Paul Elliott

Imperial College London, Londinium, England, United Kingdom

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Publications (295)3256.04 Total impact

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    ABSTRACT: DNA methylation plays a fundamental role in the regulation of the genome, but the optimal strategy for analysis of genome-wide DNA methylation data remains to be determined. We developed a comprehensive analysis pipeline for epigenome-wide association studies (EWAS) using the Illumina Infinium HumanMethylation450 BeadChip, based on 2,687 individuals, with 36 samples measured in duplicate. We propose new approaches to quality control, data normalisation and batch correction through control-probe adjustment and establish a null hypothesis for EWAS using permutation testing. Our analysis pipeline outperforms existing approaches, enabling accurate identification of methylation quantitative trait loci for hypothesis driven follow-up experiments. Electronic supplementary material The online version of this article (doi:10.1186/s13059-015-0600-x) contains supplementary material, which is available to authorized users.
    Genome Biology 12/2015; 16(1). DOI:10.1186/s13059-015-0600-x · 10.81 Impact Factor

  • European Journal of Endocrinology 12/2015; 173(6):863-872. DOI:10.1530/EJE-15-0839 · 4.07 Impact Factor

  • International Journal of Epidemiology 11/2015; DOI:10.1093/ije/dyv203 · 9.18 Impact Factor
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    ABSTRACT: High blood pressure, which affects more than 1 billion people worldwide , is a major risk factor for myocardial infarction, stroke and chronic kidney disease. Approximately 9 million deaths each year are attributable to high blood pressure, including >50% of deaths from coronary heart disease and stroke 1,2. High blood pressure is more prevalent in people of East Asian and South Asian ancestry and is a major contributor to their increased risk of stroke and coronary heart disease 3,4. Genome-wide association studies (GWAS) have identified over 50 genetic loci influencing blood pressure in predominantly European populations 5–16. A role for epigenetic mechanisms in blood pressure regulation has also been suggested 17–20. We carried out a GWAS in East Asians and South Asians, as well as Europeans, to seek both cosmopolitan and population-specific genetic effects for five blood pressure phenotypes: systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, mean arterial pressure (MAP) and hypertension (Supplementary Fig. 1) (ref. 5). We then sought DNA coding and gene regulatory mechanisms, including DNA methylation and gene transcription, to help explain the relationships we observed between sequence variation and blood pressure. RESULTS Genome-wide association and replication testing We used genome-wide association data from 99,994 individuals of East Asian (n = 31,516), European (n = 35,352) and South Asian (n = 33,126) ancestry. Characteristics of the participants and information on the genotyping arrays and imputation are summarized in Supplementary Tables 1–3. Phenotype-specific meta-analysis was carried out separately for East Asian, European and South Asian samples, followed by a meta-analysis across the three ancestral population groups. The trans-ancestry genome-wide association results identified 4,077 variants with P < 1 × 10 −4 against any blood pressure phenotype, distributed among 630 genetic loci. At each locus, we identified the sentinel SNP (the SNP with the lowest P value against any phenotype) and carried out combined analysis with phenotype-specific results from the International Consortium on Blood Pressure (ICBP) GWAS (maximum n = 87,205) (refs. 8,9). This analysis identified 19 previously unreported loci where the sentinel SNP had suggestive evidence for association with blood pressure (P < 1 × 10 −7
    Nature Genetics 09/2015; DOI:10.1038/ng.3405 · 29.35 Impact Factor
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    ABSTRACT: 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.
    The British journal of nutrition 09/2015; 114(9). DOI:10.1017/S0007114515003098 · 3.45 Impact Factor
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    ABSTRACT: This study examined the impact of overweight/obesity on sodium, potassium, and blood pressure associations using the Shandong-Ministry of Health Action on Salt Reduction and Hypertension (SMASH) project baseline survey data. Twenty-four-hour urine samples were collected in 1948 Chinese adults aged 18 to 69 years. The observed associations of sodium, potassium, sodium-potassium ratio, and systolic blood pressure (SBP) were stronger in the overweight/obese population than among those of normal weight. Among overweight/obese respondents, each additional standard deviation (SD) higher of urinary sodium excretion (SD=85 mmol) and potassium excretion (SD=19 mmol) was associated with a 1.31 mm Hg (95% confidence interval, 0.37-2.26) and -1.43 mm Hg (95% confidence interval, -2.23 to -0.63) difference in SBP, and each higher unit in sodium-potassium ratio was associated with a 0.54 mm Hg (95% confidence interval, 0.34-0.75) increase in SBP. The association between sodium, potassium, sodium-potassium ratio, and prevalence of hypertension among overweight/obese patients was similar to that of SBP. Our study indicated that the relationships between BP and both urinary sodium and potassium might be modified by BMI status in Chinese adults. © 2015 Wiley Periodicals, Inc.
    Journal of Clinical Hypertension 08/2015; DOI:10.1111/jch.12658 · 2.85 Impact Factor
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    ABSTRACT: The EU-FP7-funded BioSHaRE project is using individual-level data pooled from several national cohort studies in Europe to investigate the relationship of road traffic noise and health. The detailed input data (land cover and traffic characteristics) required for noise exposure modelling are not always available over whole countries while data that are comparable in spatial resolution between different countries is needed for harmonised exposure assessment. Here, we assess the feasibility using the CNOSSOS-EU road traffic noise prediction model with coarser input data in terms of model performance. Starting with a model using the highest resolution datasets, we progressively introduced lower resolution data over five further model runs and compared noise level estimates to measurements. We conclude that a low resolution noise model should provide adequate performance for exposure ranking (Spearman's rank = 0.75; p < 0.001), but with relatively large errors in predicted noise levels (RMSE = 4.46 dB(A)). Copyright © 2015 Elsevier Ltd. All rights reserved.
    Environmental Pollution 07/2015; 206:332-341. DOI:10.1016/j.envpol.2015.07.031 · 4.14 Impact Factor
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    Alasdair Philips · Paul Elliott · Mireille B. Toledano ·

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    ABSTRACT: Large-scale prospective cohort studies are invaluable in epidemiology, but they are increasingly difficult and costly to establish and follow-up. More efficient methods for recruitment, data collection and follow-up are essential if such studies are to remain feasible with limited public and research funds. Here, we discuss how these challenges were addressed in the UK COSMOS cohort study where fixed budget and limited time frame necessitated new approaches to consent and recruitment between 2009-2012. Web-based e-consent and data collection should be considered in large scale observational studies, as they offer a streamlined experience which benefits both participants and researchers and save costs. Commercial providers of register and marketing data, smartphones, apps, email, social media, and the internet offer innovative possibilities for identifying, recruiting and following up cohorts. Using examples from UK COSMOS, this article sets out the dos and don’ts for today's cohort studies and provides a guide on how best to take advantage of new technologies and innovative methods to simplify logistics and minimise costs. Thus a more streamlined experience to the benefit of both research participants and researchers becomes achievable.
    PLoS ONE 07/2015; 10(7). DOI:10.1371/journal.pone.0131521 · 3.23 Impact Factor
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    ABSTRACT: Low-carbohydrate diets (LCD) are a popular dietary strategy for weight reduction. The effects of LCD on long-term outcome vary depending on type of LCD, possibly due to the fact that effects on cardiometabolic risk factors may vary with different types of LCD. Accordingly, we studied these relations. We assessed serum concentrations of high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), high-sensitivity C-reactive protein (CRP), total cholesterol, glycated hemoglobin, and uric acid, and nutrient intakes by standardized methods in men and women ages 40-59 years from four population samples of Japanese in Japan (553 men and 544 women, combined). For people consuming usual, animal-based, and plant-based LCDs, we calculated LCD scores, based on relative level of fat, protein, and carbohydrate, by modifying the methods of Halton et al. Instead of calculating scores based on animal or vegetable fat, we used saturated fatty acids (SFA) or monounsaturated fatty acids (MUFA) + polyunsaturated fatty acids (PUFA). In multivariate regression analyses with adjustment for site, age, sex, BMI, smoking, alcohol intake, physical activity, and years of education, all three LCD scores were significantly positively related to HDLc (all P < 0.001), but not to LDLc. The plant-based LCD score was significantly inversely related to log CRP (coefficient = -0.010, P = 0.018). All three LCD scores were significantly positively related to HDLc. The plant-based LCD score was significantly inversely related to CRP. Carbohydrate intake below 50 % of total energy with higher intakes of vegetable protein and MUFA + PUFA, and lower intakes of SFA may be favorable for reducing cardiometabolic risk factors.
    European Journal of Nutrition 06/2015; DOI:10.1007/s00394-015-0969-z · 3.47 Impact Factor
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    ABSTRACT: Indian Asians, who make up a quarter of the world's population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes. We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p<1 × 10(-7). We compared methylation levels between Indian Asian and European controls without type 2 diabetes at baseline to estimate the potential contribution of DNA methylation to increased risk of future type 2 diabetes incidence among Indian Asians. 1608 (11·9%) of 13 535 Indian Asians and 306 (4·3%) of 7066 Europeans developed type 2 diabetes over a mean of 8·5 years (SD 1·8) of follow-up. The age-adjusted and sex-adjusted incidence of type 2 diabetes was 3·1 times (95% CI 2·8-3·6; p<0·0001) higher among Indian Asians than among Europeans, and remained 2·5 times (2·1-2·9; p<0·0001) higher after adjustment for adiposity, physical activity, family history of type 2 diabetes, and baseline glycaemic measures. The mean absolute difference in methylation level between type 2 diabetes cases and controls ranged from 0·5% (SD 0·1) to 1·1% (0·2). Methylation markers at five loci were associated with future type 2 diabetes incidence; the relative risk per 1% increase in methylation was 1·09 (95% CI 1·07-1·11; p=1·3 × 10(-17)) for ABCG1, 0·94 (0·92-0·95; p=4·2 × 10(-11)) for PHOSPHO1, 0·94 (0·92-0·96; p=1·4 × 10(-9)) for SOCS3, 1·07 (1·04-1·09; p=2·1 × 10(-10)) for SREBF1, and 0·92 (0·90-0·94; p=1·2 × 10(-17)) for TXNIP. A methylation score combining results for the five loci was associated with future type 2 diabetes incidence (relative risk quartile 4 vs quartile 1 3·51, 95% CI 2·79-4·42; p=1·3 × 10(-26)), and was independent of established risk factors. Methylation score was higher among Indian Asians than Europeans (p=1 × 10(-34)). DNA methylation might provide new insights into the pathways underlying type 2 diabetes and offer new opportunities for risk stratification and prevention of type 2 diabetes among Indian Asians. The European Union, the UK National Institute for Health Research, the Wellcome Trust, the UK Medical Research Council, Action on Hearing Loss, the UK Biotechnology and Biological Sciences Research Council, the Oak Foundation, the Economic and Social Research Council, Helmholtz Zentrum Munchen, the German Research Center for Environmental Health, the German Federal Ministry of Education and Research, the German Center for Diabetes Research, the Munich Center for Health Sciences, the Ministry of Science and Research of the State of North Rhine-Westphalia, and the German Federal Ministry of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.
    06/2015; 3(7). DOI:10.1016/S2213-8587(15)00127-8
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    ABSTRACT: Ischaemic heart disease, stroke, and other cardiovascular diseases (CVDs) lead to 17.5 million deaths worldwide per year. Taking into account population ageing, CVD death rates are decreasing steadily both in regions with reliable trend data and globally. The declines in high-income countries and some Latin American countries have been ongoing for decades without slowing. These positive trends have broadly coincided with, and benefited from, declines in smoking and physiological risk factors, such as blood pressure and serum cholesterol levels. These declines have also coincided with, and benefited from, improvements in medical care, including primary prevention, diagnosis, and treatment of acute CVDs, as well as post-hospital care, especially in the past 40 years. These variables, however, explain neither why the decline began when it did, nor the similarities and differences in the start time and rate of the decline between countries and sexes. In Russia and some other former Soviet countries, changes in volume and patterns of alcohol consumption have caused sharp rises in CVD mortality since the early 1990s. An important challenge in reaching firm conclusions about the drivers of these remarkable international trends is the paucity of time-trend data on CVD incidence, risk factors throughout the life-course, and clinical care.
    Nature Reviews Cardiology 06/2015; 12(9). DOI:10.1038/nrcardio.2015.82 · 9.18 Impact Factor
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    ABSTRACT: This article summarizes current data and approaches to assess sodium intake in individuals and populations. A review of the literature on sodium excretion and intake estimation supports the continued use of 24-h urine collections for assessing population and individual sodium intake. Since 2000, 29 studies used urine biomarkers to estimate population sodium intake, primarily among adults. More than half used 24-h urine; the rest used a spot/casual, overnight, or 12-h specimen. Associations between individual sodium intake and health outcomes were investigated in 13 prospective cohort studies published since 2000. Only three included an indicator of long-term individual sodium intake, i.e., multiple 24-h urine specimens collected several days apart. Although not insurmountable, logistic challenges of 24-h urine collection remain a barrier for research on the relationship of sodium intake and chronic disease. Newer approaches, including modeling based on shorter collections, offer promise for estimating population sodium intake in some groups. Expected final online publication date for the Annual Review of Nutrition Volume 35 is July 17, 2015. Please see for revised estimates.
    Annual Review of Nutrition 05/2015; 35(1). DOI:10.1146/annurev-nutr-071714-034322 · 8.36 Impact Factor
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    ABSTRACT: Obesity is a major public health problem worldwide. We used 24-hour urinary metabolic profiling by proton (1H) nuclear magnetic resonance (NMR) spectroscopy and ion exchange chromatography to characterize the metabolic signatures of adiposity in the U.S. (n = 1880) and UK (n = 444) cohorts of the INTERMAP (International Study of Macro- and Micronutrients and Blood Pressure) epidemiologic study. Metabolic profiling of urine samples collected over two 24-hour time periods 3 weeks apart showed reproducible patterns of metabolite excretion associated with adiposity. Exploratory analysis of the urinary metabolome using 1H NMR spectroscopy of the U.S. samples identified 29 molecular species, clustered in interconnecting metabolic pathways, that were significantly associated (P = 1.5 × 10-5 to 2.0 × 10-36) with body mass index (BMI); 25 of these species were also found in the UK validation cohort. We found multiple associations between urinary metabolites and BMI including urinary glycoproteins and N-acetyl neuraminate (related to renal function), trimethylamine, dimethylamine, 4-cresyl sulfate, phenylacetylglutamine and 2-hydroxyisobutyrate (gut microbial co-metabolites), succinate and citrate (tricarboxylic acid cycle intermediates), ketoleucine and the ketoleucine/leucine ratio (linked to skeletal muscle mitochondria and branched-chain amino acid metabolism), ethanolamine (skeletal muscle turnover), and 3-methylhistidine (skeletal muscle turnover and meat intake). We mapped the multiple BMI-metabolite relationships as part of an integrated systems network that describes the connectivities between the complex pathway and compartmental signatures of human adiposity. Copyright
    Science translational medicine 04/2015; 7(285):285ra62-285ra62. DOI:10.1126/scitranslmed.aaa5680 · 15.84 Impact Factor
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    ABSTRACT: Cathie Sudlow and colleagues describe the UK Biobank, a large population-based prospective study, established to allow investigation of the genetic and non-genetic determinants of the diseases of middle and old age.
    PLoS Medicine 03/2015; 12(3):e1001779. DOI:10.1371/journal.pmed.1001779 · 14.43 Impact Factor
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    Queenie Chan · Jeremiah Stamler · Paul Elliott ·
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    ABSTRACT: Adverse blood pressure (BP) is a major independent risk factor for epidemic cardiovascular diseases affecting almost one third of the US adult population. This review synthesizes results from studies published over the past few years on BP differences and prevalent hypertension between US blacks and whites and their different intakes of foods (e.g., fruits, vegetables, and dairy products) and micronutrients (e.g., vitamin D, calcium, potassium, and phosphorus). Studies have consistently reported higher prevalence of adverse BP levels and hypertension and less favorable dietary intakes in blacks than in whites, but the influence of specific dietary factors on high BP risk for blacks remains unclear.
    Current Hypertension Reports 02/2015; 17(2):517. DOI:10.1007/s11906-014-0517-x · 3.44 Impact Factor
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    ABSTRACT: Background—Epidemiologic evidence is sparse on the effect of dietary behaviors and diet quality on body mass index (BMI) that may be important drivers of the obesity epidemic. Objective—This study investigated the relationships of frequency of eating and time of intake to energy density, nutrient quality and BMI using data from the INTERnational study on MAcro/ micronutrients and blood Pressure (INTERMAP) including 2,696 men and women aged 40-59 from the United States and the United Kingdom. Design—INTERMAP is a cross-sectional investigation with four 24-hour dietary recalls and BMI measurements conducted between 1996 and 1999. Consumption of solid foods was aggregated into eating occasion. Nutrient density is expressed using the Nutrient Rich Food (NRF 9.3) index. The ratio of evening/morning energy intake was calculated; mean values of four visits were used. Statistical analyses performed—Characteristics across eating occasion categories are presented as adjusted mean with corresponding 95% confidence interval. Multiple linear regression models were used to examine associations of eating occasions, ratio of evening/ morning energy intake, dietary energy density, and NRF 9.3 index with BMI. Results—Compared to participants with < 4 eating occasions/24-hours, those with ≥ 6 eating occasions/24-hours had lower mean: BMI: 27.3 vs. 29.0 kg/m2; total energy intake: 2,129 vs. 2,472 kcal/24-hours; dietary energy density: 1.5 vs. 2.1 kcal/g; and higher NRF 9.3 index: 34.3 vs. 28.1. In multiple regression analyses, higher evening intake relative to morning intake was directly associated with BMI; however this did not influence the relationship between eating frequency and BMI. Conclusions—Our results suggest that a larger number of small meals may be associated with improved diet quality and lower BMI. This may have implications for behavioral approaches to controlling the obesity epidemic.
    Journal of the American Academy of Nutrition and Dietetics 01/2015; 115(4). DOI:10.1016/j.jand.2014.11.017 · 3.47 Impact Factor
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    ABSTRACT: Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24±4 kg/m2). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%-183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87%±3%; R2 = 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160%±2%; R2 = 0.92). Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.
    PLoS Medicine 12/2014; 11(12):e1001765. DOI:10.1371/journal.pmed.1001765 · 14.43 Impact Factor

Publication Stats

22k Citations
3,256.04 Total Impact Points


  • 1998-2015
    • Imperial College London
      • • Department of Epidemiology and Biostatistics
      • • School of Public Health
      • • Faculty of Medicine
      Londinium, England, United Kingdom
  • 2010-2013
    • University of Oulu
      • Institute of Health Sciences
      Uleoborg, Northern Ostrobothnia, Finland
    • University of Lausanne
      • Department of Medical Genetics
      Lausanne, VD, Switzerland
  • 2012
    • University of Gothenburg
      • Department of Molecular and Clinical Medicine
      Göteborg, Vaestra Goetaland, Sweden
    • Wake Forest School of Medicine
      Winston-Salem, North Carolina, United States
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
  • 2010-2011
    • Imperial Valley College
      Imperial, California, United States
  • 1998-2006
    • Imperial College Healthcare NHS Trust
      Londinium, England, United Kingdom
  • 2005
    • King's College London
      • Department of Nutrition and Dietetics
      London, ENG, United Kingdom
  • 1995-2005
    • Northwestern University
      • • Division of Gastroenterology and Hepatology
      • • Department of Preventive Medicine
      Evanston, Illinois, United States
  • 2001
    • The University of Edinburgh
      • School of Clinical Sciences and Community Health
      Edinburgh, Scotland, United Kingdom
  • 1995-1996
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom