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| 2. |
- Griswold, Max G., et al.
(author)
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Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2018
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
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Journal article (peer-reviewed)abstract
- Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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| 3. |
- Le Guen, Yann, et al.
(author)
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Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
- 2023
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
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Journal article (peer-reviewed)abstract
- Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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| 4. |
- Wessel, Jennifer, et al.
(author)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Journal article (peer-reviewed)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 5. |
- Bruzelius, Maria, et al.
(author)
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PDGFB, a new candidate plasma biomarker for venous thromboembolism : results from the VEREMA affinity proteomics study
- 2016
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 128:23, s. E59-E66
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Journal article (peer-reviewed)abstract
- There is a clear clinical need for high-specificity plasma biomarkers for predicting risk of venous thromboembolism (VTE), but thus far, such markers have remained elusive. Utilizing affinity reagents from the Human Protein Atlas project and multiplexed immuoassays, we extensively analyzed plasma samples from 2 individual studies to identify candidate protein markers associated with VTE risk. We screened plasma samples from 88 VTE cases and 85 matched controls, collected as part of the Swedish Venous Thromboembolism Biomarker Study, using suspension bead arrays composed of 755 antibodies targeting 408 candidate proteins. We identified significant associations between VTE occurrence and plasma levels of human immunodeficiency virus type I enhancer binding protein 1 (HIVEP1), von Willebrand factor (VWF), glutathione peroxidase 3 (GPX3), and platelet-derived growth factor beta (PDGFB). For replication, we profiled plasma samples of 580 cases and 589 controls from the French FARIVE study. These results confirmed the association of VWF and PDGFB with VTE after correction for multiple testing, whereas only weak trends were observed for HIVEP1 and GPX3. Although plasma levels of VWF and PDGFB correlated modestly (rho similar to 0.30) with each other, they were independently associated with VTE risk in a joint model in FARIVE (VWF P < .001; PDGFB P = .002). PDGF. was verified as the target of the capture antibody by immunocapture mass spectrometry and sandwich enzyme-linked immunosorbent assay. In conclusion, we demonstrate that high-throughput affinity plasma proteomic profiling is a valuable research strategy to identify potential candidate biomarkers for thrombosis-related disorders, and our study suggests a novel association of PDGFB plasma levels with VTE.
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| 6. |
- Rojo-Perez, Fermina, et al.
(author)
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Active ageing profiles among older adults in Spain : A Multivariate analysis based on SHARE study
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:8
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Journal article (peer-reviewed)abstract
- BackgroundFollowing the active ageing model based on the Health, Lifelong Learning, Participation and Security pillars, this research has a twofold objective: i) to classify older adults according to active ageing profiles, taking into account the four pillars, and ii) to ascertain the relationship between the profiles and personal and contextual factors, as well as well-being and quality of life in old age.MethodsA study sample of 5,566 Spanish older adults who participated in wave 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE) was included. Data were analysed in different steps applying several statistical analyses (Principal Component, Cluster, Discriminant, Multiple Correspondence and bivariate analysis with Pearson chi-square and ANOVA).ResultsFive older adult profiles were obtained (I: with moderate activity; II: quasi-dependents; III: with active ageing-limiting conditions; IV: with diverse and balanced activity; V: with excellent active ageing conditions). The first three profiles were characterised by subjects with a high average age, low educational level, who were retired or housewives, and who perceived a moderate level of loneliness, satisfaction with the social network and quality of life, as well as having a larger family network, but living in small households or alone. In contrast, the latter two profiles showed better personal and contextual conditions, well-being and quality of life.Discussion and conclusionsThe multidimensional approach to active ageing followed in this article has revealed the presence of several older adult profiles, which are confined to groups with better or worse active ageing conditions. In this context, if ageing is a process that reflects the previous way of life, intervention priorities will have to consider actions that promote better conditions during the life cycle.
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| 7. |
- Wu, Yu-Tzu, et al.
(author)
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Education and wealth inequalities in healthy ageing in eight harmonised cohorts in the ATHLOS consortium : a population-based study
- 2020
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In: The Lancet Public Health. - 2468-2667. ; 5:7, s. e386-e394
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Journal article (peer-reviewed)abstract
- BACKGROUND: The rapid growth of the size of the older population is having a substantial effect on health and social care services in many societies across the world. Maintaining health and functioning in older age is a key public health issue but few studies have examined factors associated with inequalities in trajectories of health and functioning across countries. The aim of this study was to investigate trajectories of healthy ageing in older men and women (aged ≥45 years) and the effect of education and wealth on these trajectories.METHODS: This population-based study is based on eight longitudinal cohorts from Australia, the USA, Japan, South Korea, Mexico, and Europe harmonised by the EU Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. We selected these studies from the repository of 17 ageing studies in the ATHLOS consortium because they reported at least three waves of collected data. We used multilevel modelling to investigate the effect of education and wealth on trajectories of healthy ageing scores, which incorporated 41 items of physical and cognitive functioning with a range between 0 (poor) and 100 (good), after adjustment for age, sex, and cohort study.FINDINGS: We used data from 141 214 participants, with a mean age of 62·9 years (SD 10·1) and an age range of 45-106 years, of whom 76 484 (54·2%) were women. The earliest year of baseline data was 1992 and the most recent last follow-up year was 2015. Education and wealth affected baseline scores of healthy ageing but had little effect on the rate of decrease in healthy ageing score thereafter. Compared with those with primary education or less, participants with tertiary education had higher baseline scores (adjusted difference in score of 10·54 points, 95% CI 10·31-10·77). The adjusted difference in healthy ageing score between lowest and highest quintiles of wealth was 8·98 points (95% CI 8·74-9·22). Among the eight cohorts, the strongest inequality gradient for both education and wealth was found in the Health Retirement Study from the USA.INTERPRETATION: The apparent difference in baseline healthy ageing scores between those with high versus low education levels and wealth suggests that cumulative disadvantage due to low education and wealth might have largely deteriorated health conditions in early life stages, leading to persistent differences throughout older age, but no further increase in ageing disparity after age 70 years. Future research should adopt a lifecourse approach to investigate mechanisms of health inequalities across education and wealth in different societies.FUNDING: European Union Horizon 2020 Research and Innovation Programme.
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| 8. |
- Barmpas, Petros, et al.
(author)
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A divisive hierarchical clustering methodology for enhancing the ensemble prediction power in large scale population studies : the ATHLOS project
- 2022
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In: Health Information Science and Systems. - : Springer Science and Business Media LLC. - 2047-2501. ; 10:1
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Journal article (peer-reviewed)abstract
- The ATHLOS cohort is composed of several harmonized datasets of international groups related to health and aging. As a result, the Healthy Aging index has been constructed based on a selection of variables from 16 individual studies. In this paper, we consider additional variables found in ATHLOS and investigate their utilization for predicting the Healthy Aging index. For this purpose, motivated by the volume and diversity of the dataset, we focus our attention upon data clustering, where unsupervised learning is utilized to enhance prediction power. Thus we show the predictive utility of exploiting hidden data structures. In addition, we demonstrate that imposed computation bottlenecks can be surpassed when using appropriate hierarchical clustering, within a clustering for ensemble classification scheme, while retaining prediction benefits. We propose a complete methodology that is evaluated against baseline methods and the original concept. The results are very encouraging suggesting further developments in this direction along with applications in tasks with similar characteristics. A straightforward open source implementation for the R project is also provided (https://github.com/Petros-Barmpas/HCEP).
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| 9. |
- Guido, Davide, et al.
(author)
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Pain rates in general population for the period 1991-2015 and 10-years prediction : results from a multi-continent age-period-cohort analysis
- 2020
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In: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 21:1
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Journal article (peer-reviewed)abstract
- Background Pain is a common symptom, often associated with neurological and musculoskeletal conditions, and experienced especially by females and by older people. The aims of this study are to evaluate the temporal variations of pain rates among general populations for the period 1991-2015 and to project 10-year pain rates. Methods We used the harmonized dataset of ATHLOS project, which included 660,028 valid observations in the period 1990-2015 and we applied Bayesian age-period-cohort modeling to perform projections up to 2025. The harmonized Pain variable covers the content self-reported pain experienced at the time of the interview, with a dichotomous (yes or no) modality. Results Pain rates were higher among females, older subjects, in recent periods, and among observations referred to cohorts of subjects born between the 20s and the 60s. The 10-year projections indicate a noteworthy increase in pain rates in both genders and particularly among subjects aged 66 or over, for whom a 10-20% increase in pain rate is foreseen; among females only, a 10-15% increase in pain rates is foreseen for those aged 36-50. Conclusions Projected increase in pain rates will require specific interventions by health and welfare systems, as pain is responsible for limited quality of subjective well-being, reduced employment rates and hampered work performance. Worksite and lifestyle interventions will therefore be needed to limit the impact of projected higher pain rates.
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| 10. |
- Sanchez-Niubo, Albert, et al.
(author)
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Development of a common scale for measuring healthy ageing across the world : results from the ATHLOS consortium
- 2021
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 50:3, s. 880-892
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Journal article (peer-reviewed)abstract
- BACKGROUND: Research efforts to measure the concept of healthy ageing have been diverse and limited to specific populations. This diversity limits the potential to compare healthy ageing across countries and/or populations. In this study, we developed a novel measurement scale of healthy ageing using worldwide cohorts.METHODS: In the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) project, data from 16 international cohorts were harmonized. Using ATHLOS data, an item response theory (IRT) model was used to develop a scale with 41 items related to health and functioning. Measurement heterogeneity due to intra-dataset specificities was detected, applying differential item functioning via a logistic regression framework. The model accounted for specificities in model parameters by introducing cohort-specific parameters that rescaled scores to the main scale, using an equating procedure. Final scores were estimated for all individuals and converted to T-scores with a mean of 50 and a standard deviation of 10.RESULTS: A common scale was created for 343 915 individuals above 18 years of age from 16 studies. The scale showed solid evidence of concurrent validity regarding various sociodemographic, life and health factors, and convergent validity with healthy life expectancy (r = 0.81) and gross domestic product (r = 0.58). Survival curves showed that the scale could also be predictive of mortality.CONCLUSIONS: The ATHLOS scale, due to its reliability and global representativeness, has the potential to contribute to worldwide research on healthy ageing.
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