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

605 results found

Bentham J, Di Cesare M, Stevens GA, Zhou B, Bixby H, Cowan M, Fortunato L, Bennett J, Danaei G, Hajifathalian K, Lu Y, Riley LM, Laxmaiah A, Kontis V, Paciorek CJ, Riboli E, Ezzati M, Chan Q, Elliott P, Gunter M, Hihtaniemi IT, Murphy N, Norat T, Riboli E, Vineis P, NCD Risk Factor Collaboration NCD-RisCet al., 2016, A century of trends in adult human height, eLife, Vol: 5, ISSN: 2050-084X

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

Journal article

Elliott P, Burgess AP, fouquet NC, Seri S, Hawken MB, Heard A, Neasham D, Little MPet al., 2016, Acute Exposure to Terrestrial Trunked Radio (TETRA) has effects on theelectroencephalogram and electrocardiogram, consistent with vagal nervestimulation., Environmental Research, Vol: 150, Pages: 461-469, ISSN: 1096-0953

BackgroundTerrestrial Trunked Radio (TETRA) is a telecommunications system widely used by police and emergency services around the world. The Stewart Report on mobile telephony and health raised questions about possible health effects associated with TETRA signals. This study investigates possible effects of TETRA signals on the electroencephalogram and electrocardiogram in human volunteers.MethodsBlinded randomized provocation study with a standardized TETRA signal or sham exposure. In the first of two experiments, police officers had a TETRA set placed first against the left temple and then the upper-left quadrant of the chest and the electroencephalogram was recorded during rest and active cognitive processing. In the second experiment, volunteers were subject to chest exposure of TETRA whilst their electroencephalogram and heart rate variability derived from the electrocardiogram were recorded.ResultsIn the first experiment, we found that exposure to TETRA had consistent neurophysiological effects on the electroencephalogram, but only during chest exposure, in a pattern suggestive of vagal nerve stimulation. In the second experiment, we observed changes in heart rate variability during exposure to TETRA but the electroencephalogram effects were not replicated.ConclusionsObserved effects of exposure to TETRA signals on the electroencephalogram (first experiment) and electrocardiogram are consistent with vagal nerve stimulation in the chest by TETRA. However given the small effect on heart rate variability and the lack of consistency on the electroencephalogram, it seems unlikely that this will have a significant impact on health. Long-term monitoring of the health of the police force in relation to TETRA use is on-going.

Journal article

Bakolis I, Kelly R, Fecht D, Best N, Millett C, Garwood K, Elliott P, Hansell A, Hodgson Set al., 2016, Protective Effects of Smoke-free Legislation on Birth Outcomes in England: A Regression Discontinuity Design, Epidemiology, Vol: 27, Pages: 810-818, ISSN: 1531-5487

Background: Environmental tobacco smoke has an adverse impact on preterm birth and birthweight. England introduced a new law to make virtually all enclosed public places andworkplaces smoke free on July 1 2007. We investigated the effect of smoke-free legislation onbirth outcomes in England using Hospital Episode Statistics (HES) maternity data.Methods: We used regression discontinuity, a quasi-experimental study design, which canfacilitate valid causal inference, to analyse short-term effects of smoke-free legislation on birthweight, low birth weight, gestational age, preterm birth and small for gestational age.Results: We analysed 1,800,906 pregnancies resulting in singleton live-births in Englandbetween January 1 2005 and December 31 2009. In the one to five months following theintroduction of the smoking-free legislation, for those entering their third trimester, the risk oflow birth weight decreased by between 8% (95% CI: 4%-12%) and 14% (95% CI: 5%-23%),very low birth weight between 28% (95% CI: 19%-36%) and 32% (95% CI: 21%-41%), pretermbirth between 4% (95% CI: 1%-8%) and 9% (95% CI: 2%-16%), and small for gestational agebetween 5% (95% CI: 2%-8%) and 9% (95% CI: 2%-15%). The impact of the smoke-freelegislation varied by maternal age, deprivation, ethnicity and region.Conclusions: The introduction of smoke-free legislation in England had an immediate beneficialimpact on birth outcomes overall, although this benefit was not observed across all age, ethnic, ordeprivation groups.

Journal article

Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, Ma C, Fontanillas P, Moutsianas L, McCarthy DJ, Rivas MA, Perry JR, Sim X, Blackwell TW, Robertson NR, Rayner NW, Cingolani P, Locke AE, Tajes JF, Highland HM, Dupuis J, Chines PS, Lindgren CM, Hartl C, Jackson AU, Chen H, Huyghe JR, van de Bunt M, Pearson RD, Kumar A, Müller-Nurasyid M, Grarup N, Stringham HM, Gamazon ER, Lee J, Chen Y, Scott RA, Below JE, Chen P, Huang J, Go MJ, Stitzel ML, Pasko D, Parker SC, Varga TV, Green T, Beer NL, Day-Williams AG, Ferreira T, Fingerlin T, Horikoshi M, Hu C, Huh I, Ikram MK, Kim BJ, Kim Y, Kim YJ, Kwon MS, Lee J, Lee S, Lin KH, Maxwell TJ, Nagai Y, Wang X, Welch RP, Yoon J, Zhang W, Barzilai N, Voight BF, Han BG, Jenkinson CP, Kuulasmaa T, Kuusisto J, Manning A, Ng MC, Palmer ND, Balkau B, Stančáková A, Abboud HE, Boeing H, Giedraitis V, Prabhakaran D, Gottesman O, Scott J, Carey J, Kwan P, Grant G, Smith JD, Neale BM, Purcell S, Butterworth AS, Howson JM, Lee HM, Lu Y, Kwak SH, Zhao W, Danesh J, Lam VK, Park KS, Saleheen D, So WY, Tam CH, Afzal U, Aguilar D, Arya R, Aung T, Chan E, Navarro C, Cheng CY, Palli D, Correa A, Curran JE, Rybin D, Farook VS, Fowler SP, Freedman BI, Griswold M, Hale DE, Hicks PJ, Khor CC, Kumar S, Lehne B, Thuillier D, Lim WY, Liu J, van der Schouw YT, Loh M, Musani SK, Puppala S, Scott WR, Yengo L, Tan ST, Taylor HA, Thameem F, Wilson G, Wong TY, Njølstad PR, Levy JC, Mangino M, Bonnycastle LL, Schwarzmayr T, Fadista J, Surdulescu GL, Herder C, Groves CJ, Wieland T, Bork-Jensen J, Brandslund I, Christensen C, Koistinen HA, Doney AS, Kinnunen L, Esko T, Farmer AJ, Hakaste L, Hodgkiss D, Kravic J, Lyssenko V, Hollensted M, Jørgensen ME, Jørgensen T, Ladenvall C, Justesen JM, Käräjämäki A, Kriebel J, Rathmann W, Lannfelt L, Lauritzen T, Narisu N, Linneberg A, Melander O, Milani L, Neville M, Orho-Melander M, Qi L, Qi Q, Roden M, Rolandsson O, Swift A, Rosengren AH, Stirrups K, Wood AR, Mihailov E, Blancher C, Carneiro MO, Maget al., 2016, The genetic architecture of type 2 diabetes., Nature, Vol: 536, Pages: 41-47, ISSN: 0028-0836

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

Journal article

Chami N, Chen MH, Slater AJ, Eicher JD, Evangelou E, Tajuddin SM, Love-Gregory L, Kacprowski T, Schick UM, Nomura A, Giri A, Lessard S, Brody JA, Schurmann C, Pankratz N, Yanek LR, Manichaikul A, Pazoki R, Mihailov E, Hill WD, Raffield LM, Burt A, Bartz TM, Becker DM, Becker LC, Boerwinkle E, Bork-Jensen J, Bottinger EP, O'Donoghue ML, Crosslin DR, de Denus S, Dubé MP, Elliott P, Engström G, Evans MK, Floyd JS, Fornage M, Gao H, Greinacher A, Gudnason V, Hansen T, Harris TB, Hayward C, Hernesniemi J, Highland HM, Hirschhorn JN, Hofman A, Irvin MR, Kähönen M, Lange E, Launer LJ, Lehtimäki T, Li J, Liewald DC, Linneberg A, Liu Y, Lu Y, Lyytikäinen LP, Mägi R, Mathias RA, Melander O, Metspalu A, Mononen N, Nalls MA, Nickerson DA, Nikus K, O'Donnell CJ, Orho-Melander M, Pedersen O, Petersmann A, Polfus L, Psaty BM, Raitakari OT, Raitoharju E, Richard M, Rice KM, Rivadeneira F, Rotter JI, Schmidt F, Smith AV, Starr JM, Taylor KD, Teumer A, Thuesen BH, Torstenson ES, Tracy RP, Tzoulaki I, Zakai NA, Vacchi-Suzzi C, van Duijn CM, van Rooij FJ, Cushman M, Deary IJ, Velez Edwards DR, Vergnaud AC, Wallentin L, Waterworth DM, White HD, Wilson JG, Zonderman AB, Kathiresan S, Grarup N, Esko T, Loos RJ, Lange LA, Faraday N, Abumrad NA, Edwards TL, Ganesh SK, Auer PL, Johnson AD, Reiner AP, Lettre Get al., 2016, Exome genotyping identifies pleiotropic variants associated with red blood cell traits, American Journal of Human Genetics, Vol: 99, Pages: 8-21, ISSN: 1537-6605

Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 × 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 × 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 × 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 × 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 × 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.

Journal article

Tajuddin SM, Schick UM, Eicher JD, Chami N, Giri A, Brody JA, Hill WD, Kacprowski T, Li J, Lyytikäinen LP, Manichaikul A, Mihailov E, O'Donoghue ML, Pankratz N, Pazoki R, Polfus LM, Smith AV, Schurmann C, Vacchi-Suzzi C, Waterworth DM, Evangelou E, Yanek LR, Burt A, Chen MH, van Rooij FJ, Floyd JS, Greinacher A, Harris TB, Highland HM, Lange LA, Liu Y, Mägi R, Nalls MA, Mathias RA, Nickerson DA, Nikus K, Starr JM, Tardif JC, Tzoulaki I, Velez Edwards DR, Wallentin L, Bartz TM, Becker LC, Denny JC, Raffield LM, Rioux JD, Friedrich N, Fornage M, Gao H, Hirschhorn JN, Liewald DC, Rich SS, Uitterlinden A, Bastarache L, Becker DM, Boerwinkle E, de Denus S, Bottinger EP, Hayward C, Hofman A, Homuth G, Lange E, Launer LJ, Lehtimäki T, Lu Y, Metspalu A, O'Donnell CJ, Quarells RC, Richard M, Torstenson ES, Taylor KD, Vergnaud AC, Zonderman AB, Crosslin DR, Deary IJ, Dörr M, Elliott P, Evans MK, Gudnason V, Kähönen M, Psaty BM, Rotter JI, Slater AJ, Dehghan A, White HD, Ganesh SK, Loos RJ, Esko T, Faraday N, Wilson JG, Cushman M, Johnson AD, Edwards TL, Zakai NA, Lettre G, Reiner AP, Auer PLet al., 2016, Large-scale exome-wide association analysis identifies loci for white blood cell traits and pleiotropy with immune-mediated diseases, American Journal of Human Genetics, Vol: 99, Pages: 22-39, ISSN: 1537-6605

White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3' UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases.

Journal article

Eicher JD, Chami N, Kacprowski T, Nomura A, Chen MH, Yanek LR, Tajuddin SM, Schick UM, Slater AJ, Pankratz N, Polfus L, Schurmann C, Giri A, Brody JA, Lange LA, Manichaikul A, Hill WD, Pazoki R, Elliot P, Evangelou E, Tzoulaki I, Gao H, Vergnaud AC, Mathias RA, Becker DM, Becker LC, Burt A, Crosslin DR, Lyytikäinen LP, Nikus K, Hernesniemi J, Kähönen M, Raitoharju E, Mononen N, Raitakari OT, Lehtimäki T, Cushman M, Zakai NA, Nickerson DA, Raffield LM, Quarells R, Willer CJ, Peloso GM, Abecasis GR, Liu DJ, Global Lipids Genetics Consortium, Deloukas P, Samani NJ, Schunkert H, Erdmann J, CARDIoGRAM Exome Consortium, Myocardial Infarction Genetics Consortium, Fornage M, Richard M, Tardif JC, Rioux JD, Dube MP, de Denus S, Lu Y, Bottinger EP, Loos RJ, Smith AV, Harris TB, Launer LJ, Gudnason V, Velez Edwards DR, Torstenson ES, Liu Y, Tracy RP, Rotter JI, Rich SS, Highland HM, Boerwinkle E, Li J, Lange E, Wilson JG, Mihailov E, Mägi R, Hirschhorn J, Metspalu A, Esko T, Vacchi-Suzzi C, Nalls MA, Zonderman AB, Evans MK, Engström G, Orho-Melander M, Melander O, O'Donoghue ML, Waterworth DM, Wallentin L, White HD, Floyd JS, Bartz TM, Rice KM, Psaty BM, Starr JM, Liewald DC, Hayward C, Deary IJ, Greinacher A, Völker U, Thiele T, Völzke H, van Rooij FJ, Uitterlinden AG, Franco OH, Dehghan A, Edwards TL, Ganesh SK, Kathiresan S, Faraday N, Auer PL, Reiner AP, Lettre G, Johnson ADet al., 2016, Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals, American Journal of Human Genetics, Vol: 99, Pages: 40-55, ISSN: 1537-6605

Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common (ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV (PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.

Journal article

Scheelbeek PF, Khan AE, Mojumder S, Elliott P, Vineis Pet al., 2016, Drinking Water Sodium and Elevated Blood Pressure of Healthy Pregnant Women in Salinity-Affected Coastal Areas, Hypertension, Vol: 68, Pages: 464-470, ISSN: 1524-4563

Coastal areas in Southeast Asia are experiencing high sodium concentrations in drinking water sources that are commonly consumed by local populations. Salinity problems caused by episodic cyclones and subsequent seawater inundations are likely (partly) related to climate change and further exacerbated by changes in upstream river flow and local land-use activities. Dietary (food) sodium plays an important role in the global burden of hypertensive disease. It remains unknown, however, if sodium in drinking water-rather than food-has similar effects on blood pressure and disease risk. In this study, we examined the effect of drinking water sodium on blood pressure of pregnant women: increases in blood pressure in this group could severely affect maternal and fetal health. Data on blood pressure, drinking water source, and personal, lifestyle, and environmental confounders was obtained from 701 normotensive pregnant women residing in coastal Bangladesh. Generalized linear mixed regression models were used to investigate association of systolic and diastolic blood pressure of these-otherwise healthy-women with their water source. After adjustment for confounders, drinkers of tube well and pond water (high saline sources) were found to have significantly higher average systolic (+4.85 and +3.62 mm Hg) and diastolic (+2.30 and +1.72 mm Hg) blood pressures than rainwater drinkers. Drinking water salinity problems are expected to exacerbate in the future, putting millions of coastal people-including pregnant women-at increased risk of hypertension and associated diseases. There is an urgent need to further explore the health risks associated to this understudied environmental health problem and feasibility of possible adaptation strategies.

Journal article

Tzoulaki I, Elliott P, Kontis V, Ezzati Met al., 2016, Worldwide Exposures to Cardiovascular Risk Factors and Associated Health Effects: Current Knowledge and Data Gaps, Circulation, Vol: 133, Pages: 2314-2333, ISSN: 0009-7322

Information on exposure to, and health effects of, cardiovascular disease (CVD) risk factors is needed to develop effective strategies to prevent CVD events and deaths. Here, we provide an overview of the data and evidence on worldwide exposures to CVD risk factors and the associated health effects. Global comparative risk assessment studies have estimated that hundreds of thousands or millions of CVD deaths are attributable to established CVD risk factors (high blood pressure and serum cholesterol, smoking, and high blood glucose), high body mass index, harmful alcohol use, some dietary and environmental exposures, and physical inactivity. The established risk factors plus body mass index are collectively responsible for ≈9.7 million annual CVD deaths, with high blood pressure accounting for more CVD deaths than any other risk factor. Age-standardized CVD death rates attributable to established risk factors plus high body mass index are lowest in high-income countries, followed by Latin America and the Caribbean; they are highest in the region of central and eastern Europe and central Asia. However, estimates of the health effects of CVD risk factors are highly uncertain because there are insufficient population-based data on exposure to most CVD risk factors and because the magnitudes of their effects on CVDs in observational studies are likely to be biased. We identify directions for research and surveillance to better estimate the effects of CVD risk factors and policy options for reducing CVD burden by modifying preventable risk factors.

Journal article

Nakamura Y, Ueshima H, Okuda N, Miura K, Kita Y, Miyagawa N, Yoshita K, Nakagawa H, Sakata K, Saitoh S, Okamura T, Okayama A, Choudhry SR, Rodriguez B, Masaki KH, Chan Q, Elliott P, Stamler Jet al., 2016, Relationship of three different types of low-carbohydrate diet to cardiometabolic risk factors in a Japanese population: the INTERMAP/INTERLIPID Study, EUROPEAN JOURNAL OF NUTRITION, Vol: 55, Pages: 1515-1524, ISSN: 1436-6207

Journal article

Scott WR, Zhang W, Loh M, Tan S-T, Lehne B, Afzal U, Peralta J, Saxena R, Ralhan S, Wander GS, Bozaoglu K, Sanghera DK, Elliott P, Scott J, Chambers JC, Kooner JSet al., 2016, Investigation of Genetic Variation Underlying Central Obesity amongst South Asians, PLOS One, Vol: 11, ISSN: 1932-6203

ArticleAuthorsMetricsCommentsRelated ContentAbstractIntroductionMaterials and MethodsResultsDiscussion and ConclusionSupporting InformationAcknowledgmentsAuthor ContributionsReferencesReader Comments (0)Media Coverage (0)FiguresAbstractSouth Asians are 1/4 of the world’s population and have increased susceptibility to central obesity and related cardiometabolic disease. Knowledge of genetic variants affecting risk of central obesity is largely based on genome-wide association studies of common SNPs in Europeans. To evaluate the contribution of DNA sequence variation to the higher levels of central obesity (defined as waist hip ratio adjusted for body mass index, WHR) among South Asians compared to Europeans we carried out: i) a genome-wide association analysis of >6M genetic variants in 10,318 South Asians with focused analysis of population-specific SNPs; ii) an exome-wide association analysis of ~250K SNPs in protein-coding regions in 2,637 South Asians; iii) a comparison of risk allele frequencies and effect sizes of 48 known WHR SNPs in 12,240 South Asians compared to Europeans. In genome-wide analyses, we found no novel associations between common genetic variants and WHR in South Asians at P<5x10-8; variants showing equivocal association with WHR (P<1x10-5) did not replicate at P<0.05 in an independent cohort of South Asians (N = 1,922) or in published, predominantly European meta-analysis data. In the targeted analyses of 122,391 population-specific SNPs we also found no associations with WHR in South Asians at P<0.05 after multiple testing correction. Exome-wide analyses showed no new associations between genetic variants and WHR in South Asians, either individually at P<1.5x10-6 or grouped by gene locus at P<2.5x10−6. At known WHR loci, risk allele frequencies were not higher in South Asians compared to Europeans (P = 0.77), while effect sizes were unexpectedly smaller in South Asians than Europeans (P<5.0x10-8). Our find

Journal article

Vergnaud A-C, Aresu M, McRobie D, Singh D, Spear J, Heard A, Elliott Pet al., 2016, Validation of objective records and misreporting of personal radio use in a cohort of British Police forces (the Airwave Health Monitoring Study), ENVIRONMENTAL RESEARCH, Vol: 148, Pages: 367-375, ISSN: 0013-9351

Journal article

Blaise B, Correia G, Tin A, Young J, Vergnaud A, Lewis M, Pearce J, Elliott P, Nicholson J, Holmes E, Ebbels TMDet al., 2016, A novel method for power analysis and sample size determination in metabolic phenotyping, Analytical Chemistry, Vol: 88, Pages: 5179-5188, ISSN: 1520-6882

Estimation of statistical power and sample size is a key aspect of experimental design. However, in metabolic phenotyping, there is currently no accepted approach for these tasks, in large part due to the unknown nature of the expected effect. In such hypothesis free science, neither the number or class of important analytes nor the effect size are known a priori. We introduce a new approach, based on multivariate simulation, which deals effectively with the highly correlated structure and high-dimensionality of metabolic phenotyping data. First, a large data set is simulated based on the characteristics of a pilot study investigating a given biomedical issue. An effect of a given size, corresponding either to a discrete (classification) or continuous (regression) outcome is then added. Different sample sizes are modeled by randomly selecting data sets of various sizes from the simulated data. We investigate different methods for effect detection, including univariate and multivariate techniques. Our framework allows us to investigate the complex relationship between sample size, power, and effect size for real multivariate data sets. For instance, we demonstrate for an example pilot data set that certain features achieve a power of 0.8 for a sample size of 20 samples or that a cross-validated predictivity QY2 of 0.8 is reached with an effect size of 0.2 and 200 samples. We exemplify the approach for both nuclear magnetic resonance and liquid chromatography–mass spectrometry data from humans and the model organism C. elegans.

Journal article

Lehne B, Drong AW, Loh M, Zhang W, Scott WR, Tan ST, Afzal U, Schulz R, Scott J, Jarvelin MR, Elliott P, McCarthy MI, Kooner JS, Chambers JCet al., 2016, Erratum to: A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies., Genome Biology, Vol: 17, ISSN: 1474-760X

Journal article

Scheelbeek PFD, Chowdhury MAH, Haines A, Alam A, Hoque MA, Butler AP, Khan AE, Mojumder SK, Blangiardo MAG, Elliott P, Vineis Pet al., 2016, High concentrations of sodium in drinking water and raised blood pressure in coastal deltas affected by episodic seawater inundations, Lancet Global Health, Vol: 4, ISSN: 2214-109X

Background In times of seawater inundation in coastal deltas, unprotected drinking water sources, such as ponds andshallow tube wells, take on salt water with each inundation. Daily consumption of these saline sources contributes tooverall sodium intake. Although there is evidence that a high dietary salt intake is an important risk factor forhypertension, little is known about the eff ect of high concentrations of sodium in drinking water on populationhealth. In this longitudinal study, we aimed to measure the eff ect of high concentrations of sodium in drinking wateron blood pressure and to assess the reversibility of raised blood pressure when conventional drinking water sourceswere replaced by low-saline water.Methods We used a multistage sampling process to recruit participants aged 18 years or older from the salinityaffectedsub-districts of Dacope, Batiagatha, and Paikgatchha in coastal Bangladesh. Most participants consumeddrinking water from highly saline sources, such as ponds and tube-wells, while a small percentage had access torainwater. In March, 2013, we recorded: baseline concentrations of sodium in drinking water; participants’ bloodpressure; and personal, lifestyle, and environmental characteristics. During the study period, some study participantsgained access to low-saline drinking water alternatives that were installed for use in the dry season, when water fromponds becomes more saline. In March, 2014, and May, 2014, we made follow-up assessments of drinking watersodium, blood pressure, and repeated the questionnaire about personal, lifestyle, and environmental characteristics.We used generalised linear mixed methods to model the eff ect of drinking water sodium on blood pressure andassess reversibility of raised blood pressure when participants switched from conventional drinking water sources tolow-saline alternatives.Findings We included data from 581 participants in analysis, of which 277 (48%) were male. Median age was 38 years(IQR 30&

Journal article

Di Cesare M, Bentham J, Stevens GA, Zhou B, Danaei G, Lu Y, Bixby H, Cowan MJ, Riley LM, Hajifathalian K, Fortunato L, Taddei C, Bennett JE, Ikeda N, Khang Y-H, Kyobutungi C, Laxmaiah A, Li Y, Lin H-H, Miranda JJ, Mostafa A, Turley ML, Paciorek CJ, Gunter M, Ezzati M, Abdeen ZA, Hamid ZA, Abu-Rmeileh NM, Acosta-Cazares B, Adams R, Aekplakorn W, Aguilar-Salinas CA, Ahmadvand A, Ahrens W, Ali MM, Alkerwi A, Alvarez-Pedrerol M, Aly E, Amouyel P, Amuzu A, Andersen LB, Anderssen SA, Andrade DS, Anjana RM, Aounallah-Skhiri H, Ariansen I, Aris T, Arlappa N, Arveiler D, Assah FK, Avdicova M, Azizi F, Babu BV, Balakrishna N, Bandosz P, Banegas JR, Barbagallo CM, Barcelo A, Barkat A, Barros MV, Bata I, Batieha AM, Batista RL, Baur LA, Beaglehole R, Ben Romdhane H, Benet M, Bernabe-Ortiz A, Bernotiene G, Bettiol H, Bhagyalaxmi A, Bharadwaj S, Bhargava SK, Bhatti Z, Bhutta ZA, Bi H, Bi Y, Bjerregaard P, Bjertness E, Bjertness MB, Bjorkelund C, Blake M, Blokstra A, Bo S, Bobak M, Boddy LM, Boehm BO, Boeing H, Boissonnet CP, Bongard V, Bovet P, Braeckman L, Bragt MCE, Brajkovich I, Branca F, Breckenkamp J, Brenner H, Brewster LM, Brian GR, Bruno G, Bueno-de-Mesquita HBA, Bugge A, Burns C, Cabrera de Leon A, Cacciottolo J, Cama T, Cameron C, Camolas J, Can G, Candido APC, Capuano V, Cardoso VC, Carvalho MJ, Casanueva FF, Casas J-P, Caserta CA, Castetbon K, Chamukuttan S, Chan AW, Chan Q, Chaturvedi HK, Chaturvedi N, Chen C-J, Chen F, Chen H, Chen S, Chen Z, Cheng C-Y, Chetrit A, Chiolero A, Chiou S-T, Chirita-Emandi A, Cho Y, Christensen K, Chudek J, Cifkova R, Claessens F, Clays E, Concin H, Cooper C, Cooper R, Coppinger TC, Costanzo S, Cottel D, Cowell C, Craig CL, Crujeiras AB, D'Arrigo G, d'Orsi E, Dallongeville J, Damasceno A, Damsgaard CT, Danaei G, Dankner R, Dauchet L, De Backer G, De Bacquer D, de Gaetano G, De Henauw S, De Smedt D, Deepa M, Deev AD, Dehghan A, Delisle H, Delpeuch F, Dhana K, Di Castelnuovo AF, Dias-da-Costa JS, Diaz A, Djalalinia S, Do HTP, Dobson AJ, Doet al., 2016, Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants, Lancet, Vol: 387, Pages: 1377-1396, ISSN: 1474-547X

BackgroundUnderweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries.MethodsWe analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18·5 kg/m2 [underweight], 18·5 kg/m2 to <20 kg/m2, 20 kg/m2 to <25 kg/m2, 25 kg/m2 to <30 kg/m2, 30 kg/m2 to <35 kg/m2, 35 kg/m2 to <40 kg/m2, ≥40 kg/m2 [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue.FindingsWe used 1698 population-based data sources, with more than 19·2 million adult participants (9·9 million men and 9·3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21·7 kg/m2 (95% credible interval 21·3–22·1) in 1975 to 24·2 kg/m2 (24·0–24·4) in 2014 in men, and from 22·1 kg/m2 (21·7–22·5) in 1975 to 24·4 kg/m2 (24·2–24·6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21·4 kg/m2 in central Africa and south Asia to 29·2 kg/m2 (28·6–29·8) in Polynesia and Micronesia; for women the range was from 21·8 kg/m2 (21·4–22·3) in south Asia to 32·2 kg/m2 (31·5–32·8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of un

Journal article

van Leeuwen EM, Sabo A, Bis JC, Huffman JE, Manichaikul A, Smith AV, Feitosa MF, Demissie S, Joshi PK, Duan Q, Marten J, van Klinken JB, Surakka I, Nolte IM, Zhang W, Mbarek H, Li-Gao R, Trompet S, Verweij N, Evangelou E, Lyytikäinen LP, Tayo BO, Deelen J, van der Most PJ, van der Laan SW, Arking DE, Morrison A, Dehghan A, Franco OH, Hofman A, Rivadeneira F, Sijbrands EJ, Uitterlinden AG, Mychaleckyj JC, Campbell A, Hocking LJ, Padmanabhan S, Brody JA, Rice KM, White CC, Harris T, Isaacs A, Campbell H, Lange LA, Rudan I, Kolcic I, Navarro P, Zemunik T, Salomaa V, LifeLines Cohort Study, Kooner AS, Kooner JS, Lehne B, Scott WR, Tan ST, de Geus EJ, Milaneschi Y, Penninx BW, Willemsen G, de Mutsert R, Ford I, Gansevoort RT, Segura-Lepe MP, Raitakari OT, Viikari JS, Nikus K, Forrester T, McKenzie CA, de Craen AJ, de Ruijter HM, Pasterkamp G, Snieder H, Oldehinkel AJ, Slagboom PE, Cooper RS, Kähönen M, Lehtimäki T, Elliott P, van der Harst P, Jukema JW, Mook-Kanamori DO, Boomsma DI, Chambers JC, Swertz M, Ripatti S, Willems van Dijk K, Vitart V, Polasek O, Hayward C, Wilson JG, Wilson JF, Gudnason V, Rich SS, Psaty BM, Borecki IB, Boerwinkle E, Rotter JI, Cupples LA, van Duijn CMet al., 2016, Meta-analysis of 49 549 individuals imputed with the 1000 Genomes Project reveals an exonic damaging variant in ANGPTL4 determining fasting TG levels, Journal of Medical Genetics, Vol: 53, Pages: 441-449, ISSN: 1468-6244

BACKGROUND: So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. METHODS: We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from ∼60 000 individuals in the discovery stage and ∼90 000 samples in the replication stage. RESULTS: Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. CONCLUSIONS: This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels.

Journal article

Zanoni P, Khetarpal SA, Larach DB, Hancock-Cerutti WF, Millar JS, Cuchel M, DerOhannessian S, Kontush A, Surendran P, Saleheen D, Trompet S, Jukema JW, De Craen A, Deloukas P, Sattar N, Ford I, Packard C, Majumder AAS, Alam DS, Di Angelantonio E, Abecasis G, Chowdhury R, Erdmann J, Nordestgaard BG, Nielsen SF, Tybjaerg-Hansen A, Schmidt RF, Kuulasmaa K, Liu DJ, Perola M, Blankenberg S, Salomaa V, Mannisto S, Amouyel P, Arveiler D, Ferrieres J, Muller-Nurasyid M, Ferrario M, Kee F, Willer CJ, Samani N, Schunkert H, Butterworth AS, Howson JMM, Peloso GM, Stitziel NO, Danesh J, Kathiresan S, Rader DJet al., 2016, Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease, SCIENCE, Vol: 351, Pages: 1166-1171, ISSN: 0036-8075

Journal article

Okuda N, Okayama A, Miura K, Yoshita K, Saito S, Nakagawa H, Sakata K, Miyagawa N, Chan Q, Elliott P, Ueshima H, Stamler Jet al., 2016, Food sources of dietary sodium in the Japanese adult population: the international study of macro-/micronutrients and blood pressure (INTERMAP), EUROPEAN JOURNAL OF NUTRITION, Vol: 56, Pages: 1269-1280, ISSN: 1436-6207

Journal article

Ghosh RE, Ashworth DC, Hansell AL, Garwood K, Elliott P, Toledano MBet al., 2016, Routinely collected English birth data sets: comparisons and recommendations for reproductive epidemiology., Archives of Disease in Childhood: Fetal and Neonatal edition, Vol: 101, Pages: F451-F457, ISSN: 1359-2998

BACKGROUND: In England there are four national routinely collected data sets on births: Office for National Statistics (ONS) births based on birth registrations; Hospital Episode Statistics (HES) deliveries (mothers' information); HES births (babies' information); and NHS Numbers for Babies (NN4B) based on ONS births plus gestational age and ethnicity information. This study describes and compares these data, with the aim of recommending the most appropriate data set(s) for use in epidemiological research and surveillance. METHODS: We assessed the completeness and quality of the data sets in relation to use in epidemiological research and surveillance and produced detailed descriptive statistics on common reproductive outcomes for each data set including temporal and spatial trends. RESULTS: ONS births is a high quality complete data set but lacks interpretive and clinical information. HES deliveries showed good agreement with ONS births but HES births showed larger amounts of missing or unavailable data. Both HES data sets had improved quality from 2003 onwards, but showed some local spatial variability. NN4B showed excellent agreement with ONS and HES deliveries for the years available (2006-2010). Annual number of births increased by 17.6% comparing 2002 with 2010 (ONS births). Approximately 6% of births were of low birth weight (2.6% term low birth weight) and 0.5% were stillbirths. CONCLUSIONS: Routinely collected data on births provide a valuable resource for researchers. ONS and NN4B offer the most complete and accurate record of births. Where more detailed clinical information is required, HES deliveries offers a high quality data set that captures the majority of English births.

Journal article

Gibson R, Eriksen R, Chan Q, Vergnaud AC, Singh D, Heard A, Spear J, Aresu M, McRobie D, Elliott P, Frost Get al., 2016, Sex differences in the relationship between work patterns and diet in British police force employees: a nested cross-sectional study, Proceedings of the Nutrition Society, Vol: 75, Pages: E20-E20, ISSN: 0029-6651

Journal article

Pattaro C, Teumer A, Gorski M, Chu AY, Li M, Mijatovic V, Garnaas M, Tin A, Sorice R, Li Y, Taliun D, Olden M, Foster M, Yang Q, Chen MH, Pers TH, Johnson AD, Ko YA, Fuchsberger C, Tayo B, Nalls M, Feitosa MF, Isaacs A, Dehghan A, d'Adamo P, Adeyemo A, Dieffenbach AK, Zonderman AB, Nolte IM, van der Most PJ, Wright AF, Shuldiner AR, Morrison AC, Hofman A, Smith AV, Dreisbach AW, Franke A, Uitterlinden AG, Metspalu A, Tonjes A, Lupo A, Robino A, Johansson Å, Demirkan A, Kollerits B, Freedman BI, Ponte B, Oostra BA, Paulweber B, Krämer BK, Mitchell BD, Buckley BM, Peralta CA, Hayward C, Helmer C, Rotimi CN, Shaffer CM, Müller C, Sala C, van Duijn CM, Saint-Pierre A, Ackermann D, Shriner D, Ruggiero D, Toniolo D, Lu Y, Cusi D, Czamara D, Ellinghaus D, Siscovick DS, Ruderfer D, Gieger C, Grallert H, Rochtchina E, Atkinson EJ, Holliday EG, Boerwinkle E, Salvi E, Bottinger EP, Murgia F, Rivadeneira F, Ernst F, Kronenberg F, Hu FB, Navis GJ, Curhan GC, Ehret GB, Homuth G, Coassin S, Thun GA, Pistis G, Gambaro G, Malerba G, Montgomery GW, Eiriksdottir G, Jacobs G, Li G, Wichmann HE, Campbell H, Schmidt H, Wallaschofski H, Völzke H, Brenner H, Kroemer HK, Kramer H, Lin H, Mateo Leach I, Ford I, Guessous I, Rudan I, Prokopenko I, Borecki I, Heid IM, Kolcic I, Persico I, Jukema JW, Wilson JF, Felix JF, Divers J, Lambert JC, Stafford JM, Gaspoz JM, Smith JA, Faul JD, Wang JJ, Ding J, Hirschhorn JN, Attia J, Whitfield JB, Chalmers J, Viikari J, Coresh J, Denny JC, Karjalainen J, Fernandes JK, Endlich K, Butterbach K, Keene KL, Lohman K, Portas L, Launer LJ, Lyytikäinen LP, Yengo L, Franke L, Ferrucci L, Rose LM, Kedenko L, Rao M, Struchalin M, Kleber ME, Cavalieri M, Haun M, Cornelis MC, Ciullo M, Pirastu M, de Andrade M, McEvoy MA, Woodward M, Adam M, Cocca M, Nauck M, Imboden M, Waldenberger M, Pruijm M, Metzger M, Stumvoll M, Evans MK, Sale MM, Kähönen M, Boban M, Bochud M, Rheinberger M, Verweij N, Bouatia-Naji N, Martin NG, Hastie N, Probst-Hensch N, Soranzo N, Devuyst O Ret al., 2016, Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function., Nat Commun, Vol: 7

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

Journal article

Chan Q, Stamler J, Griep LM, Daviglus ML, Horn LV, Elliott Pet al., 2015, An Update on Nutrients and Blood Pressure., Journal of Atherosclerosis and Thrombosis, Vol: 23, Pages: 276-289, ISSN: 1880-3873

Adverse blood pressure (BP) is a major independent risk factor for epidemic cardiovascular diseases affecting almost one-quarter of the adult population worldwide. Dietary intake is a major determinant in the development and progression of high BP. Lifestyle modifications, including recommended dietary guidelines, are advocated by the American Society of Hypertension, the International Society of Hypertension, the Japanese Society of Hypertension, and many other organisations for treating all hypertensive people, prior to initiating drug therapy and as an adjunct to medication in persons already on drug therapy. Lifestyle modification can also reduce high BP and prevent development of hypertension. This review synthesizes results from the International Study of Macro/Micronutrients and Blood Pressure (INTERMAP), a cross-sectional epidemiological study of 4,680 men and women aged 40-59 years from Japan, the People's Republic of China, the United Kingdom, and the United States, published over the past few years on cross cultural BP differences. INTERMAP has previously reported that intakes of vegetable protein, glutamic acid, total and insoluble fibre, total polyunsaturated fatty acid and linoleic acid, total n-3 fatty acid and linolenic acid, phosphorus, calcium, magnesium, and non-heme iron were inversely related to BP. Direct associations of sugars (fructose, glucose, and sucrose) and sugar-sweetened beverages (especially combined with high sodium intake), cholesterol, glycine, alanine, and oleic acid from animal sources with BP were also reported by the INTERMAP Study.

Journal article

Al Kuwari H, Al Thani A, Al Marri A, Al Kaabi A, Abderrahim H, Afifi N, Qafoud F, Chan Q, Tzoulaki I, Downey P, Ward H, Murphy N, Riboli E, Elliott Pet al., 2015, The Qatar Biobank: background and methods, BMC Public Health, Vol: 15, ISSN: 1471-2458

Background: The Qatar Biobank aims to collect extensive lifestyle, clinical, and biological information from up to60,000 men and women Qatari nationals and long-term residents (individuals living in the country for ≥15 years)aged ≥18 years (approximately one-fifth of all Qatari citizens), to follow up these same individuals over the longterm to record any subsequent disease, and hence to study the causes and progression of disease, and diseaseburden, in the Qatari population.Methods: Between the 11th-December-2012 and 20th-February-2014, 1209 participants were recruited into the pilotstudy of the Qatar Biobank. At recruitment, extensive phenotype information was collected from each participant,including information/measurements of socio-demographic factors, prevalent health conditions, diet, lifestyle,anthropometry, body composition, bone health, cognitive function, grip strength, retinal imaging, total body dualenergy X-ray absorptiometry, and measurements of cardiovascular and respiratory function. Blood, urine, and salivawere collected and stored for future research use. A panel of 66 clinical biomarkers was routinely measured onfresh blood samples in all participants. Rates of recruitment are to be progressively increased in the coming periodand the recruitment base widened to achieve a cohort of consented individuals broadly representative of theeligible Qatari population. In addition, it is planned to add additional measures in sub-samples of the cohort,including Magnetic Resonance Imaging (MRI) of the brain, heart and abdomen.Results: The mean time for collection of the extensive phenotypic information and biological samples from eachparticipant at the baseline recruitment visit was 179 min. The 1209 pilot study participants (506 men and 703women) were aged between 28–80 years (median 39 years); 899 (74.4 %) were Qatari nationals and 310 (25.6 %)were long-term residents. Approximately two-thirds of pilot participants were educated to graduate leve

Journal article

Vimaleswaran KS, Cavadino A, Verweij N, Nolte IM, Leach IM, Auvinen J, Veijola J, Elliott P, Penninx BW, Snieder H, Jarvelin M-R, van der Harst P, Cohen RD, Boucher BJ, Hyppoenen Eet al., 2015, Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study, European Journal of Endocrinology, Vol: 173, Pages: 863-872, ISSN: 1479-683X

Background and objective Given the role of uncoupling protein 2 (UCP2) in the accumulation of fat in the hepatocytes and in the enhancement of protective mechanisms in acute ethanol intake, we hypothesised that UCP2 polymorphisms are likely to cause liver disease through their interactions with obesity and alcohol intake. To test this hypothesis, we investigated the interaction between tagging polymorphisms in the UCP2 gene (rs2306819, rs599277 and rs659366), alcohol intake and obesity traits such as BMI and waist circumference (WC) on alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) in a large meta-analysis of data sets from three populations (n=20 242).Design and methods The study populations included the Northern Finland Birth Cohort 1966 (n=4996), Netherlands Study of Depression and Anxiety (n=1883) and LifeLines Cohort Study (n=13 363). Interactions between the polymorphisms and obesity and alcohol intake on dichotomised ALT and GGT levels were assessed using logistic regression and the likelihood ratio test.Results In the meta-analysis of the three cohorts, none of the three UCP2 polymorphisms were associated with GGT or ALT levels. There was no evidence for interaction between the polymorphisms and alcohol intake on GGT and ALT levels. In contrast, the association of WC and BMI with GGT levels varied by rs659366 genotype (Pinteraction=0.03 and 0.007, respectively; adjusted for age, gender, high alcohol intake, diabetes, hypertension and serum lipid concentrations).Conclusion In conclusion, our findings in 20 242 individuals suggest that UCP2 gene polymorphisms may cause liver dysfunction through the interaction with body fat rather than alcohol intake.

Journal article

Toledano MB, Smith RB, Chang I, Douglass M, Elliott Pet al., 2015, Cohort profile: UK COSMOS – a UK cohort for study of environment and health, International Journal of Epidemiology, Vol: 46, Pages: 775-787, ISSN: 1464-3685

Journal article

Aljuraiban GS, Griep LMO, Chan Q, Daviglus ML, Stamler J, Van Horn L, Elliott P, Frost GSet al., 2015, Total, insoluble and soluble dietary fibre intake in relation to blood pressure: the INTERMAP Study - CORRIGENDUM, British Journal of Nutrition, Vol: 114, Pages: 1534-1534, ISSN: 1475-2662

Journal article

Kato N, Loh M, Takeuchi F, Verweij N, Wang X, Zhang W, Kelly TN, Saleheen D, Lehne B, Leach IM, Drong AW, Abbott J, Wahl S, Tan S-T, Scott WR, Campanella G, Chadeau-Hyam M, Afzal U, Ahluwalia TS, Bonder MJ, Chen P, Dehghan A, Edwards TL, Esko T, Go MJ, Harris SE, Hartiala J, Kasela S, Kasturiratne A, Khor C-C, Kleber ME, Li H, Mok ZY, Nakatochi M, Sapari NS, Saxena R, Stewart AFR, Stolk L, Tabara Y, Teh AL, Wu Y, Wu J-Y, Zhang Y, Aits I, Alves ADSC, Das S, Dorajoo R, Hopewell JC, Kim YK, Koivula RW, Luan J, Lyytikainen L-P, Nguyen QN, Pereira MA, Postmus I, Raitakari OT, Bryan MS, Scott RA, Sorice R, Tragante V, Traglia M, White J, Yamamoto K, Zhang Y, Adair LS, Ahmed A, Akiyama K, Asif R, Aung T, Barroso I, Bjonnes A, Braun TR, Cai H, Chang L-C, Chen C-H, Cheng C-Y, Chong Y-S, Collins R, Courtney R, Davies G, Delgado G, Do LD, Doevendans PA, Gansevoort RT, Gao Y-T, Grammer TB, Grarup N, Grewal J, Gu D, Wander GS, Hartikainen A-L, Hazen SL, He J, Heng C-K, Hixson JE, Hofman A, Hsu C, Huang W, Husemoen LLN, Hwang J-Y, Ichihara S, Igase M, Isono M, Justesen JM, Katsuy T, Kibriya MG, Kim YJ, Kishimoto M, Koh W-P, Kohara K, Kumari M, Kwek K, Lee NR, Lee J, Liao J, Lieb W, Liewald DCM, Matsubara T, Matsushita Y, Meitinger T, Mihailov E, Milani L, Mills R, Mononen N, Mueller-Nurasyid M, Nabika T, Nakashima E, Ng HK, Nikus K, Nutile T, Ohkubo T, Ohnaka K, Parish S, Paternoster L, Peng H, Peters A, Pham ST, Pinidiyapathirage MJ, Rahman M, Rakugi H, Rolandsson O, Rozario MA, Ruggiero D, Sala CF, Sarju R, Shimokawa K, Snieder H, Sparso T, Spiering W, Starr JM, Stott DJ, Stram DO, Sugiyama T, Szymczak S, Tang WHW, Tong L, Trompet S, Turjanmaa V, Ueshima H, Uitterlinden AG, Umemura S, Vaarasmaki M, van Dam RM, van Gilst WH, van Veldhuisen DJ, Viikari JS, Waldenberger M, Wang Y, Wang A, Wilson R, Wong T-Y, Xiang Y-B, Yamaguchi S, Ye X, Young RD, Young TL, Yuan J-M, Zhou X, Asselbergs FW, Ciullo M, Clarke R, Deloukas P, Franke A, Franks PW, Franks S, Friedlander Y, Gross MD, Guoet al., 2015, Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation, Nature Genetics, Vol: 47, Pages: 1282-1293, ISSN: 1546-1718

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

Journal article

Newton JN, Briggs ADM, Murray CJL, Dicker D, Foreman KJ, Wang H, Naghavi M, Forouzanfar MH, Ohno SL, Barber RM, Vos T, Stanaway JRD, Schmidt JC, Hughes AJ, Fay DFJ, Ecob R, Gresser C, McKee M, Rutter H, Abubakar I, Ali R, Anderson HR, Banerjee A, Bennett DA, Bernabe E, Bhui KS, Biryukov SM, Bourne RR, Brayne CEG, Bruce NG, Brugha TS, Burch M, Capewell S, Casey D, Chowdhury R, Coates MM, Cooper C, Critchley JA, Dargan PI, Dherani MK, Elliott P, Ezzati M, Fenton KA, Fraser MS, Fuerst T, Greaves F, Green MA, Gunnell DJ, Hannigan BM, Hay RJ, Hay SI, Hemingway H, Larson HJ, Looker KJ, Lunevicius R, Lyons RA, Marcenes W, Mason-Jones AJ, Matthews FE, Moller H, Murdoch ME, Newton CR, Pearce N, Piel FB, Pope D, Rahimi K, Rodriguez A, Scarborough P, Schumacher AE, Shiue I, Smeeth L, Tedstone A, Valabhji J, Williams HC, Wolfe CDA, Woolf AD, Davis ACJet al., 2015, Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013, Lancet, Vol: 386, Pages: 2257-2274, ISSN: 1474-547X

Journal article

Aljuraiban GS, Oude Griep LM, Chan Q, Daviglus ML, Stamler J, Van Horn L, Elliott P, Frost GSet al., 2015, Total, insoluble and soluble dietary fibre intake in relation to blood pressure: the INTERMAP Study., British Journal of Nutrition, Vol: 114, Pages: 1480-1486, ISSN: 1475-2662

Prospective cohort studies have shown inverse associations between fibre intake and CVD, possibly mediated by blood pressure (BP). However, little is known about the impact of types of fibre on BP. We examined cross-sectional associations with BP of total, insoluble and soluble fibre intakes. Data were used from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP) study, including 2195 men and women aged between 40 and 59 years from the USA. During four visits, eight BP, four 24 h dietary recalls and two 24 h urine samples were collected. Linear regression models adjusted for lifestyle and dietary confounders to estimate BP differences per 2 sd higher intakes of total and individual types of fibre were calculated. After multivariable adjustment, total fibre intake higher by 6·8 g/4184 kJ (6·8 g/1000 kcal) was associated with a 1·69 mmHg lower systolic blood pressure (SBP; 95 % CI -2·97, -0·41) and attenuated to -1·01 mmHg (95 % CI -2·35, 0·34) after adjustment for urinary K. Insoluble fibre intake higher by 4·6 g/4184 kJ (4·6 g/1000 kcal) was associated with a 1·81 mmHg lower SBP (95 % CI -3·65, 0·04), additionally adjusted for soluble fibre and urinary K excretion, whereas soluble fibre was not associated with BP. Raw fruit was the main source of total and insoluble fibre, followed by whole grains and vegetables. In conclusion, higher intakes of fibre, especially insoluble, may contribute to lower BP, independent of nutrients associated with higher intakes of fibre-rich foods.

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