkers of aging (“epigenetic clock”) to assess the aging rate of blood in two ethnically distinct case-control data sets. Using n=508 Caucasian and n=84 Hispanic blood samples, we assess a) the intrinsic epigenetic age acceleration of blood (IEAA), which is independent of blood cell counts, and b) the extrinsic epigenetic age acceleration rate of blood (EEAA) which is associated with age dependent changes in blood cell counts. Blood of PD subjects exhibits increased age acceleration according to both IEAA (p=0.019) and EEAA (p=6.1×10−3). We find striking differences in imputed blood cell counts between PD cases and controls. Compared to control subjects, PD subjects contains more granulocytes (p=1.0×10−9 in Caucasians, p=0.00066 in Hispanics) but fewer T helper cells (p=1.4×10−6 in Caucasians, p=0.0024 in Hispanics) and fewer B cells (p=1.6×10−5 in Caucasians, p=4.5×10−5 in Hispanics). Overall, this study shows that the epigenetic age of the immune system is significantly increased in PD patients and that granulocytes play a significant role.