Imperial College London

ProfessorPaulElliott

Faculty of MedicineSchool of Public Health

Chair in Epidemiology and Public Health Medicine
 
 
 
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Contact

 

+44 (0)20 7594 3328p.elliott Website

 
 
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Assistant

 

Miss Jennifer Wells +44 (0)20 7594 3328

 
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Location

 

154Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

616 results found

Elliott J, Bodinier B, Bond TA, Chadeau-Hyam M, Evangelou E, Moons KGM, Dehghan A, Muller DC, Elliott P, Tzoulaki Iet al., 2020, Predictive Accuracy of a Polygenic Risk Score-Enhanced Prediction Model vs a Clinical Risk Score for Coronary Artery Disease, JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, Vol: 323, Pages: 636-645, ISSN: 0098-7484

Journal article

Aljuraiban GS, Pertiwi K, Stamler J, Chan Q, Geleijnse JM, Van Horn L, Daviglus ML, Elliott P, Oude Griep LM, INTERMAP Research Groupet al., 2020, Potato consumption, by preparation method and meal quality, with blood pressure and body mass index: The INTERMAP study, Clinical Nutrition, ISSN: 0261-5614

BACKGROUND AND AIMS: Previous studies have reported associations between higher potato intake and higher blood pressure (BP) and/or risk of hypertension and obesity. These studies rarely considered preparation methods of potatoes, overall dietary pattern or the nutrient quality of the meals. These factors may affect the association of potato intake with BP and body mass index (BMI). This study investigated potato consumption by amount, type of processing, overall dietary pattern, and nutrient quality of the meals in relation to BP and BMI. METHODS: Cross-sectional analyses were conducted among 2696 participants aged 40-59 y in the US and UK samples of the International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP). Nutrient quality of individual food items and the overall diet was assessed with the Nutrient-Rich Foods (NRF) index. RESULTS: No associations with BP or BMI were found for total potato intake nor for boiled, mashed, or baked potatoes or potato-based mixed dishes. In US women, higher intake of fried potato was associated with 2.29 mmHg (95% CI: 0.55, 3.83) higher systolic BP and with 1.14 mmHg (95% CI: 0.10, 2.17) higher diastolic BP, independent of BMI. Higher fried potato consumption was directly associated with a +0.86 kg/m2 difference in BMI (95% CI: 0.24, 1.58) in US women. These associations were not found in men. Higher intakes of fried potato meals with a lower nutritional quality (NRF index≤ 2) were positively associated with systolic (3.88 mmHg; 95% CI: 2.63, 5.53) and diastolic BP (1.62 mmHg; 95% CI: 0.48, 2.95) in US women. No associations with BP were observed for fried potato meals with a higher nutritional quality (NRF index> 2). CONCLUSIONS: Fried potato was directly related to BP and BMI in women, but non-fried potato was not. Poor-nutrient quality meals were associated with intake of fried potatoes and higher BP, suggesting that accompanied dietary choices are key mediators of

Journal article

Cai Y, Blangiardo M, de Hoogh K, Gulliver J, Morley D, Doiron D, Elliott P, Hansell A, Hodgson Set al., 2020, Road traffic noise, air pollution and cardiorespiratory Health in European Cohorts: A harmonised approach in the BioShare project, Pages: 137-142

Copyright © (2015) by EAA-NAG-ABAV, All rights reserved Background and aims: Few studies have investigated joint effects of road traffic noise and air pollution on cardiorespiratory outcomes. This project aims to quantify the joint and separate effects of both exposures on prevalent and incident cardiovascular disease and asthma as part of the EU-funded BioSHaRE project involving five European cohorts (EPIC-Oxford, EPIC-Turin, HUNT, Lifelines, UK Biobank). Methods: Health outcomes have been ascertained by self-report (prevalence) and medical record (incidence) and retrospectively harmonised across cohorts. Residential road traffic noise exposures for each participant are estimated using a European noise model based on Common Noise Assessment Methods in Europe (CNOSSOS-EU). Road traffic air pollution estimates at home address were derived from Land Use Regression models. Cross-sectional and incident epidemiological analyses are in progress, using individual level data, virtually pooled using DataSHIELD methodology. Results: In total, 742,950 men and women are included from all five cohorts, mostly >40 years. Prevalence of self-reported myocardial infarction from these five cohorts is 2.1% (N=15,031) while prevalence of self-reported stroke is 1.4% (N=10,077). Initial pooled analysis of EPIC-Oxford, HUNT and Lifelines showed median day-time (07:00-19:00) noise estimate of 51.8 dB(A) and night-time (23:00-07:00) noise estimate of 43.5 dB(A). Correlations between noise estimates and NO2 are generally low (r=0.1 to 0.4). Conclusions: Pooling of individual level harmonised data from established cohorts offers the large sample sizes and exposure variations needed to investigate effects of road traffic noise and ambient air pollution on cardio-respiratory diseases.

Conference paper

Jaime Miranda J, Carrillo-Larco RM, Ferreccio C, Hambleton IR, Lotufo PA, Nieto-Martinez R, Zhou B, Bentham J, Bixby H, Hajifathalian K, Lu Y, Taddei C, Abarca-Gomez L, Acosta-Cazares B, Aguilar-Salinas CA, Andrade DS, Assuncao MCF, Barcelo A, Barros AJD, Barros MVG, Bata I, Batista RL, Benet M, Bernabe-Ortiz A, Bettiol H, Boggia JG, Boissonnet CP, Brewster LM, Cameron C, Candido APC, Cardoso VC, Chan Q, Christofaro DG, Confortin SC, Craig CL, d'Orsi E, Delisle H, de Oliveira PD, Dias-da-Costa JS, Diaz A, Donoso SP, Elliott P, Escobedo-de la Pena J, Ferguson TS, Fernandes RA, Ferrante D, Monterubio Flores E, Francis DK, Franco MDC, Fuchs FD, Fuchs SC, Goltzman D, Goncalves H, Gonzalez-Rivas JP, Bonet Gorbea M, Gregor RD, Guerrero R, Guimaraes AL, Gulliford MC, Gutierrez L, Hernandez Cadena L, Herrera VM, Hopman WM, Horimoto ARVR, Hormiga CM, Horta BL, Howitt C, Irazola VE, Magaly Jimenez-Acosta S, Joffres M, Kolsteren P, Landrove O, Li Y, Lilly CL, Fernanda Lima-Costa M, Louzada Strufaldi MW, Machado-Coelho GLL, Makdisse M, Margozzini P, Marques LP, Martorell R, Matijasevich A, Posso AJMD, McFarlane SR, McLean SB, Menezes AMB, Miquel JF, Mohanna S, Monterrubio EA, Moreira LB, Morejon A, Motta J, Neal WA, Nervi F, Noboa OA, Ochoa-Aviles AM, Anselmo Olinto MT, Oliveira IO, Ono LM, Ordunez P, Ortiz AP, Otero JA, Palloni A, Peixoto SV, Pereira AC, Perez CM, Reina DAR, Ribeiro R, Ritti-Dias RM, Rivera JA, Robitaille C, Rodriguez-Villamizar LA, Rojas-Martinez R, Roy JGR, Rubinstein A, Sandra Ruiz-Betancourt B, Salazar Martinez E, Sanchez-Abanto J, Santos IS, dos Santos RN, Scazufca M, Schargrodsky H, Silva AM, Santos Silva DA, Stein AD, Suarez-Medina R, Tarqui-Mamani CB, Tulloch-Reid MK, Ueda P, Ugel EE, Valdivia G, Varona P, Velasquez-Melendez G, Verstraeten R, Victora CG, Wanderley RS, Wang M-D, Wilks RJ, Wong-McClure RA, Younger-Coleman NO, Zuniga Cisneros J, Danaei G, Stevens GA, Riley LM, Ezzati M, Di Cesare Met al., 2020, Trends in cardiometabolic risk factors in the Americas between 1980 and 2014: a pooled analysis of population-based surveys, The Lancet Global Health, Vol: 8, Pages: E123-E133, ISSN: 2214-109X

BackgroundDescribing the prevalence and trends of cardiometabolic risk factors that are associated with non-communicable diseases (NCDs) is crucial for monitoring progress, planning prevention, and providing evidence to support policy efforts. We aimed to analyse the transition in body-mass index (BMI), obesity, blood pressure, raised blood pressure, and diabetes in the Americas, between 1980 and 2014.MethodsWe did a pooled analysis of population-based studies with data on anthropometric measurements, biomarkers for diabetes, and blood pressure from adults aged 18 years or older. A Bayesian model was used to estimate trends in BMI, raised blood pressure (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg), and diabetes (fasting plasma glucose ≥7·0 mmol/L, history of diabetes, or diabetes treatment) from 1980 to 2014, in 37 countries and six subregions of the Americas.Findings389 population-based surveys from the Americas were available. Comparing prevalence estimates from 2014 with those of 1980, in the non-English speaking Caribbean subregion, the prevalence of obesity increased from 3·9% (95% CI 2·2–6·3) in 1980, to 18·6% (14·3–23·3) in 2014, in men; and from 12·2% (8·2–17·0) in 1980, to 30·5% (25·7–35·5) in 2014, in women. The English-speaking Caribbean subregion had the largest increase in the prevalence of diabetes, from 5·2% (2·1–10·4) in men and 6·4% (2·6–10·4) in women in 1980, to 11·1% (6·4–17·3) in men and 13·6% (8·2–21·0) in women in 2014). Conversely, the prevalence of raised blood pressure has decreased in all subregions; the largest decrease was found in North America from 27·6% (22·3–33·2) in men and 19·9% (15·8–24·4) in women in 1980, to 15·

Journal article

Gulliver J, Morley D, Fecht D, Fabbri F, Elliott P, Hansell A, Hodgson S, de Hoogh K, Bell M, Goodman Pet al., 2020, Feasibility study for using the CNOSSOS-EU road traffic noise prediction model with low resolution inputs for exposure estimation on a Europe-wide scale, Pages: 481-486

Copyright © (2015) by EAA-NAG-ABAV, All rights reserved A noise model based on the CNOSSOS-EU method was developed to estimate exposures to road traffic noise at individual address locations for studies of noise and health in European cohorts in the EU FP7 BioSHaRE project. We assessed the loss in model performance from necessarily (i.e. at national scale) using low resolution data on traffic flows, road geography and land cover. To assess the feasibility of this approach in terms of the loss of model performance, we applied CNOSSOS-EU with different combinations of high- and low-resolution inputs (e.g. high resolution road geography with low resolution land cover) and compared noise level estimates with measurements of LAeq1hr from 38 locations in Leicester, a medium sized city in the UK. The lowest resolution model performed reasonably well in terms of correlation [rs = 0.75; p = 0.000)] but with relatively large model errors [RMSE = 4.46 dB(A)]. For a sample of postcode (zip code) locations (n=721) in Leicester, in comparing output from Model A (highest resolution) and Model F (lowest resolution), 81.8% and 72.8% of exposure estimates remained in the lowest and highest of three equal exposure categories, respectively.

Conference paper

Cade J, Wark P, Frost G, Alwan N, Carter M, Elliott P, Ford H, Hancock N, Morris M, Mulla Z, Noorwali E, Petropoulou A, Potter G, Riboli E, Hardie L, Greenwood Det al., 2020, Validation of an automated online 24-hour recall (myfood24) using nutrient biomarkers provides similar results to a traditional interviewer administered recall, Publisher: CAMBRIDGE UNIV PRESS, Pages: E391-E391, ISSN: 0029-6651

Conference paper

Carter E, Yan L, Fu Y, Robinson B, Kelly F, Elliott P, Wu Y, Zhao L, Ezzati M, Yang X, Chan Q, Baumgartner Jet al., 2020, Household transitions to clean energy in a multi-provincial cohort study in China, Nature Sustainability, Vol: 3, Pages: 42-50, ISSN: 2398-9629

Household solid fuel (biomass, coal) burning contributes to climate change and is a leading health risk factor. How and why households stop using solid fuel stoves after adopting clean fuels has not been studied. We assessed trends in the uptake, use, and suspension of household stoves and fuels in a multi-provincial cohort study of 753 Chinese adults and evaluated determinants of clean fuel uptake and solid fuel suspension. Over one-third (35%) and one-fifth (17%) of participants suspended use of solid fuel for cooking and heating, respectively, during the past 20 years. Determinants of solid fuel suspension (younger age, widowed) and of earlier suspension (younger age, higher education, and poor self-reported health status) differed from the determinants of clean fuel uptake (younger age, higher income, smaller households, and retired) and of earlier adoption (higher income). Clean fuel adoption and solid fuel suspension warrant joint consideration as indicators of household energy transition. Household energy research and planning efforts that more closely examine solid fuel suspension may accelerate household energy transitions that benefit climate and human health.

Journal article

Parkes B, Hansell AL, Ghosh RE, Douglas P, Fecht D, Wellesley D, Kurinczuk JJ, Rankin J, de Hoogh K, Fuller GW, Elliott P, Toledano MBet al., 2020, Risk of congenital anomalies near municipal waste incinerators in England and Scotland, Retrospective population-based cohort study, Vol: 134, ISSN: 0160-4120

Background: Few studies have investigated congenital anomalies in relation to municipal waste incinerators (MWIs) and results are inconclusive. Objectives: To conduct a national investigation into the risk of congenital anomalies in babies born to mothers living within 10 km of an MWI associated with: i) modelled concentrations of PM10 as a proxy for MWI emissions more generally and; ii) proximity of residential postcode to nearest MWI, in areas in England and Scotland that are covered by a congenital anomaly register. Methods: Retrospective population-based cohort study within 10 km of 10 MWIs in England and Scotland operating between 2003 and 2010. Exposure was proximity to MWI and log of daily mean modelled ground-level particulate matter ≤10 μm diameter (PM10) concentrations. Results: Analysis included 219,486 births, stillbirths and terminations of pregnancy for fetal anomaly of which 5154 were cases of congenital anomalies. Fully adjusted odds ratio (OR) per doubling in PM10 was: 1·00 (95% CI 0·98–1·02) for all congenital anomalies; 0·99 (0·97–1·01) for all congenital anomalies excluding chromosomal anomalies. For every 1 km closer to an MWI adjusted OR was: 1·02 (1·00–1·04) for all congenital anomalies combined; 1·02 (1·00–1·04) for all congenital anomalies excluding chromosomal anomalies; and, for specific anomaly groups, 1·04 (1·01–1·08) for congenital heart defect sand 1·07 (1·02–1·12) for genital anomalies. Discussion: We found no increased risk of congenital anomalies in relation to modelled PM10 emissions, but there were small excess risks associated with congenital heart defects and genital anomalies in proximity to MWIs. These latter findings may well reflect incomplete control for confounding, but a possible causal effect cannot be excluded.

Journal article

Wong JYY, Bassig BA, Loftfield E, Hu W, Freedman ND, Ji B-T, Elliott P, Silverman DT, Chanock SJ, Rothman N, Lan Qet al., 2019, White blood cell count and risk of incident lung cancer in the UK Biobank, JNCI Cancer Spectrum, Vol: 4, Pages: 1-9, ISSN: 2515-5091

BackgroundThe contribution of measurable immunological/inflammatory parameters to lung cancer development remains unclear, particularly among never-smokers. We investigated the relationship between total and differential white blood cell (WBC) counts and incident lung cancer risk overall and among subgroups defined by smoking status and sex in the United Kingdom (UK).MethodsWe evaluated 424,407 adults aged 37-73 years from the UK Biobank. Questionnaires, physical measurements, and blood were administered/collected at baseline in 2006-2010. Complete blood cell counts were measured using standard methods. Lung cancer diagnoses and histological classifications were obtained from cancer registries. Multivariable Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of incident lung cancer in relation to quartiles (Q) of total WBC and subtype-specific counts, with Q1 as the reference.ResultsThere were 1,493 incident cases diagnosed over an average 7-year follow-up. Overall, the highest quartile of total WBC count was significantly associated with elevated lung cancer risk (HRQ4=1.67, 95% CI:1.41-1.98). Among women, increased risks were found in current-smokers (ncases/n=244/19,464, HRQ4=2.15, 95% CI:1.46-3.16), former-smokers (ncases/n=280/69,198, HRQ4=1.75, 95% CI:1.24-2.47), and never-smokers without environmental tobacco smoke exposure (ncases/n=108/111,294, HRQ4=1.93, 95% CI:1.11-3.35). Among men, stronger associations were identified in current-smokers (ncases/n=329/22,934, HRQ4=2.95, 95% CI:2.04-4.26) and former-smokers (ncases/n= 358/71,616, HRQ4=2.38, 95% CI:1.74-3.27) but not in never-smokers. Findings were similar for lung adenocarcinoma and squamous cell carcinoma and were driven primarily by elevated neutrophil fractions.ConclusionsElevated WBCs could potentially be one of many important markers for increased lung cancer risk, especially among never-smoking women and ever-smoking men.

Journal article

Gibson R, Lau C, Loo RL, Ebbels T, Chekmeneva E, Dyer A, Miura K, Ueshima H, Zhao L, Daviglus M, Stamler J, Van Horn L, Elliott P, Holmes E, Chan Qet al., 2019, The association of fish consumption and its urinary metabolites with cardiovascular risk factors: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP), American Journal of Clinical Nutrition, Vol: 111, Pages: 280-290, ISSN: 0002-9165

BackgroundResults from observational studies regarding associations between fish (including shellfish) intake and cardiovascular disease risk factors, including blood pressure (BP) and BMI, are inconsistent.ObjectiveTo investigate associations of fish consumption and associated urinary metabolites with BP and BMI in free-living populations.MethodsWe used cross-sectional data from the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP), including 4680 men and women (40–59 y) from Japan, China, the United Kingdom, and United States. Dietary intakes were assessed by four 24-h dietary recalls and BP from 8 measurements. Urinary metabolites (2 timed 24-h urinary samples) associated with fish intake acquired from NMR spectroscopy were identified. Linear models were used to estimate BP and BMI differences across categories of intake and per 2 SD higher intake of fish and its biomarkers.ResultsNo significant associations were observed between fish intake and BP. There was a direct association with fish intake and BMI in the Japanese population sample (P trend = 0.03; fully adjusted model). In Japan, trimethylamine-N-oxide (TMAO) and taurine, respectively, demonstrated area under the receiver operating characteristic curve (AUC) values of 0.81 and 0.78 in discriminating high against low fish intake, whereas homarine (a metabolite found in shellfish muscle) demonstrated an AUC of 0.80 for high/nonshellfish intake. Direct associations were observed between urinary TMAO and BMI for all regions except Japan (P < 0.0001) and in Western populations between TMAO and BP (diastolic blood pressure: mean difference 1.28; 95% CI: 0.55, 2.02 mmHg; P = 0.0006, systolic blood pressure: mean difference 1.67; 95% CI: 0.60, 2.73 mmHg; P = 0.002).ConclusionsUrinary TMAO showed a stronger association with fish intake in the Japanese compared with the Western population sample. Urinary TMAO was directly associated with BP in the Western but not the Japanese popula

Journal article

Kaura A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, Omigie J, Shah A, Channon K, Weber J, Thursz M, Elliott P, Hemingway H, Williams B, Asselbergs F, OSullivan M, Kharbanda R, Lord G, Melikian N, Patel R, Perera D, Shah A, Francis D, Mayet Jet al., 2019, Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres, BMJ-British Medical Journal, Vol: 367, ISSN: 1756-1833

ObjectiveTo determine the relation between age and troponinlevel and its prognostic implication.DesignRetrospective cohort study.SettingFive cardiovascular centres in the UK National Institutefor Health Research Health Informatics Collaborative(UK-NIHR HIC).Participants257948 consecutive patients undergoing troponintesting for any clinical reason between 2010 and2017.Main outcome measureAll cause mortality.Results257948 patients had troponin measured during thestudy period. Analyses on troponin were performedusing the peak troponin level, which was the highesttroponin level measured during the patient’s hospitalstay. Troponin levels were standardised as a multipleof each laboratory’s 99th centile of the upper limitof normal (ULN). During a median follow-up of 1198days (interquartile range 514-1866 days), 55850(21.7%) deaths occurred. A positive troponin result(that is, higher than the upper limit of normal)signified an overall 3.2-fold higher mortality hazard(95% confidence interval 3.1-fold to 3.2-fold) overthree years. The mortality hazard varied markedly withage, from 10.6-fold (8.5-fold to 13.3-fold) in 18-29year olds to 1.5 (1.4 to 1.6) in those older than 90.A positive troponin result was associated with anapproximately 15 percentage points higher absolutethree year mortality across all age groups. The excessmortality with a positive troponin result was heavilyconcentrated in the first few weeks. Results wereanalysed using multivariable adjusted restrictedcubic spline Cox regression. A direct relation wasseen between troponin level and mortality in patientswithout acute coronary syndrome (ACS, n=120049),whereas an inverted U shaped relation was foundin patients with ACS (n=14468), with a paradoxicaldecline in mortality at peak troponin levels >70xULN.In the group with ACS, the inverted U shaped relationpersisted after multivariable adjustment in those whowere managed invasively; however, a direct positiverelation was found between troponin level

Journal article

Noordam R, Evangelou E, Elliott P, Redline Set al., 2019, Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration, Nature Genetics, Vol: 10, ISSN: 1061-4036

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

Journal article

Clark DW, Zhang W, Gao H, Afaq S, Elliott P, Elliott J, Poulter N, Scott W, Sever P, Tzoulaki I, Lehne B, Chambers J, Evangelou E, Kooner J, Walters R, Wilson Jet al., 2019, Associations of autozygosity with a broad range of human phenotypes, Nature Communications, Vol: 10, ISSN: 2041-1723

In many species, the offspring of related parents suffer reduced vigor, survival and reproductive success, a phenomenon known as inbreeding depression1. In humans, the importance of this effect has remained unclear2, partly because reproduction between close relatives is both rare in many cultures and frequently associated with confounding social factors3. Here, using genomic inbreeding coefficients4 (FROH) for >1.3 million individuals, we show that FROH is significantly associated (P < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. Increased FROH is associated with reduced reproductive success (decreased number and likelihood of having children, older age at first sex and first birth, decreased number of sexual partners), as well as reduced risk-taking behaviour (alcohol intake, ever-smoked, self-reported risk taking) and increased disease risk (self-reported overall health, and risk factors including grip strength and heart rate). The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. These effects are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants causing inbreeding depression are predominantly rare. For a subset of traits, the effect of FROH differs significantly between men and women. Indeed, an increased FROH is associated with decreased total and LDL cholesterol in men, raising the possibility that increases in these traits may have benefited evolutionary fitness, despite being known coronary risk factors. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of environmental confounding. We conclude that inbreeding depression influences a broad range of human phenotypes through the action of rare, recessive variants.

Journal article

Yan L, Carter E, Fu Y, Guo D, Huang P, Xie G, Xie W, Zhu Y, Kelly F, Elliott P, Zhao L, Yang X, Ezzati M, Wu Y, Baumgartner J, Chan Qet al., 2019, Study protocol: The INTERMAP China Prospective (ICP) study, Wellcome Open Research, Vol: 4, Pages: 154-154

<ns4:p><ns4:bold>Background:</ns4:bold> Unfavourable blood pressure (BP) level is an established risk factor for cardiovascular diseases (CVD), while the exact underlying reasons for unfavourable BP are poorly understood.  The INTERMAP China Prospective (ICP) Study is a prospective cohort to investigate the relationship of environmental and nutritional risk factors with key indicators of vascular function including BP, arterial stiffness, and carotid-intima media thickness.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> A total of 839 Chinese participants aged 40-59 years from three diverse regions of China were enrolled in INTERMAP in 1997/98; data collection included repeated BP measurements, 24-hour urine specimens, and 24-hour dietary recalls.  In 2015/16, 574 of these 839 persons were re-enrolled along with 208 new participants aged 40-59 years that were randomly selected from the same study villages.  Participant’s environmental and dietary exposures and health outcomes were assessed in this open cohort study, including BP, 24-hour dietary recalls, personal exposures to air pollution, grip strength, arterial stiffness, carotid-media thickness and plaques, cognitive function, and sleep patterns.  Serum and plasma specimens were collected with 24-hour urine specimens.</ns4:p><ns4:p> <ns4:bold>Discussion:</ns4:bold>  Winter and summer assessments of a comprehensive set of vascular indicators and their environmental and nutritional risk factors were conducted with high precision.  We will leverage advances in exposome research to identify biomarkers of exposure to environmental and nutritional risk factors and improve our understanding of the mechanisms and pathways of their hazardous cardiovascular effects.  The ICP Study is observational by design, thus subject to several biases including selection bias (e.g., loss to follow-up), information bias (e.g., measu

Journal article

Yan L, Wen X, Dyer AR, Chen H, Zhou L, Elliott P, Wu Y, Chan Q, Zhao Let al., 2019, Development of equations for converting random-zero to automated oscillometric blood pressure values, Wellcome Open Research, Vol: 4, Pages: 146-146

<ns4:p><ns4:bold>Background: </ns4:bold>This study aimed to collect data to compare blood pressure values between random-zero sphygmomanometers and automated oscillometric devices and generate equations to convert blood pressure values from one device to the other.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> Omron HEM-907, a widely used automated oscillometric device in many epidemiologic surveys and cohort studies, was compared here with random-zero sphygmomanometers. In total, 201 participants aged 40-79 years (37% men) were enrolled and randomly assigned to one of two groups, with blood pressure measurement first taken by automated oscillometric devices or by random-zero sphygmomanometers. The study design enabled comparisons of blood pressure values between random-zero sphygmomanometers and two modes of this automated oscillometric device (automated and manual), and assessment of effects of measurement order on blood pressure values.</ns4:p><ns4:p> <ns4:bold>Results: </ns4:bold>Among all participants, mean blood pressure levels were the lowest when measured with random-zero sphygmomanometers compared with both modes of automated oscillometric devices. Several variables, including age and gender, were found to contribute to the blood pressure differences between random-zero sphygmomanometers and automated oscillometric devices. Equations were developed using multiple linear regression after taking those variables into account to convert blood pressure values by random-zero sphygmomanometers to automated oscillometric devices.</ns4:p><ns4:p> <ns4:bold>Conclusions: </ns4:bold>Equations developed in this study could be used to compare blood pressure values between epidemiologic and clinical studies or identify shift of blood pressure distribution over time using different devices for blood pressure measurements.</ns4:p>

Journal article

Greenwood DC, Hardie LJ, Frost GS, Alwan NA, Bradbury KE, Carter M, Elliott P, Evans CEL, Ford HE, Hancock N, Key TJ, Liu B, Morris MA, Mulla UZ, Petropoulou K, Potter GDM, Riboli E, Young H, Wark PA, Cade JEet al., 2019, Validation of the Oxford WebQ Online 24-hour dietary questionnaire using biomarkers, American Journal of Epidemiology, Vol: 188, Pages: 1858-1867, ISSN: 1476-6256

Oxford WebQ is an online dietary questionnaire covering 24 hours, appropriate for repeated administration in large-scale prospective studies including UK Biobank and the Million Women Study. We compared performance of the Oxford WebQ and a traditional interviewer-administered multi-pass 24-hour recall against biomarkers for protein, potassium and total sugar intake, and total energy expenditure estimated by accelerometry. 160 participants were recruited between 2014 and 2016 in London, UK, and measured at 3 non-consecutive time-points. The measurement error model simultaneously compared all 3 methods. Attenuation factors for protein, potassium, sugars and total energy intake estimated by the mean of 2 Oxford WebQs were 0.37, 0.42, 0.45, and 0.31 respectively, with performance improving incrementally for the mean of more measures. Correlation between the mean of 2 Oxford WebQs and estimated true intakes, reflecting attenuation when intake is categorised or ranked, was 0.47, 0.39, 0.40, and 0.38 respectively, also improving with repeated administration. These were similar to the more administratively burdensome interviewer-based recall. Using objective biomarkers as the standard, Oxford WebQ performs well across key nutrients in comparison with more administratively burdensome interviewer-based 24-hour recalls. Attenuation improves when the average is taken over repeated administration, reducing measurement error bias in assessment of diet-disease associations.

Journal article

Auvinen A, Feychting M, Ahlbom A, Hillert L, Elliott P, Schuz J, Kromhout H, Toledano MB, Johansen C, Poulsen AH, Vermeulen R, Heinavaara S, Kojo K, Tettamanti G, COSMOS Study Groupet al., 2019, Headache, tinnitus and hearing loss in the international Cohort Study of Mobile Phone Use and Health (COSMOS) in Sweden and Finland, International Journal of Epidemiology, Vol: 48, Pages: 1567-1579, ISSN: 1464-3685

BackgroundMobile phone use and exposure to radiofrequency electromagnetic fields (RF-EMF) from it have been associated with symptoms in some studies, but the studies have shortcomings and their findings are inconsistent. We conducted a prospective cohort study to assess the association between amount of mobile phone use at baseline and frequency of headache, tinnitus or hearing loss at 4-year follow-up.MethodsThe participants had mobile phone subscriptions with major mobile phone network operators in Sweden (n = 21 049) and Finland (n = 3120), gave consent for obtaining their mobile phone call data from operator records at baseline, and filled in both baseline and follow-up questionnaires on symptoms, potential confounders and further characteristics of their mobile phone use.ResultsThe participants with the highest decile of recorded call-time (average call-time >276 min per week) at baseline showed a weak, suggestive increased frequency of weekly headaches at 4-year follow-up (adjusted odds ratio 1.13, 95% confidence interval 0.95–1.34). There was no obvious gradient of weekly headache with increasing call-time (P trend 0.06). The association of headache with call-time was stronger for the Universal Mobile Telecommunications System (UMTS) network than older Global System for Mobile Telecommunications (GSM) technology, despite the latter involving higher exposure to RF-EMF. Tinnitus and hearing loss showed no association with call-time.ConclusionsPeople using mobile phones most extensively for making or receiving calls at baseline reported weekly headaches slightly more frequently at follow-up than other users, but this finding largely disappeared after adjustment for confounders and was not related to call-time in GSM with higher RF-EMF exposure. Tinnitus and hearing loss were not associated with amount of call-time.

Journal article

Iwahori T, Miura K, Ueshima H, Tanaka-Mizuno S, Chan Q, Arima H, Dyer AR, Elliott P, Stamler J, INTERSALT Research Groupet al., 2019, Urinary sodium-to-potassium ratio and intake of sodium and potassium among men and women from multiethnic general populations: the INTERSALT Study, Hypertension Research, Vol: 42, Pages: 1590-1598, ISSN: 0916-9636

The Na/K ratio may be more strongly related to blood pressure and cardiovascular disease than sodium or potassium. The casual urine Na/K ratio can provide prompt on-site feedback, and with repeated measurements, may provide useful individual estimates of the 24-h ratio. The World Health Organization has published guidelines for sodium and potassium intake, but no generally accepted guideline prevails for the Na/K ratio. We used standardized data on 24 h and casual urinary electrolyte excretion obtained from the INTERSALT Study for 10,065 individuals aged 20-59 years from 32 countries (52 populations). Associations between the casual urinary Na/K ratio and the 24-h sodium and potassium excretion of individuals were assessed by correlation and stratification analyses. The mean 24-h sodium and potassium excretions were 156.0 mmol/24 h and 55.2 mmol/24 h, respectively; the mean 24-h urinary Na/K molar ratio was 3.24. Pearson's correlation coefficients (r) for the casual urinary Na/K ratio with 24-h sodium and potassium excretions were 0.42 and -0.34, respectively, and these were 0.57 and -0.48 for the 24-h ratio. The urinary Na/K ratio predicted a 24-h urine Na excretion of <85 mmol/day (the WHO recommended guidelines) with a sensitivity of 99.7% and 94.0%, specificity of 39.5% and 48.0%, and positive predictive value of 96.3% and 61.1% at the cutoff point of 1 in 24 h and casual urine Na/K ratios, respectively. A urinary Na/K molar ratio <1 may be a useful indicator for adherence to the WHO recommended levels of sodium and, to a lesser extent, the potassium intake across different populations; however, cutoff points for Na/K ratio may be tuned for localization.

Journal article

Eriksen R, Gibson R, Aresu M, Heard A, Chan Q, Evangelou E, Gao H, Elliott P, Frost Get al., 2019, Gene-diet quality interactions on HbA1c and type 2 diabetes risk: The Airwave Health Monitoring Study, Endocrinology, Diabetes & Metabolism, Vol: 2, Pages: 1-7, ISSN: 2398-9238

Introduction: Type 2 Diabetes (T2D) is multi-factorial involving lifestyle, environmental and genetic risk factors. This study aims to investigate the impact of genetic interactions with alcohol and diet quality on glycated haemoglobin A1c (HbA1c) independent of obesity, in a British population.Methods: Cross-sectional study of 14,089 white British participants from Airwave Health Monitoring Study, and a sub-sample of 3,733 participants with dietary data. A T2D genetic risk score (GRS) was constructed and its interactions with diet on HbA1c were assessed.Results: GRS was associated with a higher HbA1c% ( 0.03, p<0.0001) and a higher risk of pre-diabetes (OR 1.09, p<0.0001) and T2D (OR 1.14, p 0.006). The genetic effect on HbA1c% was significantly higher in obese participants ( 1.88, pinteraction 0.03). A high intake of wholegrain attenuated the effect on HbA1c% in high-risk individuals pinteraction 0.04. Conclusion: The genetic effect on HbA1c was almost doubled in obese individuals, compared with those with a healthy weight, and independent of weight there was a modest offset on HbA1c in high-genetic risk individuals consuming a diet high in wholegrain. This supports the importance of a healthy diet high in wholegrains and along with maintaining a healthy weight in controlling HbA1c amongst high genetic risk groups.

Journal article

Hansell A, Cai Y, Granell R, Blangiardo M, Fecht D, Gulliver J, Henderson J, Elliott Pet al., 2019, Prenatal, early-life and childhood exposure to air pollution and lung function in the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Seow WJ, Shu X, Nicholson J, Holmes E, Walker DI, Hu W, Cai Q, Gao Y-T, Xiang Y-B, Moore S, Bassig BA, Wong JYY, Zhang J, Ji B-T, Boulange C, Kaluarachchi M, Wijeyesekera A, Zheng W, Elliott P, Rothman N, Lan Qet al., 2019, Association of untargeted urinary metabolomics and lung cancer risk among never-smoking women in China., JAMA Network Open, Vol: 2, ISSN: 2574-3805

Importance Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood.Objective To assess the association between metabolomics and lung cancer risk among never-smoking women.Design, Setting, and Participants This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women’s Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018.Exposures Untargeted ultra-high-performance liquid chromatography–tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured.Main Outcomes and Measures Incident lung cancer.Results Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odd

Journal article

Tzoulaki I, Castagné R, Boulangé CL, Karaman I, Chekmeneva E, Evangelou E, Ebbels TMD, Kaluarachchi MR, Chadeau-Hyam M, Mosen D, Dehghan A, Moayyeri A, Ferreira DLS, Guo X, Rotter JI, Taylor KD, Kavousi M, De Vries PS, Lehne B, Loh M, Hofman A, Nicholson JK, Chambers J, Gieger C, Holmes E, Tracy R, Kooner J, Greenland P, Franco OH, Herrington D, Lindon JC, Elliott Pet al., 2019, Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease, European Heart Journal, Vol: 40, Pages: 2883-2896, ISSN: 1522-9645

Aims: To characterise serum metabolic signatures associated with atherosclerosis in the coronary or carotid arteries and subsequently their association with incident cardiovascular disease (CVD). Methods and Results: We used untargeted one-dimensional (1D) serum metabolic profiling by proton (1H) nuclear magnetic resonance (NMR) spectroscopy among 3,867 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), with replication among 3,569 participants from the Rotterdam and LOLIPOP Studies. Atherosclerosis was assessed by coronary artery calcium (CAC) and carotid intima-media thickness (IMT). We used multivariable linear regression to evaluate associations between NMR features and atherosclerosis accounting for multiplicity of comparisons. We then examined associations between metabolites associated with atherosclerosis and incident CVD available in MESA and Rotterdam and explored molecular networks through bioinformatics analyses. Overall, 30 NMR measured metabolites were associated with CAC and/or IMT, P =1.3x10-14 to 6.5x10-6 (discovery), P =4.2x10-14 to 4.4x10-2 (replication). These associations were substantially attenuated after adjustment for conventional cardiovascular risk factors. Metabolites associated with atherosclerosis revealed disturbances in lipid and carbohydrate metabolism, branched-chain and aromatic amino acid metabolism, as well as oxidative stress and inflammatory pathways. Analyses of incident CVD events showed inverse associations with creatine, creatinine and phenylalanine, and direct associations with mannose, acetaminophen-glucuronide and lactate as well as apolipoprotein B (P <0.05). Conclusion: Metabolites associated with atherosclerosis were largely consistent between the two vascular beds (coronary and carotid arteries) and predominantly tag pathways that overlap with the known cardiovascular risk factors. We present an integrated systems network that highlights a series of inter-connected pathways underlying atherosclero

Journal article

Alves AC, De Silva NMG, Karhunen V, Sovio U, Das S, Rob Taal H, Warrington NM, Lewin AM, Kaakinen M, Cousminer DL, Thiering E, Timpson NJ, Bond TA, Lowry E, Brown CD, Estivill X, Lindi V, Bradfield JP, Geller F, Speed D, Coin LJM, Loh M, Barton SJ, Beilin LJ, Bisgaard H, Bønnelykke K, Alili R, Hatoum IJ, Schramm K, Cartwright R, Charles MA, Salerno V, Clément K, Claringbould AAJ, Van Duijn CM, Moltchanova E, Eriksson JG, Elks C, Feenstra B, Flexeder C, Franks S, Frayling TM, Freathy RM, Elliott P, Widén E, Hakonarson H, Hattersley AT, Rodriguez A, Banterle M, Heinrich J, Heude B, Holloway JW, Hofman A, Hyppönen E, Inskip H, Kaplan LM, Hedman AK, Läärä E, Prokisch H, Grallert H, Lakka TA, Lawlor DA, Melbye M, Ahluwalia TS, Marinelli M, Millwood IY, Palmer LJ, Pennell CE, Perry JR, Ring SM, Savolainen MJ, Rivadeneira F, Standl M, Sunyer J, Tiesler CMT, Uitterlinden AG, Schierding W, Sullivan OM, Prokopenko I, Herzig KH, Smith GD, O'Reilly P, Felix JF, Buxton JL, Blakemore AIF, Ong KK, Jaddoe VWV, Grant SFA, Sebert S, McCarthy MI, Järvelin MRet al., 2019, GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI, Science Advances, Vol: 5, ISSN: 2375-2548

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here we combine genome-wide association studies with modelling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score and co-localization analyses to determine how developmental timings, molecular pathways and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult BMI, with variants associated with adult BMI acting as early as 4-6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Journal article

Evangelou E, Gao H, Blakeley P, Pazoki R, Suzuki H, Elliott J, Karaman I, Jarvelin MR, Tzoulaki I, Bell JD, Matthews PM, Elliott Pet al., 2019, New alcohol-related genes suggest shared genetic mechanisms with neuropsychiatric disorders, Nature Human Behaviour, Vol: 3, Pages: 950-961, ISSN: 2397-3374

Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. Here we conducted a meta-analysis of genome-wide association studies of alcohol consumption (g d−1) from the UK Biobank, the Alcohol Genome-Wide Consortium and the Cohorts for Heart and Aging Research in Genomic Epidemiology Plus consortia, collecting data from 480,842 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 new common loci and investigated their potential functional importance using magnetic resonance imaging data and gene expression studies. We identify genetic pathways associated with alcohol consumption and suggest genetic mechanisms that are shared with neuropsychiatric disorders such as schizophrenia.

Journal article

Pazoki R, Evangelou E, Mosen-Ansorena D, Pinto R, Karaman I, Blakeley P, Gill D, Zuber V, Elliott P, Tzoulaki I, Dehghan Aet al., 2019, GWAS for urinary sodium and potassium excretion highlights pathways shared with cardiovascular traits, Nature Communications, Vol: 10, ISSN: 2041-1723

Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we identify 51 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits.

Journal article

Gibson R, Eriksen R, Chambers E, Gao H, Aresu M, Heard A, Chan Q, Elliott P, Frost Get 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.

Journal article

Sung YJ, de Las Fuentes L, Winkler TW, Chasman DI, Bentley AR, Kraja AT, Ntalla I, Warren HR, Guo X, Schwander K, Manning AK, Brown MR, Aschard H, Feitosa MF, Franceschini N, Lu Y, Cheng C-Y, Sim X, Vojinovic D, Marten J, Musani SK, Kilpeläinen TO, Richard MA, Aslibekyan S, Bartz TM, Dorajoo R, Li C, Liu Y, Rankinen T, Smith AV, Tajuddin SM, Tayo BO, Zhao W, Zhou Y, Matoba N, Sofer T, Alver M, Amini M, Boissel M, Chai JF, Chen X, Divers J, Gandin I, Gao C, Giulianini F, Goel A, Harris SE, Hartwig FP, He M, Horimoto ARVR, Hsu F-C, Jackson AU, Kammerer CM, Kasturiratne A, Komulainen P, Kühnel B, Leander K, Lee W-J, Lin K-H, Luan J, Lyytikäinen L-P, McKenzie CA, Nelson CP, Noordam R, Scott RA, Sheu WHH, Stančáková A, Takeuchi F, van der Most PJ, Varga TV, Waken RJ, Wang H, Wang Y, Ware EB, Weiss S, Wen W, Yanek LR, Zhang W, Zhao JH, Afaq S, Alfred T, Amin N, Arking DE, Aung T, Barr RG, Bielak LF, Boerwinkle E, Bottinger EP, Braund PS, Brody JA, Broeckel U, Cade B, Campbell A, Canouil M, Chakravarti A, Cocca M, Collins FS, Connell JM, de Mutsert R, de Silva HJ, Dörr M, Duan Q, Eaton CB, Ehret G, Evangelou E, Faul JD, Forouhi NG, Franco OH, Friedlander Y, Gao H, Gigante B, Gu CC, Gupta P, Hagenaars SP, Harris TB, He J, Heikkinen S, Heng C-K, Hofman A, Howard BV, Hunt SC, Irvin MR, Jia Y, Katsuya T, Kaufman J, Kerrison ND, Khor CC, Koh W-P, Koistinen HA, Kooperberg CB, Krieger JE, Kubo M, Kutalik Z, Kuusisto J, Lakka TA, Langefeld CD, Langenberg C, Launer LJ, Lee JH, Lehne B, Levy D, Lewis CE, Li Y, Lifelines Cohort Study, Lim SH, Liu C-T, Liu J, Liu J, Liu Y, Loh M, Lohman KK, Louie T, Mägi R, Matsuda K, Meitinger T, Metspalu A, Milani L, Momozawa Y, Mosley TH, Nalls MA, Nasri U, O'Connell JR, Ogunniyi A, Palmas WR, Palmer ND, Pankow JS, Pedersen NL, Peters A, Peyser PA, Polasek O, Porteous D, Raitakari OT, Renström F, Rice TK, Ridker PM, Robino A, Robinson JG, Rose LM, Rudan I, Sabanayagam C, Salako BL, Sandow K, Schmidt CO, Schreiner PJ, Scott WR, Sever P, Sims M, Sitet 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.

Journal article

Gill D, Georgakis MK, Koskeridis F, Jiang L, Wei WQ, Theodoratou E, Elliott P, Denny JC, Malik R, Evangelou E, Dehghan A, Dichgans M, Tzoulaki Iet 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

Journal article

Karimi M, Castagne R, Delpierre C, Albertus G, Berger E, Vineis P, Kumari M, Kelly-Irving M, Chadeau Met 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.

Journal article

Malik R, Chauhan G, Traylor M, Sargurupremraj M, Okada Y, Mishra A, Rutten-Jacobs L, Giese A-K, van der Laan SW, Gretarsdottir S, Anderson CD, Chong M, Adams HHH, Ago T, Almgren P, Amouyel P, Ay H, Bartz TM, Benavente OR, Bevan S, Boncoraglio GB, Brown RD, Butterworth AS, Carrera C, Carty CL, Chasman DI, Chen W-M, Cole JW, Correa A, Cotlarciuc I, Cruchaga C, Danesh J, de Bakker PIW, DeStefano AL, den Hoed M, Duan Q, Engelter ST, Falcone GJ, Gottesman RF, Grewal RP, Gudnason V, Gustafsson S, Haessler J, Harris TB, Hassan A, Havulinna AS, Heckbert SR, Holliday EG, Howard G, Hsu F-C, Hyacinth IH, Ikram MA, Ingelsson E, Irvin MR, Jian X, Jimenez-Conde J, Johnson JA, Jukema JW, Kanai M, Keene KL, Kissela BM, Kleindorfer DO, Kooperberg C, Kubo M, Lange LA, Langefeld CD, Langenberg C, Launer LJ, Lee J-M, Lemmens R, Leys D, Lewis CM, Lin W-Y, Lindgren AG, Lorentzen E, Magnusson PK, Maguire J, Manichaikul A, McArdle PF, Meschia JF, Mitchell BD, Mosley TH, Nalls MA, Ninomiya T, O'Donnell MJ, Psaty BM, Pulit SL, Rannikmae K, Reiner AP, Rexrode KM, Rice K, Rich SS, Ridker PM, Rost NS, Rothwell PM, Rotter JI, Rundek T, Sacco RL, Sakaue S, Sale MM, Salomaa V, Sapkota BR, Schmidt R, Schmidt CO, Schminke U, Sharma P, Slowik A, Sudlow CLM, Tanislav C, Tatlisumak T, Taylor KD, Thijs VNS, Thorleifsson G, Thorsteinsdottir U, Tiedt S, Trompet S, Tzourio C, van Duijn CM, Walters M, Wareham NJ, Wassertheil-Smoller S, Wilson JG, Wiggins KL, Yang Q, Yusuf S, Bis JC, Pastinen T, Ruusalepp A, Schadt EE, Koplev S, Bjorkegren JLM, Codoni V, Civelek M, Smith NL, Tregouet DA, Christophersen IE, Roselli C, Lubitz SA, Ellinor PT, Tai ES, Kooner JS, Kato N, He J, van der Harst P, Elliott P, Chambers JC, Takeuchi F, Johnson AD, Sanghera DK, Melander O, Jern C, Strbian D, Fernandez-Cadenas I, Longstreth WT, Rolfs A, Hata J, Woo D, Rosand J, Pare G, Hopewell JC, Saleheen D, Stefansson K, Worrall BB, Kittner SJ, Seshadri S, Fornage M, Markus HS, Howson JMM, Kamatani Y, Debette S, Dichgans Met 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

Journal article

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