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Gibson R, Eriksen R, Chambers E, et al., 2019, Intakes and food sources of dietary fibre and their associations with measures of body composition and inflammation in UK adults: Cross-sectional analysis of the Airwave Health Monitoring Study, Nutrients, Vol: 11, ISSN: 2072-6643
The purpose of this study was to investigate the associations between intakes of fibre from the main food sources of fibre in the UK diet with body mass index (BMI), percentage body fat (%BF), waist circumference (WC) and C-reactive protein (CRP). Participants enrolled in the Airwave Health Monitoring Study (2007–2012) with 7-day food records (n = 6898; 61% men) were included for cross-sectional analyses. General linear models evaluated associations across fifths of fibre intakes (total, vegetable, fruit, potato, whole grain and non-whole grain cereal) with BMI, %BF, WC and CRP. Fully adjusted analyses showed inverse linear trends across fifths of total fibre and fibre from fruit with all outcome measures (ptrend < 0.0001). Vegetable fibre intake showed an inverse association with WC (ptrend 0.0156) and CRP (ptrend 0.0005). Fibre from whole grain sources showed an inverse association with BMI (ptrend 0.0002), %BF (ptrend 0.0007) and WC (ptrend 0.0004). Non-whole grain cereal fibre showed an inverse association with BMI (Ptrend 0.0095). Direct associations observed between potato fibre intake and measures of body composition and inflammation were attenuated in fully adjusted analyses controlling for fried potato intake. Higher fibre intake has a beneficial association on body composition, however, there are differential associations based on the food source.
Sung YJ, de Las Fuentes L, Winkler TW, et al., 2019, A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure, Human Molecular Genetics, Vol: 28, Pages: 2615-2633, ISSN: 0964-6906
Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
Gill D, Georgakis MK, Koskeridis F, et al., 2019, Use of genetic variants related to antihypertensive drugs to inform on efficacy and side effects, Circulation, Vol: 140, Pages: 270-279, ISSN: 0009-7322
Background: Drug effects can be investigated through natural variation in the genes for their protein targets. The current study aimed to use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs, which are amongst the most commonly used medications worldwide. Methods: Genetic proxies for the effect of antihypertensive drug classes were identified as variants in the genes for the corresponding targets that associated with systolic blood pressure (SBP) at genome-wide significance. Mendelian randomization (MR) estimates for drug effects on coronary heart disease (CHD) and stroke risk were compared to randomized controlled trial (RCT) results. Phenome-wide association study (PheWAS) in the UK Biobank was performed to identify potential side effects and repurposing opportunities, with findings investigated in the Vanderbilt University Biobank (BioVU) and in observational analysis of the UK Biobank.Results: Suitable genetic proxies for angiotensin-converting-enzyme inhibitors (ACEIs), beta-blockers (BBs) and calcium channel blockers (CCBs) were identified. MR estimates for their effect on CHD and stroke risk respectively were comparable to results from RCTs against placebo. PheWAS in the UK Biobank identified an association of the CCB standardized genetic risk score with increased risk of diverticulosis (odds ratio [OR] 1.02 per standard deviation increase, 95%CI 1.01-1.04), with a consistent estimate found in BioVU (OR 1.01, 95%CI 1.00-1.02). Cox regression analysis of drug use in the UK Biobank suggested that this association was specific to non-dihydropyridine CCBs (hazard ratio [HR] 1.49 considering thiazide diuretics as a comparator, 95%CI 1.04-2.14), but not dihydropyridine CCBs (HR 1.04, 95%CI 0.83-1.32). Conclusions: Genetic variants can be used to explore the efficacy and side effects of antihypertensive medications. The identified potential effect of non-dihydropyridine CCBs on diverticulosis risk could have cli
Karimi M, Castagne R, Delpierre C, et al., 2019, Early-life inequalities and biological ageing: A multi-system biological health score approach in the Understanding Society study, Journal of Epidemiology and Community Health, Vol: 73, Pages: 693-702, ISSN: 0143-005X
Social position is known to play a role in the quality of ageing, notably through the stimulation/dysregulation of key physiological systems in response to external stresses. Using data from one wave of the Understanding Society panel study including 9,088 participants, we defined, as an extension of the Allostatic Load, a synthetic biological health score (BHS) capturing the wear-and-tear of four physiological systems (endocrine, inflammatory, cardiovascular, and metabolic systems), and two organs (liver and kidney). We used 16 established blood-derived biomarkers of these systems to calculate the BHS and explored the relative contribution of socio-economic position to the BHS and its main components across age groups.We identified a systematic decreasing education-related gradient of the BHS (p<0.001) leading to lower biological risk in participants with longer education. Education-related differences in the BHS were detected early in life, and were not attributable to lifestyle and behavioural factors. We found a consistent contribution of the inflammatory and metabolic systems to the overall score throughout from early adulthood onwards, while the contribution of the other four systems seem to vary across age groups and gender. Our findings highlight the social-to-biological processes ultimately leading to health inequalities, and suggest that such disparities can already be detected in the 20-40 years old age group and cannot be fully explained by lifestyle and behavioural factors. This may define early adulthood social condition as a precursor to accelerated biological ageing and as an important target for public health policies.
Evangelou E, Warren H, Mosen-Ansorena D, et al., 2019, Large-scale meta-analysis of GWAS in over one million individuals identifies more than 1,000 novel independent variants associated with blood pressure, 51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Publisher: NATURE PUBLISHING GROUP, Pages: 842-843, ISSN: 1018-4813
Malik R, Chauhan G, Traylor M, et al., 2019, Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes (vol 50, pg 524, 2018), Nature Genetics, Vol: 51, Pages: 1192-1193, ISSN: 1061-4036
Turcot V, Lu Y, Highland HM, et al., 2019, Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity, Nature Genetics, Vol: 51, Pages: 1191-1192, ISSN: 1061-4036
In the HTML version of this article initially published, the author groups ‘CHD Exome+ Consortium’, ‘EPIC-CVD Consortium’, ‘ExomeBP Consortium’, ‘Global Lipids Genetic Consortium’, ‘GoT2D Genes Consortium’, ‘EPIC InterAct Consortium’, ‘INTERVAL Study’, ‘ReproGen Consortium’, ‘T2D-Genes Consortium’, ‘The MAGIC Investigators’ and ‘Understanding Society Scientific Group’ appeared at the end of the author list but should have appeared earlier in the list, after author Krina T. Zondervan. The errors have been corrected in the HTML version of the article.
Freni Sterrantino A, Elliott P, Blangiardo M, et al., 2019, Bayesian spatial modelling for quasi-experimental designs: an interrupted time series study of the opening of Municipal Waste Incinerators in relation to infant mortality and sex ratio, Environment International, Vol: 128, Pages: 109-115, ISSN: 0160-4120
BackgroundThere is limited evidence on potential health risks from Municipal Waste Incinerators (MWIs), and previous studies on birth outcomes show inconsistent results. Here, we evaluate whether the opening of MWIs is associated with infant mortality and sex ratio in the surrounding areas, extending the Interrupted Time Series (ITS) methodological approach to account for spatial dependencies at the small area level.MethodsWe specified a Bayesian hierarchical model to investigate the annual risks of infant mortality and sex-ratio (female relative to male) within 10 km of eight MWIs in England and Wales, during the period 1996–2012. We included comparative areas matched one-to-one of similar size and area characteristics.ResultsDuring the study period, infant mortality rates decreased overall by 2.5% per year in England. The opening of an incinerator in the MWI area was associated with −8 deaths per 100,000 infants (95% CI −62, 40) and with a difference in sex ratio of −0.004 (95% CI −0.02, 0.01), comparing the period after opening with that before, corrected for before-after trends in the comparator areas.ConclusionOur method is suitable for the analysis of quasi-experimental time series studies in the presence of spatial structure and when there are global time trends in the outcome variable. Based on our approach, we do not find evidence of an association of MWI opening with changes in risks of infant mortality or sex ratio in comparison with control areas.
Zhou L, Stamler J, Chan Q, et al., 2019, Salt intake and prevalence of overweight/obesity in Japan, China, the United Kingdom, and the United States: the INTERMAP Study, American Journal of Clinical Nutrition, Vol: 110, Pages: 34-40, ISSN: 1938-3207
BACKGROUND: Several studies have reported that dietary salt intake may be an independent risk factor for overweight/obesity, but results from previous studies are controversial, reflecting study limitations such as use of a single spot urine or dietary recall to estimate daily salt intake rather than 24-h urine collections, and population samples from only a single country or center. OBJECTIVE: The aim of this study was to use data from the International Study of Macro-/Micro-nutrients and Blood Pressure (INTERMAP Study) to explore the relation between dietary salt intake estimated from 2 timed 24-h urine collections and body mass index (BMI; in kg/m2) as well as prevalence of overweight/obesity in Japan, China, the United Kingdom, and the United States. METHODS: Data were from a cross-sectional study of 4680 men and women aged 40-59 y in Japan (n = 1145), China (n = 839), the United Kingdom (n = 501), and the United States (n = 2195). General linear models were used to obtain the regression coefficients (β) of salt intake associated with BMI. Multivariable logistic regression models were used to determine the ORs and 95% CIs of overweight/obesity associated with a 1-g/d higher dietary salt intake. RESULTS: After adjustment for potential confounding factors including energy intake, salt intake 1 g/d higher was associated with BMI higher by 0.28 in Japan, 0.10 in China, 0.42 in the United Kingdom, and 0.52 in the United States, all P values < 0.001. Salt intake 1 g/d higher was associated with odds of overweight/obesity 21% higher in Japan, 4% higher in China, 29% higher in the United Kingdom, and 24% higher in the United States, all P values < 0.05. CONCLUSIONS: Salt intake is positively associated with BMI and the prevalence of overweight/obesity in Japan, China, the United Kingdom, and the United States. This association needs to be further confirmed in well-designed prospective studies with re
Pazoki R, Evangelou E, Mosen-Ansorena D, et al., 2019, PATHWAYS UNDERLYING URINARY SODIUM AND POTASSIUM EXCRETION AND THE LINK TO BLOOD PRESSURE AND CARDIOVASCULAR DISEASE, Journal of Hypertension, Vol: 37, Pages: e74-e74, ISSN: 0263-6352
Gill D, Benyamin B, Moore LSP, et al., 2019, Associations of genetically determined iron status across the phenome: a mendelian randomization study, PLoS Medicine, Vol: 16, ISSN: 1549-1277
BackgroundIron is integral to many physiological processes and variations in its levels, even within the normal range, can have implications for health. The objective of this study was to explore the broad clinical effects of varying iron status.Methods and FindingsGenome-wide association study summary data obtained from 48,972 European individuals (55% female) across 19 cohorts in the Genetics of Iron Status Consortium were used to identify three genetic variants (rs1800562 and rs1799945 in the hemochromatosis gene, and rs855791 in the transmembrane protease serine 6 gene) that associate with increased serum iron, ferritin and transferrin saturation, and decreased transferrin levels, thus serving as instruments for systemic iron status. Phenome-wide association study (PheWAS) of these instruments was performed on 415,482 European individuals (54% female) in the UK Biobank that were aged 40-69 years when recruited from 2006 to 2010, with their genetic data linked to Hospital Episode Statistics from April 1995 to March 2016. Two-sample summary data Mendelian randomization (MR) analysis was performed to investigate the effect of varying iron status on outcomes across the human phenome. MR-PheWAS analysis for the three iron status genetic instruments was performed separately and then pooled by meta-analysis. Correction was made for testing of multiple correlated phenotypes using a 5% false discovery rate threshold. Heterogeneity between MR estimates for different instruments was used to indicate possible bias due to effects of the genetic variants through pathways unrelated to iron status. There were 904 distinct phenotypes included in the MR-PheWAS analyses. After correcting for multiple testing, the three genetic instruments for systemic iron status demonstrated consistent evidence of a causal effect of higher iron status on decreasing risk of traits related to anemia (iron deficiency anemia: odds ratio [OR] scaled to a standard deviation increase in genetically dete
Blangiardo M, Boulieri A, Diggle P, et al., Advances in spatio-temporal models for non-communicable disease surveillance, International Journal of Epidemiology, ISSN: 1464-3685
Surveillance systems are commonly used to provide early warning detection or to assess an impact of an intervention/policy. Traditionally, the methodological and conceptual frameworks for surveillance have been designed for infectious diseases, but the rising burden of non-communicable diseases (NCDs) worldwide suggests a pressing need for surveillance strategies to detect unusual patterns in the data and to help unveil important risk factors in this setting. Surveillance methods need to be able to detect meaningful departures from expectation and exploit dependencies within such data to produce unbiased estimates of risk as well as future forecasts. This has led to the increasing development of a range of space-time methods specifically designed for NCD surveillance.We present an overview of recent advances in spatio-temporal disease surveillance for NCDs using hierarchically specified models. This provides a coherent framework for modelling complex data structures, dealing with data sparsity, exploiting dependencies between data sources and propagating the inherent uncertainties present in both the data and the modelling process. We then focus on three commonly used models within the Bayesian Hierarchical Model (BHM) framework and through a simulation study we compare their performance.We also discuss some challenges faced by researchers when dealing with NCD surveillance, including how to account for false detection and the modifiable areal unit problem. Finally, we consider how to use and interpret the complex models, how model selection may vary depending on the intended user group and how best to communicate results to stakeholders and the general public.
Fecht D, Garwood K, Butters O, et al., Automation of cleaning and reconstructing residential address histories to assign environmental exposures in longitudinal studies, International Journal of Epidemiology, ISSN: 1464-3685
Background: We have developed an open-source ALgorithm for Generating Address Exposures (ALGAE) that cleans residential address records to construct address histories and assign spatially-determined exposuresto cohort participants. The first application of this algorithm was to construct prenatal and early-life air pollution exposure for individuals of the Avon Longitudinal Study of Parents and Children (ALSPAC)in the South West of Englandusingpreviously estimated particulate matter ≤10 μm (PM10) concentrations. Methods: ALSPAC recruited 14,541 pregnant women between 1991and 1992. We assignedtrimester-specific estimated PM10exposures for 12,752 pregnancies,and first year of life exposures for 12,525births, based on maternal residence and residential mobility. Results: Average PM10exposure was32.6 μg/m3(StDev. 3.0 μg/m3) during pregnancy and 31.4 μg/m3(StDev. 2.6 μg/m3) during the first year of life. 6.7% ofwomen changedaddress during pregnancy, and 18.0% moved during first year of lifeof their infant. Exposure differences ranged from -5.3 μg/m3 to 12.4 μg/m3(up to 26% difference) during pregnancy and -7.22 μg/m3to 7.64 μg/m3(up to 27% difference) in the first year of life,when comparing estimated exposure using the address at birth and that assessedusing the complete cleaned address history. For the majority of individualsexposure changed by <5% but some relatively large changes were seen both in pregnancy and infancy.Conclusion: ALGAE provides a generic andadaptable, open-source solution to clean addresses stored in acohort contact database and assign life-stage specific exposureestimates with the potential to reduce exposure misclassification.
de Vries PS, Brown MR, Bentley AR, et al., 2019, Multi-ancestry genome-wide association study of lipid levels incorporating gene-alcohol interactions, American Journal of Epidemiology, Vol: 188, Pages: 1033-1054, ISSN: 1476-6256
An individual's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multi-ancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in Stage 1 (genome-wide discovery) and 66 studies in Stage 2 (focused follow-up), for a total of 394,584 individuals from five ancestry groups. Genetic main and interaction effects were jointly assessed by a 2 degrees of freedom (DF) test, and a 1 DF test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in Stage 1 and were evaluated in Stage 2, followed by combined analyses of Stage 1 and Stage 2. In the combined analysis of Stage 1 and Stage 2, 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2 DF tests, of which 18 were novel. No genome-wide significant associations were found testing the interaction effect alone. The novel loci included several genes (PCSK5, VEGFB, and A1CF) with a putative role in lipid metabolism based on existing evidence from cellular and experimental models.
Yu B, Zanetti KA, Temprosa M, et al., 2019, The Consortium of Metabolomics Studies (COMETS): Metabolomics in 47 Prospective Cohort Studies, American Journal of Epidemiology, Vol: 188, Pages: 991-1012, ISSN: 1476-6256
The Consortium of Metabolomics Studies (COMETS) was established in 2014 to facilitate large-scale collaborative research on the human metabolome and its relationship with disease etiology, diagnosis, and prognosis. COMETS comprises 47 cohorts from Asia, Europe, North America, and South America that together include more than 136,000 participants with blood metabolomics data on samples collected from 1985 to 2017. Metabolomics data were provided by 17 different platforms, with the most frequently used labs being Metabolon, Inc. (14 cohorts), the Broad Institute (15 cohorts), and Nightingale Health (11 cohorts). Participants have been followed for a median of 23 years for health outcomes including death, cancer, cardiovascular disease, diabetes, and others; many of the studies are ongoing. Available exposure-related data include common clinical measurements and behavioral factors, as well as genome-wide genotype data. Two feasibility studies were conducted to evaluate the comparability of metabolomics platforms used by COMETS cohorts. The first study showed that the overlap between any 2 different laboratories ranged from 6 to 121 metabolites at 5 leading laboratories. The second study showed that the median Spearman correlation comparing 111 overlapping metabolites captured by Metabolon and the Broad Institute was 0.79 (interquartile range, 0.56–0.89).
Wuttke M, Li Y, Li M, et al., 2019, A catalog of genetic loci associated with kidney function from analyses of a million individuals, Nature Genetics, Vol: 51, Pages: 957-972, ISSN: 1061-4036
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Elliott P, Aresu M, Gao H, et al., 2019, Use of TETRA personal radios and sickness absence in the Airwave Health Monitoring Study of the British police forces, Environmental Research, Vol: 175, Pages: 148-155, ISSN: 0013-9351
BackgroundTerrestrial Trunked Radio (TETRA) is used for radiocommunications among the British police forces.ObjectivesTo investigate association of personal radio use and sickness absence among police officers and staff from the Airwave Health Monitoring Study.MethodsParticipant-level sickness absence records for 26 forces were linked with personal radio use for 32,102 participants. We used multivariable logistic regression to analyse TETRA usage in year prior to enrolment and sickness absence (lasting more than 7 or 28 consecutive days) in the following year and a zero-inflated negative binomial model for analyses of number of sickness absence episodes of any duration (‘spells’) over the same period. In secondary analyses, we looked at an extended period of observation among a sub-cohort with linked data over time, using Cox proportional hazards regression.ResultsMedian personal radio use (year prior to enrolment) was 29.7 min per month (interquartile range 7.5, 64.7) among users. In the year following enrolment there were 25,655 sickness absence spells among 15,248 participants. There were similar risks of sickness absence lasting more than seven days among users and non-users, although among users risk was higher with greater use, odds ratio = 1.04 (95% confidence interval [CI] 1.02 to 1.06) per doubling of radio use. There was no association for sickness absence of more than 28 days. For sickness absence spells, risk was lower among users than non-users (incidence rate ratio = 0.91; 95% CI 0.75 to 1.11), again with higher risk among users for greater radio use. There was no association between radio use and sickness absence in secondary analyses.DiscussionThere were similar or lower risks of sickness absence in TETRA radio users compared with non-users. Among users, the higher risk of sickness absence with greater radio use may reflect working pattern differences among police personnel rather than effects of radiofrequency exposure.
Bixby H, Bentham J, Zhou B, et al., 2019, Rising rural body-mass index is the main driver of the global obesity epidemic, Nature, Vol: 569, Pages: 260-264, ISSN: 0028-0836
Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
Davies G, Lam M, Harris SE, et al., 2019, Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function (vol 9, 2098, 2018), NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723
McCrory C, Leahy S, Ribeiro AI, et al., 2019, Maternal educational inequalities in measured body mass index trajectories in three European countries, PAEDIATRIC AND PERINATAL EPIDEMIOLOGY, Vol: 33, Pages: 226-237, ISSN: 0269-5022
Fiorito G, McCrory C, Robinson O, et al., 2019, Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis, Aging, Vol: 11, Pages: 2045-2070, ISSN: 1945-4589
Differences in health status by socioeconomic position (SEP) tend to be more evident at older ages, suggesting the involvement of a biological mechanism responsive to the accumulation of deleterious exposures across the lifespan. DNA methylation (DNAm) hasbeen proposed as a biomarker of biological aging that conserves memory of endogenous and exogenous stress during life. We examined the association of education level, as an indicator of SEP, and lifestyle-related variables with four biomarkers of age-dependent DNAm dysregulation: the total number of stochastic epigenetic mutations (SEMs) and three epigenetic clocks (Horvath, Hannum and Levine), in 18 cohorts spanning 12 countries. The four biological aging biomarkers were associated with education and different sets of risk factors independently,and themagnitude of the effectsdiffereddepending on the biomarker and the predictor. On average, the effect of low education on epigenetic aging was comparable with those of other lifestyle-related risk factors (obesity, alcohol intake), with the exception ofsmoking, which hada significantly stronger effect. Our study shows that low education is an independent predictor of accelerated biological (epigenetic) aging and that epigenetic clocks appear to be good candidates for disentangling the biological pathways underlying social inequalities in healthy aging and longevity.
Piel F, Parkes B, Hambly P, et al., The Rapid Inquiry Facility 4.0: an open access tool for Environmental Public Health Tracking, International Journal of Epidemiology, ISSN: 1464-3685
The Rapid Inquiry Facility 4.0 (RIF) is a new user-friendly and open-access tool, developed by the UK Small Area Health Statistics Unit (SAHSU), to facilitate environment public health tracking (EPHT) or surveillance (EPHS). The RIF is designed to help public health professionals and academics to rapidly perform exploratory investigations of health and environmental data at the small-area level (e.g. postcode or detailed census areas) in order to identify unusual signals, such as disease clusters, and potential environmental hazards, whether localised (e.g. industrial site) or widespread (e.g. air and noise pollution). The RIF allows the use of advanced disease mapping methods, including Bayesian small-area smoothing, and complex risk analysis functionalities, while accounting for confounders. The RIF could be particularly useful to monitor spatio-temporal trends in mortality and morbidity associated with cardiovascular diseases, cancers, diabetes and chronic lung diseases, or to conduct local or national studies on air pollution, flooding, low-magnetic fields or nuclear powerplants.
Wen X, Zhou L, Stamler J, et al., 2019, Agreement between 24-h dietary recalls and 24-h urine collections for estimating sodium intake in China, Japan, UK, USA: the International Study of Macro- and Micro-nutrients and Blood Pressure, Journal of Hypertension, Vol: 37, Pages: 814-819, ISSN: 0263-6352
OBJECTIVE: The present study aims to compare 24-h dietary recalls with 24-h urine collections for the estimation of sodium intake at both population and individual levels in China, Japan, the United Kingdom (UK), and the United States of America (USA), using data from the International Study of Macro- and Micro-nutrients and Blood Pressure (INTERMAP). METHODS: Mean differences between 24-h dietary recalls and 24-h urine collections were calculated for their agreement in estimating sodium intake at the population level; relative and absolute differences as well as misclassification of salt intake groups (salt intake <6, 6-8.9, 9-11.9, 12-14.9, and ≥15 g/day) were used to determine the agreement at the individual level. RESULTS: The mean differences (95% CI) between dietary recalls and urine collections for China, Japan, UK, and USA were -54.0 (-59.8, -48.3), 3.9 (0.6, 7.2), 2.9 (-1.8, 7.6), and -3.5 (-5.8, -1.1) mmol/day, respectively. The proportions of individual relative differences beyond ±40% were 34.3% for China, 16.9% for Japan, 24.2% for UK, and 21.3% for USA; the proportions of individual absolute differences greater than 51.3 mmol/day (3 g salt) were 58.6% for China, 32.8% for Japan, 25.4% for UK, and 31.9% for USA. The rate for misclassification of salt intake groups at individual level for China, Japan, UK, and USA were 71.4, 60.9, 58.7, and 60.0%, respectively. CONCLUSION: The 24-h dietary recalls demonstrate greater agreement with the 24-h urine collections in estimating population sodium intake for Japan, UK, and USA, compared with China. The 24-h dietary recall has poor performance in assessing individual sodium intake in these four countries.
Mireku MO, Barker MM, Mutz J, et al., 2019, Processed data on the night-time use of screen-based media devices and adolescents’ sleep quality and health-related quality of life, Data in Brief, Vol: 23, ISSN: 2352-3409
The data presented in this article relate to the research article entitled “Night-time screen-based media device use and adolescents' sleep and health-related quality of life”. The present data reports findings from the investigation of the relationship between night-time screen-based media devices (SBMD) use and both sleep quality and health-related quality of life (HRQoL) among 11 to 12-year-olds. Baseline data from a large cohort of 6,616 adolescents from 39 schools in and around London, UK, participating in the Study of Cognition Adolescents and Mobile Phone (SCAMP) were analysed. Self-report data on adolescents’ use of any SBMD (mobile phone, tablet, laptop, television etc.) were the main exposures of interest. Mobile phone and television were the most commonly used portable and non-portable device, respectively. Sleep variables were derived from self-reported weekday and/or weekend bedtime, sleep onset latency (SOL) and wake time. Sleep quality was assessed using four standardised dimensions from the Swiss Health Survey. HRQoL was estimated using the KIDSCREEN-10 questionnaire.
Bentley AR, Sung YJ, Brown MR, et al., 2019, Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids, Nature Genetics, Vol: 51, Pages: 636-648, ISSN: 1061-4036
The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene–smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.
Middeldorp CM, Felix JF, Mahajan A, et al., 2019, The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects, European Journal of Epidemiology, Vol: 34, Pages: 279-300, ISSN: 0393-2990
The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Mireku MO, Barker M, Mutz J, et al., 2019, Night-time screen-based media device use and adolescents’ sleep and health-related quality of life, Environment International, Vol: 124, Pages: 66-78, ISSN: 0160-4120
ObjectiveThe present study investigates the relationship between night-time screen-based media devices (SBMD) use, which refers to use within 1 h before sleep, in both lit and dark rooms, and sleep outcomes and health-related quality of life (HRQoL) among 11 to 12-year-olds.MethodsWe analysed baseline data from a large cohort of 6616 adolescents from 39 schools in and around London, United Kingdom, participating in the Study of Cognition Adolescents and Mobile Phone (SCAMP). Adolescents self-reported their use of any SBMD (mobile phone, tablet, laptop, television etc.). Sleep variables were derived from self-reported weekday and/or weekend bedtime, sleep onset latency (SOL) and wake time. Sleep quality was assessed using four standardised dimensions from the Swiss Health Survey. HRQoL was estimated using the KIDSCREEN-10 questionnaire.ResultsOver two-thirds (71.5%) of adolescents reported using at least one SBMD at night-time, and about a third (32.2%) reported using mobile phones at night-time in darkness. Night-time mobile phone and television use was associated with higher odds of insufficient sleep duration on weekdays (Odds Ratio, OR = 1.82, 95% Confidence Interval, CI [1.59, 2.07] and OR = 1.40, 95% CI [1.23, 1.60], respectively). Adolescents who used mobile phones in a room with light were more likely to have insufficient sleep (OR = 1.32, 95% CI [1.10, 1.60]) and later sleep midpoint (OR = 1.64, 95% CI [1.37, 1.95]) on weekends compared to non-users. The magnitude of these associations was even stronger for those who used mobile phones in darkness for insufficient sleep duration on weekdays (OR = 2.13, 95% CI [1.79, 2.54]) and for later sleep midpoint on weekdays (OR = 3.88, 95% CI [3.25, 4.62]) compared to non-users. Night-time use of mobile phones was associated with lower HRQoL and use in a dark room was associated with even lower KIDSCREEN-10 score (β = –1.18, 95% CI [–1.85, –0.52]) compared to no use.ConclusionsWe found consistent
Justice AE, Karaderi T, Highland HM, et al., 2019, Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution, Nature Genetics, Vol: 51, Pages: 452-469, ISSN: 1061-4036
Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
Hodgson S, Fecht D, Gulliver J, et al., Availability, access, analysis and dissemination of small area data, International Journal of Epidemiology, ISSN: 1464-3685
In this era of ‘big data’, there is growing recognition of the value of environmental, health, social and demographic data for research. Open government data initiatives are growing in number and in terms of content. Remote sensing data are finding widespread use in environmental research, including in low- and middle-income settings. While our ability to study environment and health associations across countries and continents grows, data protection rules and greater patient control over the use of their data present new challenges to using health data in research. Innovative tools that circumvent the need for the physical sharing of data by supporting non-disclosive sharing of information, or that permit spatial analysis without researchers needing access to underlying patient data can be used to support analyses while protecting data confidentiality. User-friendly visualisations, allowing small area data to be seen and understood by non-expert audiences are revolutionising public and researcher interactions with data. The UK Small Area Health Statistics Unit’s Environment and Health Atlas for England and Wales, and the US National Environmental Public Health Tracking Network offer good examples. Open data facilitates user-generated outputs, and ‘mash-ups’, and user generated inputs from social media, mobile devices, and wearable tech are new data streams which will find utility in future studies, and bring novel dimensions with respect to ethical use of small area data.
Müller CP, Chu C, Qin L, et al., 2019, The cortical neuroimmune regulator TANK affects emotional processing and enhances alcohol drinking: a translational study, Cerebral Cortex, Vol: 29, Pages: 1736-1751, ISSN: 1047-3211
Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-κB activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 × 10-19) and regional methylation (P = 5.90 × 10-25). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-κB. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
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