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

594 results found

Robinson O, Determinants of accelerated metabolomic and epigenetic ageing in a UK cohort, Aging Cell, ISSN: 1474-9718

Journal article

Piel F, Fecht D, Hodgson S, Blangiardo M, Toledano M, Hansell A, Elliott Pet al., Small-area methods for investigation of environment and health, International Journal of Epidemiology, ISSN: 1464-3685

Small-area studies offer a powerful epidemiological approach to study disease patterns at the population level and assess health risks posed by environmental pollutants. They involve a public health investigation on a geographic scale (e.g. neighbourhood) with overlay of health, environmental, demographic and potential confounder data. Recent methodological advances, including Bayesian approaches, combined with fast growing computational capabilities permit more informative analyses than previously possible, including the incorporation of data at different scales, from satellites to individual-level survey information. Better data availability has widened the scope and utility of small-area studies, but also led to greater complexity, including choice of optimal study area size and extent, duration of study periods, range of covariates and confounders to be considered, and dealing with uncertainty. The availability of data from large, well-phenotyped cohorts such as UK Biobank enables the use of mixed-level study designs and the triangulation of evidence on environmental risks from small-area and individual-level studies, therefore improving causal inference, including use of linked biomarker and -omics data. As a result, there are now improved opportunities to investigate the impacts of environmental risk factors on human health, particularly for the surveillance and prevention of non-communicable diseases.

Journal article

Okuda N, Okayama A, Miura K, Yoshita K, Miyagawa N, Saitoh S, Nakagawa H, Sakata K, Chan Q, Elliott P, Ueshima H, Stamler Jet al., 2020, Food Sources of Dietary Potassium in the Adult Japanese Population: The International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP)., Nutrients, Vol: 12

A lower-than-recommended potassium intake is a well-established risk factor for increased blood pressure. Although the Japanese diet is associated with higher sodium intake and lower potassium intake, few studies have examined the source foods quantitatively. Studies on dietary patterns in association with potassium intake will be useful to provide dietary advice to increase potassium intake. Twenty-four-hour (hr) dietary recall data and 24-hr urinary potassium excretion data from Japanese participants (574 men and 571 women) in the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were used to calculate food sources of potassium and compare food consumption patterns among quartiles of participants categorized according to 24-hr urinary potassium excretion per unit of body weight (UK/BW). The average potassium intake was 2791 mg/day per participant, and the major sources were vegetables and fruits (1262 mg/day), fish (333 mg/day), coffee and tea (206 mg/day), and milk and dairy products (200 mg/day). Participants in the higher UK/BW quartile consumed significantly more vegetables and fruits, fish, and milk and dairy products, and ate less rice and noodles. Conclusion: Advice to increase the intake of vegetables and fruits, fish, and milk may be useful to increase potassium intake in Japan.

Journal article

Zhang Y, Elliott P, Toledano M, Schumann Get al., The Consortium on Vulnerability to Externalising Disorders and Addictions (c-VEDA): an accelerated longitudinal cohort of children and adolescents in India, Molecular Psychiatry, ISSN: 1359-4184

The global burden of disease attributable to externalising disorders such as alcohol misusecalls urgently for effective prevention and intervention. As our current knowledge is mainlyderived from high-income countries such in Europe and North-America, it is difficult toaddress the wider socio-cultural, psychosocial context, and genetic factors in which risk andresilience are embedded in low- and medium-income countries. c-VEDA was established asthe first and largest India-based multi-site cohort investigating the vulnerabilities for thedevelopment of externalising disorders, addictions, and other mental health problems. Usinga harmonised data collection plan coordinated with multiple cohorts in China, USA, andEurope, baseline data were collected from 7 study sites between November 2016 and May2019. 9010 participants between the ages of 6 and 23 were assessed during this time, amongstwhich 1278 participants underwent more intensive assessments including MRI scans. Bothwaves of follow-ups have started according to the accelerated cohort structure with plannedmissingness design. Here we present descriptive statistics on several key domains ofassessments, and the full baseline dataset will be made accessible for researchers outside theconsortium in September 2019. More details can be found on our website [cveda.org].

Journal article

Cai Y, Hansell AL, Granell R, Blangiardo M, Zottoli M, Fecht D, Gulliver J, Henderson AJ, Elliott Pet al., 2020, Prenatal, early-life and childhood exposure to air pollution and lung function: the ALSPAC cohort., American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X

RATIONALE: Exposure to air pollution during intrauterine development and through childhood may have lasting effects on respiratory health. OBJECTIVES: To investigate lung function at ages 8 and 15 years in relation to air pollution exposures during pregnancy, infancy and childhood in a UK population-based birth cohort. METHODS: Individual exposures to source-specific particulate matter with diameter ≤10µm (PM10) during each trimester, 0-6 months, 7-12 months (1990-1993) and up to age 15 years (1991-2008) were examined in relation to %predicted Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at ages 8(N=5,276) and 15(N=3,446) years, usinglinear regression models adjusted for potential confounders. A profile regression model was used to identify sensitive time periods. MEASUREMENTS AND MAIN RESULTS: We did not find clear evidence for a sensitive exposure period for PM10 from road-traffic: at age 8 years, 1µg/m3 higher exposure during the first trimester was associated with lower %predicted of FEV1(-0.826, 95%CI:-1.357 to -0.296) and FVC(-0.817, 95%CI:-1.357 to -0.276), but similar associations were seen for exposures for other trimesters, 0-6 months, 7-12 months, and 0-7 years. Associations were stronger among boys, children whose mother had a lower education level or smoked during pregnancy. For PM10 from all sources, the third trimester was associated with lower %predicted of FVC (-1.312, 95%CI: -2.100 to -0.525). At age 15 years, no adverse associations were seen with lung function. CONCLUSIONS: Exposure to road-traffic PM10 during pregnancy may result in small but significant reductions in lung function at age 8 years.

Journal article

Huang L, Tian M, Yu J, Li Q, Liu Y, Yin X, Wu JH, Marklund M, Wu Y, Li N, Elliott P, Yan LL, Labarthe DR, Hao Z, Shi J, Feng X, Zhang J, Zhang Y, Zhang R, Zhou B, Li Z, Sun J, Zhao Y, Yu Y, Neal Bet al., 2020, Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS), American Heart Journal, Vol: 221, Pages: 136-145, ISSN: 0002-8703

The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.

Journal article

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

Sheehan A, Freni Sterrantino A, Fecht D, Elliott P, Hodgson Set al., 2020, Childhood Type 1 diabetes: an environment wide association study across England, Diabetologia, ISSN: 0012-186X

Aims:Type 1 Diabetes is an autoimmune disease affecting ~400,000 people across the UK. Environmental factors likely trigger the disease processin genetically susceptible individuals. We assessed the associations between a wide range of environmental factors and childhood type 1 diabetesincidence in England, using an agnostic, ecological Environment Wide Association Study (EnWAS) approach, to generate hypotheses about environmental triggers. Methods:We undertook analyses at the Local Authority District (LAD) level using a national Hospital Episode Statistics (HES) based incident type 1 diabetesdataset, comprising 13,948 cases aged 0-9 years over the period April 2000-March 2011. We compiled LAD-level estimates for a range of potential demographic and environmental risk factors including meteorological, land use and environmental pollution variables. The associations between type 1 diabetesincidence and risk factors were assessed via Poisson regression, disease mapping and ecological regression. 8Results:Case counts by LAD varied from 1 to 236(median 33;inter quartile range: 24-46). Overall type 1 diabetesincidence was 21.2 (95% CI 20.9-21.6) per 100,000individuals. The EnWASand disease mapping indicated that 15out of 53 demographic and environmental risk factors were significantly associated with diabetes incidence after adjusting for multiple testing.These included air pollutants (particulate matter, nitrogen dioxide, nitrogen oxides, carbon monoxide, all inversely associated), as well as lead in soil, radon, outdoor light at night, overcrowding, population density and ethnicity. Disease mapping revealed spatial heterogeneity in type 1 diabetesrisk. The ecological regression found anassociationbetween type 1 diabetesand thelivingenvironmentdomainof the Index of Multiple Deprivation(RR 0.995 (95%Credible Interval (CrI)0.991-0.998))and radon potential class (RR 1.044 95%CrI 1.015-1.074). Conclusions:Our analysis identifiesa range of demographic and environmental facto

Journal article

Georgakis MK, Gill D, Webb AJS, Evangelou E, Elliott P, Sudlow CLM, Dehghan A, Malik R, Tzoulaki I, Dichgans Met al., Genetically determined blood pressure, antihypertensive drug classes and risk of stroke subtypes, Neurology, ISSN: 0028-3878

Objective: We employed Mendelian Randomization to explore whether the effects of blood pressure (BP) and BP lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology. Methods: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from a GWAS on 757,601 individuals. Applying two-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of WMH.Results: Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not beta blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for CCBs showed particularly strong associations with small vessel stroke and the related radiological phenotype of WMH.Conclusions: This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.

Journal article

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

Parkes B, Hansell AL, Ghosh R, Douglas P, Fecht D, Wellesley D, Kurinczuk JJ, Rankin J, de Hoogh C, 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, Environment International, Vol: 134, ISSN: 0160-4120

BackgroundFew studies have investigated congenital anomalies in relation to municipal waste incinerators (MWIs) and results are inconclusive.ObjectivesTo 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.MethodsRetrospective 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.ResultsAnalysis 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.DiscussionWe 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

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

Toledano MB, Shaddick G, de Hoogh C, Fecht D, Freni Sterrantino A, Matthews J, Wright M, Gulliver J, Elliott Pet al., Electric field and air ion exposures near high voltage overhead power lines and adult cancers: a case control study across England and Wales, International Journal of Epidemiology, ISSN: 0300-5771

Background: Various mechanisms have been postulated to explain how electric fields emitted by high voltage overhead power lines, and the charged ions they produce, might be associated with possible adult cancer risk but this has not previously been systematically explored in large scale epidemiologic research. Methods: We investigated risks of adult cancers in relation to modelled air ion density (per cm3) within 600m (focusing analysis on mouth, lung, respiratory) and calculated electric field within 25m (focusing analysis on non-melanoma skin) of high voltage overhead power lines in England and Wales, 1974-2008. Results: With adjustment for age, sex, deprivation and rurality, odds ratios (OR) in the highest fifth of net air ion density (0.504-1) compared with the lowest (0-0.1879) ranged from 0.94 (95% CI 0.82 – 1.08) for mouth cancers to 1.03 (95% CI 0.97 -1.09) for respiratory system cancers, with no trends in risk. The pattern of cancer risk was similar using corona ion estimates from an alternative model proposed by others. For keratinocyte carcinoma, adjusted OR in the highest (1.06 - 4.11 kV/m) compared with the lowest (<0.70 kV/m) thirds of electric field strength was 1.23 (95% CI 0.65-2.34) with no trend in risk. Conclusions: Our results do not provide evidence to support hypotheses that air ion density or electric fields in the vicinity of power lines are associated with cancer risk in adults.

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, 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

<ns5:p><ns5:bold>Background:</ns5: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.</ns5:p><ns5:p> <ns5:bold>Methods:</ns5: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.</ns5:p><ns5:p> <ns5:bold>Discussion:</ns5: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., 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

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

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

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

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