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

Takashima N, Ohkubo T, Miura K, Okayama A, Nagako O, Nakagawa H, Saito S, Sakata K, Choudhury SR, Miyagawa N, Chan Q, Zhao L, Elliott P, Ueshima H, Stamler Jet al., 2018, Factors associated with intra-individual visit-to-vist variability in blood pressure in four countries: The INTERMAP Study, Journal of Human Hypertension, Vol: 33, Pages: 229-236, ISSN: 0950-9240

Several studies demonstrated that visit-to-visit variability of blood pressure (BP) predicted future events of total death, stroke and cardiovascular disease. Little is known about factors associated with visit-to-visit BP variability in different countries. We recruited participants aged 40–59 years from four countries (Japan, the People’s Republic of China [PRC], the United Kingdom [UK] and the United States [US]). At each study visit, BP was measured twice by trained observers using random zero sphygmomanometers after five minutes resting. We defined visit-to-visit BP variability as variation independent of mean (VIM) by using average systolic BP of 1st and 2nd measurement across four study visits. Data on 4680 men and women were analyzed. Mean ± standard deviation of VIM values among participants in Japan, the PRC, the UK and the US were 5.44 ± 2.88, 6.85 ± 3.49, 5.65 ± 2.81 and 5.84 ± 3.01, respectively; VIM value in the PRC participants was significantly higher. Sensitivity analyses among participants without antihypertensive treatment or past history of cardiovascular disease yielded similar results. Higher VIM value was associated with older age, female gender, lower pulse rate and urinary sodium excretion and use of antihypertensive agents such as angiotensin converting enzyme inhibitors, beta blockers and calcium channel blockers. The difference of visit-to-visit BP variability between PRC and other countries remained significant after adjustment for possible confounding factors. In this large international study across four countries, visit-to-visit BP variability in the PRC was higher than in the other three countries. Reproducibility and mechanisms of these findings remain to be elucidated.

Journal article

Gill D, Georgakis MK, Koskeridis F, Jiang L, Feng Q, Wei W-Q, Theodoratou E, Elliott P, Denny JC, Malik R, Evangelou E, Dehghan A, Dichgans M, Tzoulaki Iet al., 2018, Genetic variants related to antihypertensive targets inform drug efficacy and side effects, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Drug effects can be investigated through natural variation in the genes for their protein targets. We aimed to use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs, which are amongst the most commonly used medications worldwide.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We identified genetic instruments for antihypertensive drug classes as variants in the gene for the corresponding target that associated with systolic blood pressure at genome-wide significance. To validate the instruments, we compared Mendelian randomisation (MR) estimates for drug effects on coronary heart disease (CHD) and stroke risk to randomised controlled trial (RCT) results. Phenome-wide association study (PheWAS) in the UK Biobank was performed to identify potential side effects and repurposing opportunities, with findings investigated in the Vanderbilt University Biobank (BioVU) and in observational analysis of the UK Biobank.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>We identified suitable genetic instruments for beta-blockers (BBs) and calcium channel blockers (CCBs). MR estimates for their effect on CHD and stroke risk respectively were comparable to results from RCTs against placebo. PheWAS in the UK Biobank identified an association of the CCB genetic risk score (scaled to drug effect) with increased risk of diverticulosis (odds ratio [OR] 1.23, 95%CI 1.10-1.38), with a consistent estimate found in BioVU (OR 1.16, 95%CI 0.94-1.44). Association with diverticulosis was further supported in observational analysis of CCB use in the UK Biobank (OR 1.08, 95%CI 1.02-1.15).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>We identifi

Working paper

Vergnaud A-C, Aresu M, Kongsgård HW, McRobie D, Singh D, Spear J, Heard A, Gao H, Carpenter JR, Elliott Pet al., 2018, Estimation of TETRA radio use in the Airwave Health Monitoring Study of the British police forces, Environmental Research, Vol: 167, Pages: 169-174, ISSN: 0013-9351

BACKGROUND: The Airwave Health Monitoring Study aims to investigate the possible long-term health effects of Terrestrial Trunked Radio (TETRA) use among the police forces in Great Britain. Here, we investigate whether objective data from the network operator could be used to correct for misreporting in self-reported data and expand the radio usage availability in our cohort. METHODS: We estimated average monthly usage of personal radio in the 12 months prior to enrolment from a missing value imputation model and evaluated its performance against objective and self-reported data. Factors associated with TETRA radio usage variables were investigated using Chi-square tests and analysis of variance. RESULTS: The imputed data were better correlated with objective than self-reported usage (Spearman correlation coefficient = 0.72 vs. 0. 52 and kappa 0.56 [95% confidence interval 0.55, 0.56] vs. 0.46 [0.45, 0.47]), although the imputation model tended to under-estimate use for higher users. Participants with higher personal radio usage were more likely to be younger, men vs. women and officer vs. staff. The median average monthly usage level for the entire cohort was estimated to be 29.3 min (95% CI: [7.2, 66.6]). CONCLUSION: The availability of objective personal radio records for a large proportion of users allowed us to develop a robust imputation model and hence obtain personal radio usage estimates for ~50,000 participants. This substantially reduced exposure misclassification compared to using self-reported data and will allow us to carry out analyses of TETRA usage for the entire cohort in future work.

Journal article

Evangelou E, Gao H, Chu C, Ntritsos G, Blakeley P, Butts A, Pazoki R, Suzuki H, Koskeridis F, Yiorkas A, Karaman I, Elliott J, Aeschbacher S, Bartz T, Baumeister S, Braund P, Brown M, Brody J, Clarke T-K, Dimou N, Faul J, Homuth G, Jackson A, Kentistou K, Joshi P, Lemaitre R, Lind P, Lyytikäinen L-P, Mangino M, Milaneschi Y, Nelson C, Nolte I, Perälä M-M, Polasek O, Porteous D, Ratliff S, Smith J, Stančáková A, Teumer A, Tuominen S, Thériault S, Vangipurapu J, Whitfield J, Wood A, Yao J, Yu B, Zhao W, Arking D, Auvinen J, Liu C, Männikkö M, Risch L, Rotter J, Snieder H, Veijola J, Blakemore A, Boehnke M, Campbell H, Conen D, Eriksson J, Grabe H, Guo X, Harst PVD, Hartman C, Hayward C, Heath A, Jarvelin M-R, Kähönen M, Kardia SLR, Kühne M, Kuusisto J, Laakso M, Lahti J, Lehtimäki T, McIntosh A, Mohlke K, Morrison A, Martin N, Oldehinkel A, Penninx BWJH, Psaty B, Raitakari O, Rudan I, Samani N, Scott L, Spector T, Verweij N, Weir D, Wilson J, Levy D, Tzoulaki I, Bell J, Matthews P, Rothenfluh A, Desrivières S, Schumann G, Elliott Pet al., 2018, Genome-wide association and functional studies identify 46 novel loci for alcohol consumption and suggest common genetic mechanisms with neuropsychiatric disorders, bioRxiv The preprint server for biology

Abstract Excessive alcohol consumption is one of the main causes of death and disability worldwide. Alcohol consumption is a heritable complex trait. We conducted a genome-wide association study (GWAS) of alcohol use in ~480,000 people of European descent to decipher the genetic architecture of alcohol intake. We identified 46 novel, common loci, and investigated their potential functional significance using magnetic resonance imaging data, gene expression and behavioral studies in Drosophila . Our results identify new genetic pathways associated with alcohol consumption and suggest common genetic mechanisms with several neuropsychiatric disorders including schizophrenia.

Journal article

Chekmeneva E, Dos Santos Correia G, Gomez Romero M, Stamler J, Chan Q, Elliott P, Nicholson J, Holmes Eet al., 2018, Ultra performance liquid chromatography-high resolution mass spectrometry and direct infusion-high resolution mass spectrometry for combined exploratory and targeted metabolic profiling of human urine, Journal of Proteome Research, Vol: 17, Pages: 3492-3502, ISSN: 1535-3893

The application of metabolic phenotyping to epidemiological studies involving thousands of biofluid samples presents a challenge for the selection of analytical platforms that meet the requirements of high-throughput precision analysis and cost-effectiveness. Here, direct infusion nanoelectrospray (DI-nESI)- was compared to an ultra-performance (UPLC)-high resolution mass spectrometry (HRMS) method for metabolic profiling of an exemplary set of 132 human urine samples from a large epidemiological cohort. Both methods were developed and optimised to allow simultaneous collection of high resolution urinary metabolic profiles and quantitative data for a selected panel of 35 metabolites. The total run time for measuring the sample set in both polarities by UPLC-HRMS was of 5 days compared to 9 hours by DI-nESI-HRMS. To compare the classification ability of the two MS methods we performed exploratory analysis of the full-scan HRMS profiles to detect sex-related differences in biochemical composition. Although metabolite identification is less specific in DI-nESI-HRMS, the significant features responsible for discrimination between sexes were mostly the same in both MS-based platforms. Using the quantitative data we showed that 10 metabolites have strong correlation (Pearson’s r > 0.9 and Passing-Bablok regression slope 0.8-1.3) and good agreement assessed by Bland-Altman plots between UPLC-HRMS and DI-nESI-HRMS and thus, can be measured using a cheaper and less sample- and time-consuming method. Only five metabolites showed weak correlation (Pearson’s r< 0.4) and poor agreement due to the overestimation of the results by DI-nESI-HRMS, and the rest of metabolites showed acceptable correlation between the two methods.

Journal article

Huang L, Tian M, Li N, Elliot P, Yan L, Labarthe D, Yin X, Wu Y, Hao Z, Liu Y, Shi J, Feng X, Zhang J, Zhang Y, Zhang R, Neal Bet al., 2018, A13076 Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS), 27th Scientific Meeting of the International-Society-of-Hypertension, Publisher: Lippincott, Williams & Wilkins, Pages: E279-E279, ISSN: 0263-6352

Conference paper

De Silva M, Sebert S, Alves AC, Sovio U, Das S, Taal RH, Warrington N, Lewin AM, Kaakinen M, Cousminer D, Thiering E, Timpson N, Karhunen V, Bond T, Estivill X, Lindi V, Bradfield JP, Geller F, Coin LJM, Loh M, Barton SJ, Beilin LJ, Bisgaard H, Bonnelykke K, Alili R, Ahluwalia T, Marinelli M, Millwood IY, Palmer LJ, Pennell CE, Perry JR, Ring SM, Savolainen M, Stefansson K, Rivadeneira F, Standl M, Sunyer J, Tiesler CMT, Uitterlinden AG, Prokopenko I, Herzig K, Smith GD, Buxton JL, Blakemore AF, Ong K, Grant SFA, Jaddoe VWV, O'Reilly P, McCarthy MI, Jarvelin Met al., 2018, Genetic architecture of early growth phenotypes gives insights into their link with later obesity, Publisher: NATURE PUBLISHING GROUP

Working paper

Aljuraiban GS, Stamler J, Chan Q, Van Horn L, Daviglus ML, Elliott P, Oude Griep LM, INTERMAP Research Groupet al., 2018, Relations between dairy product intake and blood pressure: the INTERnational study on MAcro/micronutrients and blood Pressure, Journal of Hypertension, Vol: 36, Pages: 2049-2058, ISSN: 0263-6352

BACKGROUND: Epidemiologic evidence suggests that low-fat dairy consumption may lower risk of hypertension. Dairy products may be distinctly linked to health, because of differences in nutritional composition, but little is known about specific nutrients that contribute to the dairy-blood pressure (BP) association, nor to underlying kidney function. METHODS: We examined cross-sectional associations to BP of dairy product intakes, total and by type, from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP) including 2694 participants aged 40-59 years from the UK and the USA. Eight BP, four 24-h dietary recalls and two 24-h urine samples were collected during four visits. Linear regression models adjusted for lifestyle/dietary factors to estimate BP differences per 2SD higher intakes of total-and-individual-types of dairy were calculated. RESULTS: Multivariable linear regression coefficients were estimated and pooled. In contrast to total and whole-fat dairy, each 195 g/1000 kcal (2SD) greater low-fat dairy intake was associated with a lower SBP -2.31 mmHg and DBP -2.27 mmHg. Significant associations attenuated with adjustment for dietary phosphorus, calcium, and lactose, but strengthened with urinary calcium adjustment. Stratification by median albumin-creatinine ratio (ACR; high ACR indicates impaired kidney function) showed strong associations between low-fat dairy and BP in participants with low ACR (SBP: -3.66; DBP: -2.15 mmHg), with no association in participants with high ACR. CONCLUSION: Low-fat dairy consumption was associated with lower BP, especially among participants with low ACR. Dairy-rich nutrients including phosphorus and calcium may have contributed to the beneficial associations with BP.

Journal article

Zaid M, Miura K, Okayama A, Nakagawa H, Sakata K, Saitoh S, Okuda N, Yoshita K, Choudhury SR, Rodriguez B, Masaki K, Willcox B, Miyagawa N, Okamura T, Chan Q, Elliott P, Stamler J, Ueshima Het al., 2018, Associations of High-Density Lipoprotein Particle and High-Density Lipoprotein Cholesterol With Alcohol Intake, Smoking, and Body Mass Index - The INTERLIPID Study -, CIRCULATION JOURNAL, Vol: 82, Pages: 2557-+, ISSN: 1346-9843

Journal article

Robinson O, Hyam MC, Karaman I, Pinto RC, Fiorito G, Gao H, Heard A, Jarvelin M-R, Lewis M, Pazoki R, Polidoro S, Tzoulaki I, Wielscher M, Elliott P, Vineis Pet al., 2018, Determinants of accelerated metabolomic and epigenetic ageing in a UK cohort, Publisher: Cold Spring Harbor Laboratory

<jats:title>Abstract</jats:title><jats:p>Markers of biological ageing have potential utility in primary care and public health. We developed an elastic net regression model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry in urine and serum (almost 100,000 features assayed), within a large sample (N=2,239) from the UK occupational Airwave cohort. We investigated the determinants of accelerated ageing, including genetic, lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (r=0.85 in independent test set). Increased metabolomic age acceleration (mAA) was associated (p&lt;0.0025) with overweight/obesity and depression and nominally associated (p&lt;0.05) with high alcohol use and low income. DNA methylation age acceleration (N=1,102) was nominally associated (p&lt;0.05) with high alcohol use, anxiety and post-traumatic stress disorder, but not correlated with mAA. Biological age acceleration may present an important mechanism linking psycho-social stress to age-related disease.</jats:p>

Working paper

Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, Ntritsos G, Dimou N, Cabrera CP, Karaman I, Fu LN, Evangelou M, Witkowska K, Tzanis E, Hellwege JN, Giri A, Edwards DRV, Sun YV, Cho K, Gaziano JM, Wilson PWF, Tsao PS, Kovesdy CP, Esko T, Magi R, Milani L, Almgren P, Boutin T, Debette S, Ding J, Giulianini F, Holliday EG, Jackson AU, Li-Gao R, Lin W-Y, Luan J, Mangino M, Oldmeadow C, Prins BP, Qian Y, Sargurupremraj M, Shah N, Surendran P, Theriault S, Verweij N, Willems SM, Zhao J-H, Amouyel P, Connell J, de Mutsert R, Doney ASF, Farrall M, Menni C, Morris AD, Noordam R, Pare G, Poulter NR, Shields DC, Stanton A, Thom S, Abecasis G, Amin N, Arking DE, Ayers KL, Barbieri CM, Batini C, Bis JC, Blake T, Bochud M, Boehnke M, Boerwinkle E, Boomsma DI, Bottinger EP, Braund PS, Brumat M, Campbell A, Campbell H, Chakravarti A, Chambers JC, Chauhan G, Ciullo M, Cocca M, Collins F, Cordell HJ, Davies G, de Borst MH, de Geus EJ, Deary IJ, Deelen J, Del Greco FM, Demirkale CY, Dorr M, Ehret GB, Elosua R, Enroth S, Erzurumluoglu AM, Ferreira T, Franberg M, Franco OH, Gandin I, Gasparini P, Giedraitis V, Gieger C, Girotto G, Goel A, Gow AJ, Gudnason V, Guo X, Gyllensten U, Hamsten A, Harris TB, Harris SE, Hartman CA, Havulinna AS, Hicks AA, Hofer E, Hofman A, Hottenga J-J, Huffman JE, Hwang S-J, Ingelsson E, James A, Jansen R, Jarvelin M-R, Joehanes R, Johansson A, Johnson AD, Joshi PK, Jousilahti P, Jukema JW, Jula A, Kahonen M, Kathiresan S, Keavney BD, Khaw K-T, Knekt P, Knight J, Kolcic I, Kooner JS, Koskinen S, Kristiansson K, Kutalik Z, Laan M, Larson M, Launer LJ, Lehne B, Lehtimaki T, Liewald DCM, Lin L, Lind L, Lindgren CM, Liu Y, Loos RJF, Lopez LM, Lu Y, Lyytikainen L-P, Mahajan A, Mamasoula C, Marrugat J, Marten J, Milaneschi Y, Morgan A, Morris AP, Morrison AC, Munson PJ, Nalls MA, Nandakumar P, Nelson CP, Niiranen T, Nolte IM, Nutile T, Oldehinkel AJ, Oostra BA, O'Reilly PF, Org E, Padmanabhan S, Palmas W, Palotie A, Pattie A, Penninx BWJH, Perolet al., 2018, Genetic analysis of over one million people identifies 535 new loci associated with blood pressure traits, Nature Genetics, Vol: 50, Pages: 1412-1425, ISSN: 1061-4036

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

Journal article

Tzoulaki I, Iliou A, Mikros E, Elliott Pet al., 2018, An overview of metabolic phenotyping in blood pressure research, Current Hypertension Reports, Vol: 20, ISSN: 1522-6417

Purpose of the ReviewThis review presents the analytical techniques, processing and analytical steps used in metabolomics phenotyping studies, as well as the main results from epidemiological studies on the associations between metabolites and high blood pressure.Recent FindingsA variety of metabolomic approaches have been applied to a range of epidemiological studies to uncover the pathophysiology of high blood pressure. Several pathways have been suggested in relation to blood pressure including the possible role of the gut microflora, inflammatory, oxidative stress, and lipid pathways. Metabolic changes have also been identified associated with blood pressure lowering effects of diets high in fruits and vegetables and low in meat intake. However, the current body of literature on metabolic profiling and blood pressure is still in its infancy, not fully consistent and requires careful interpretation.SummaryMetabolic phenotyping is a promising approach to uncover metabolic pathways associated with high blood pressure and throw light into the complex pathophysiology of hypertension.

Journal article

Wark PA, Hardie LJ, Frost GS, Alwan NA, Carter M, Elliott P, Ford HE, Hancock N, Morris MA, Mulla UZ, Noorwali EA, Petropoulou K, Murphy D, Potter GDM, Riboli E, Greenwood DC, Cade JEet al., 2018, Validity of an online 24-h recall tool (myfood24) for dietary assessment in population studies: comparison with biomarkers and standard interviews, BMC Medicine, Vol: 16, ISSN: 1741-7015

BackgroundOnline dietary assessment tools can reduce administrative costs and facilitate repeated dietary assessment during follow-up in large-scale studies. However, information on bias due to measurement error of such tools is limited. We developed an online 24-h recall (myfood24) and compared its performance with a traditional interviewer-administered multiple-pass 24-h recall, assessing both against biomarkers.MethodsMetabolically stable adults were recruited and completed the new online dietary recall, an interviewer-based multiple pass recall and a suite of reference measures. Longer-term dietary intake was estimated from up to 3 × 24-h recalls taken 2 weeks apart. Estimated intakes of protein, potassium and sodium were compared with urinary biomarker concentrations. Estimated total sugar intake was compared with a predictive biomarker and estimated energy intake compared with energy expenditure measured by accelerometry and calorimetry. Nutrient intakes were also compared to those derived from an interviewer-administered multiple-pass 24-h recall.ResultsBiomarker samples were received from 212 participants on at least one occasion. Both self-reported dietary assessment tools led to attenuation compared to biomarkers. The online tools resulted in attenuation factors of around 0.2–0.3 and partial correlation coefficients, reflecting ranking intakes, of approximately 0.3–0.4. This was broadly similar to the more administratively burdensome interviewer-based tool. Other nutrient estimates derived from myfood24 were around 10–20% lower than those from the interviewer-based tool, with wide limits of agreement. Intraclass correlation coefficients were approximately 0.4–0.5, indicating consistent moderate agreement.ConclusionsOur findings show that, whilst results from both measures of self-reported diet are attenuated compared to biomarker measures, the myfood24 online 24-h recall is comparable to the more time-consuming a

Journal article

Wark P, Frost G, Elliott P, Ford HE, Riboli E, Hardie LJ, Alwan NA, Carter M, Hancock N, Morris M, Mulla UZ, Noorwali EA, Petropoulou K, Murphy D, Potter GDM, Greenwood DC, Cade JEet al., 2018, An online 24-hour recall tool (myfood24) is valid for dietary assessment in population studies: comparison with biomarkers and standard interviews., BMC Medicine, Vol: 16, ISSN: 1741-7015

BackgroundOnline dietary assessment tools can reduce administrative costs and facilitate repeated dietary assessment during follow-up in large-scale studies. However, information on bias due to measurement error of such tools is limited. We developed an online 24-h recall (myfood24) and compared its performance with a traditional interviewer-administered multiple-pass 24-h recall, assessing both against biomarkers.MethodsMetabolically stable adults were recruited and completed the new online dietary recall, an interviewer-based multiple pass recall and a suite of reference measures. Longer-term dietary intake was estimated from up to 3 × 24-h recalls taken 2 weeks apart. Estimated intakes of protein, potassium and sodium were compared with urinary biomarker concentrations. Estimated total sugar intake was compared with a predictive biomarker and estimated energy intake compared with energy expenditure measured by accelerometry and calorimetry. Nutrient intakes were also compared to those derived from an interviewer-administered multiple-pass 24-h recall.ResultsBiomarker samples were received from 212 participants on at least one occasion. Both self-reported dietary assessment tools led to attenuation compared to biomarkers. The online tools resulted in attenuation factors of around 0.2–0.3 and partial correlation coefficients, reflecting ranking intakes, of approximately 0.3–0.4. This was broadly similar to the more administratively burdensome interviewer-based tool. Other nutrient estimates derived from myfood24 were around 10–20% lower than those from the interviewer-based tool, with wide limits of agreement. Intraclass correlation coefficients were approximately 0.4–0.5, indicating consistent moderate agreement.ConclusionsOur findings show that, whilst results from both measures of self-reported diet are attenuated compared to biomarker measures, the myfood24 online 24-h recall is comparable to the more time-consuming a

Journal article

Daniels SI, Chambers JC, Sanchez SS, La Merrill MA, Hubbard AE, Macherone A, McMullin M, Zhang L, Elliott P, Smith MT, Kooner Jet al., 2018, Elevated levels of organochlorine pesticides in South Asian immigrants are associated with an increased risk of diabetes, Journal of the Endocrine Society, Vol: 2, Pages: 832-841, ISSN: 2472-1972

ObjectiveRates of diabetes mellitus are higher in South Asians than in other populations and persist after migration. One unexplored cause may be higher exposure to persistent organic pollutants associated with diabetes in other populations. We compared organochlorine (OC) pesticide concentrations in South Asian immigrants and European whites to determine whether the disease was positively associated with OC pesticides in South Asians.Research Design and MethodsSouth Asians of Tamil or Telugu descent (n = 120) and European whites (n = 72) were recruited into the London Life Sciences Population Study cohort. Blood samples as well as biometric, clinical, and survey data were collected. Plasma levels of p,p′-dichlorodiphenyldichloroethylene (DDE), p,p′- dichlorodiphenyltrichloroethane, β-hexachlorohexane (HCH), and polychlorinated biphenyl-118 were analyzed by gas chromatography-mass spectrometry. South Asian cases and controls were categorized by binary exposure (above vs below the 50th percentile) to perform logistic regression.ResultsTamils had approximately threefold to ninefold higher levels of OC pesticides, and Telugus had ninefold to 30-fold higher levels compared with European whites. The odds of exposure to p,p′-DDE above the 50th percentile was significantly greater in South Asian diabetes cases than in controls (OR: 7.00; 95% CI: 2.22, 22.06). The odds of exposure to β-HCH above the 50th percentile was significantly greater in the Tamil cases than in controls (OR: 9.35; 95% CI: 2.43, 35.97).ConclusionsSouth Asian immigrants have a higher body burden of OC pesticides than European whites. Diabetes mellitus is associated with higher p,p′-DDE and β-HCH concentrations in this population. Additional longitudinal studies of South Asian populations should be performed.

Journal article

Justice AE, Karaderi T, Highland HM, Young KL, Graff M, Lu Y, Turcot V, Auer PL, Fine RS, Guo X, Schurmann C, Lempradl A, Marouli E, Mahajan A, Winkler TW, Locke AE, Medina-Gomez C, Esko T, Vedantam S, Giri A, Lo KS, Alfred T, Mudgal P, Ng MCY, Heard-Costa NL, Feitosa MF, Manning AK, Willems SM, Sivapalaratnam S, Abecasis G, Alam DS, Allison M, Amouyel P, Arzumanyan Z, Balkau B, Bastarache L, Bergmann S, Bielak LF, Blüher M, Boehnke M, Boeing H, Boerwinkle E, Boger CA, Bork-Jensen J, Bottinger EP, Bowden DW, Brandslund I, Broer L, Burt AA, Butterworth AS, Caulfield MJ, Cesana G, Chambers JC, Chasman DI, Chen Y-DI, Chowdhury R, Christensen C, Chu AY, Collins FS, Cook JP, Cox AJ, Crosslin DS, Danesh J, de Bakker PIW, de Denus S, de Mutsert R, Dedoussis G, Demerath EW, Dennis JG, Denny JC, Di Angelantonio E, Dorr M, Drenos F, Dube M-P, Dunning AM, Easton DF, Elliott P, Evangelou E, Farmaki A-E, Feng S, Ferrannini E, Ferrieres J, Florez JC, Fornage M, Fox CS, Franks PW, Friedrich N, Gan W, Gandin I, Gasparini P, Giedraitis V, Girotto G, Gorski M, Grallert H, Grarup N, Grove ML, Gustafsson S, Haessler J, Hansen T, Hattersley AT, Hayward C, Heid IM, Holmen OL, Hovingh GK, Howson JMM, Hu Y, Hung Y-J, Hveem K, Ikram MA, Ingelsson E, Jackson AU, Jarvik GP, Jia Y, Jørgensen T, Jousilahti P, Justesen JM, Kahali B, Karaleftheri M, Kardia SLR, Karpe F, Kee F, Kitajima H, Komulainen P, Kooner JS, Kovacs P, Kramer BK, Kuulasmaa K, Kuusisto J, Laakso M, Lakka TA, Lamparter D, Lange LA, Langenberg C, Larson EB, Lee NR, Lee W-J, Lehtimäki T, Lewis CE, Li H, Li J, Li-Gao R, Lin L-A, Lin X, Lind L, Lindström J, Linneberg A, Liu C-T, Liu DJ, Luan J, Lyytikäinen L-P, MacGregor S, Mägi R, Männistö S, Marenne G, Marten J, Masca NGD, McCarthy MI, Meidtner K, Mihailov E, Moilanen L, Moitry M, Mook-Kanamori DO, Morgan A, Morris AP, Muller-Nurasyid M, Munroe PB, Narisu N, Nelson CP, Neville M, Ntalla I, OConnel JR, Owen KR, Pedersen O, Peloso GM, Pennell CE, Perola M, Perry JA, Perry JRB, Peret al., 2018, Protein-Coding Variants Implicate Novel Genes Related to Lipid Homeostasis Contributing to Body Fat Distribution, Publisher: Cold Spring Harbor Laboratory

<jats:title>ABSTRACT</jats:title><jats:p>Body fat distribution is a heritable risk factor for a range of adverse health consequences, including hyperlipidemia and type 2 diabetes. To identify protein-coding variants associated with body fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, we analyzed 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries for discovery and 132,177 independent European-ancestry individuals for validation. We identified 15 common (minor allele frequency, MAF≥5%) and 9 low frequency or rare (MAF&lt;5%) coding variants that have not been reported previously. Pathway/gene set enrichment analyses of all associated variants highlight lipid particle, adiponectin level, abnormal white adipose tissue physiology, and bone development and morphology as processes affecting fat distribution and body shape. Furthermore, the cross-trait associations and the analyses of variant and gene function highlight a strong connection to lipids, cardiovascular traits, and type 2 diabetes. In functional follow-up analyses, specifically in <jats:italic>Drosophila</jats:italic> RNAi-knockdown crosses, we observed a significant increase in the total body triglyceride levels for two genes (<jats:italic>DNAH10</jats:italic> and <jats:italic>PLXND1</jats:italic>). By examining variants often poorly tagged or entirely missed by genome-wide association studies, we implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.</jats:p>

Working paper

Warren HR, Evangelou E, Mosen D, Mifsud B, Pazoki R, Gao H, Ntritsos G, Dimou N, Evangelou M, Hellwege J, Giri A, Esko T, Metspalu A, Tzoulaki I, Barnes MR, Wain LV, Elliott P, Caulfield MJet al., 2018, GENETIC ANALYSIS OF OVER ONE MILLION PEOPLE IDENTIFIES 535 NOVEL LOCI ASSOCIATED WITH BLOOD PRESSURE AND RISK OF CARDIOVASCULAR DISEASE, 28th European Meeting of Hypertension and Cardiovascular Protection of the European-Society-of-Hypertension (ESH), Publisher: LIPPINCOTT WILLIAMS & WILKINS, Pages: E229-E229, ISSN: 0263-6352

Conference paper

Feitosa M, Kraja A, Zhang W, Evangelou E, Gao H, Scott W, Sever P, Chambers J, Froguel P, Scott J, Elliott P, Levy Det al., 2018, Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570,000 individuals across multiple ancestries, PLoS ONE, Vol: 13, ISSN: 1932-6203

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Journal article

Zhou B, Bentham J, Di Cesare M, Bixby HRH, Danaei G, Hajifathalian K, Taddei C, Carrillo-Larco R, Khatibzadeh S, Lugero C, Peykari N, Zhang WZ, Bennett J, Bilano V, Stevens G, Riley L, Cowan M, Chen Z, Hambleton I, Jackson RT, Kengne A-P, Khang Y-H, Laxmaiah A, Liu J, Malekzadeh R, Neuhauser H, Soric M, Starc G, Sundstrom J, Woodward M, Ezzati Met al., 2018, Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: a pooled analysis of 1,018 population-based measurement studies with 88.6 million participants, International Journal of Epidemiology, Vol: 47, Pages: 872-883i, ISSN: 1464-3685

BackgroundChange in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure.MethodsWe pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20–29 years to 70–79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probit-transformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure.ResultsIn 2005–16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the high-income Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association.ConclusionsChange in mean bloo

Journal article

Davies G, Lam M, Harris SE, Trampush JW, Luciano M, Hill WD, Hagenaars SP, Ritchie SJ, Marioni RE, Fawns-Ritchie C, Liewald DCM, Okely JA, Ahola-Olli AV, Barnes CLK, Bertram L, Bis JC, Burdick KE, Christoforou A, DeRosse P, Djurovic S, Espeseth T, Giakoumaki S, Giddaluru S, Gustavson DE, Hayward C, Hofer E, Ikram MA, Karlsson R, Knowles E, Lahti J, Leber M, Li S, Mather KA, Melle I, Morris D, Oldmeadow C, Palviainen T, Payton A, Pazoki R, Petrovic K, Reynolds CA, Sargurupremraj M, Scholz M, Smith JA, Smith AV, Terzikhan N, Thalamuthu A, Trompet S, van der Lee SJ, Ware EB, Windham BG, Wright MJ, Yang J, Yu J, Ames D, Amin N, Amouyel P, Andreassen OA, Armstrong NJ, Assareh AA, Attia JR, Attix D, Avramopoulos D, Bennett DA, Boehmer AC, Boyle PA, Brodaty H, Campbell H, Cannon TD, Cirulli ET, Congdon E, Conley ED, Corley J, Cox SR, Dale AM, Dehghan A, Dick D, Dickinson D, Eriksson JG, Evangelou E, Faul JD, Ford I, Freimer NA, Gao H, Giegling I, Gillespie NA, Gordon SD, Gottesman RF, Griswold ME, Gudnason V, Harris TB, Hartmann AM, Hatzimanolis A, Heiss G, Holliday EG, Joshi PK, Kahonen M, Kardia SLR, Karlsson I, Kleineidam L, Knopman DS, Kochan NA, Konte B, Kwok JB, Le Hellard S, Lee T, Lehtimaki T, Li S-C, Liu T, Koini M, London E, Longstreth WT, Lopez OL, Loukola A, Luck T, Lundervold AJ, Lundquist A, Lyytikainen L-P, Martin NG, Montgomery GW, Murray AD, Need AC, Noordam R, Nyberg L, Ollier W, Papenberg G, Pattie A, Polasek O, Poldrack RA, Psaty BM, Reppermund S, Riedel-Heller SG, Rose RJ, Rotter JI, Roussos P, Rovio SP, Saba Y, Sabb FW, Sachdev PS, Satizabal CL, Schmid M, Scott RJ, Scult MA, Simino J, Slagboom PE, Smyrnis N, Soumare A, Stefanis NC, Stott DJ, Straub RE, Sundet K, Taylor AM, Taylor KD, Tzoulaki I, Tzourio C, Uitterlinden A, Vitart V, Voineskos AN, Kaprio J, Wagner M, Wagner H, Weinhold L, Wen KH, Widen E, Yang Q, Zhao W, Adams HHH, Arking DE, Bilder RM, Bitsios P, Boerwinkle E, Chiba-Falek O, Corvin A, De Jager PL, Debette S, Donohoe G, Elliott P, Fitzpet al., 2018, Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function, Nature Communications, Vol: 9, ISSN: 2041-1723

General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16–102) and find 148 genome-wide significant independent loci (P < 5 × 10−8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.

Journal article

Campanella G, Gunter MJ, Polidoro S, Krogh V, Palli D, Panico S, Sacerdote C, Tumino R, Fiorito G, Guarrera S, Iacoviello L, Bergdahl IA, Melin B, Lenner P, de Kok TMCM, Georgiadis P, Kleinjans JCS, Kyrtopoulos SA, Bueno-de-Mesquita HB, Lillycrop KA, May AM, Onland-Moret NC, Murray R, Riboli E, Verschuren M, Lund E, Mode N, Sandanger TM, Fiano V, Trevisan M, Matullo G, Froguel P, Elliott P, Vineis P, Chadeau-Hyam Met al., 2018, Epigenome-wide association study of adiposity and future risk of obesity-related diseases, INTERNATIONAL JOURNAL OF OBESITY, Vol: 42, Pages: 2022-2035, ISSN: 0307-0565

Journal article

Castagne R, Gares V, Karimi M, Chadeau-Hyam M, Vineis P, Delpierre C, Kelly-Irving Met al., 2018, Allostatic load and subsequent all-cause mortality: which biological markers drive the relationship? Findings from a UK birth cohort, European Journal of Epidemiology, Vol: 33, Pages: 441-458, ISSN: 0393-2990

The concept of allostatic load (AL) refers to the idea of a global physiological ‘wear and tear’ resulting from the adaptationto the environment through the stress response systems over the life span. The link between socioeconomic position (SEP)and mortality has now been established, and there is evidence that AL may capture the link between SEP and mortality. Inorder to quantitatively assess the role of AL on mortality, we use data from the 1958 British birth cohort including elevenyear mortality in 8,113 adults. Specifically, we interrogate the hypothesis of a cumulative biological risk (allostatic load)reflecting 4 physiological systems potentially predicting future risk of death (N = 132). AL was defined using 14biomarkers assayed in blood from a biosample collected at 44 years of age. Cox proportional hazard regression analysisrevealed that higher allostatic load at 44 years old was a significant predictor of mortality 11 years later [HR = 3.56 (2.3 to5.53)]. We found that this relationship was not solely related to early-life SEP, adverse childhood experiences and youngadulthood health status, behaviours and SEP [HR = 2.57 (1.59 to 4.15)]. Regarding the ability of each physiologicalsystem and biomarkers to predict future death, our results suggest that the cumulative measure was advantageous comparedto evaluating each physiological system sub-score and biomarker separately. Our findings add some evidence of a biologicalembodiment in response to stress which ultimately affects mortality.

Journal article

Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, Guo X, Hendricks AE, Karaderi T, Lempradl A, Locke AE, Mahajan A, Marouli E, Sivapalaratnam S, Young KL, Alfred T, Feitosa MF, Masca NGD, Manning AK, Medina-Gomez C, Mudgal P, Ng MCY, Reiner AP, Vedantam S, Willems SM, Winkler TW, Abecasis G, Aben KK, Alam DS, Alharthi SE, Allison M, Amouyel P, Asselbergs FW, Auer PL, Balkau B, Bang LE, Barroso I, Bastarache L, Benn M, Bergmann S, Bielak LF, Bluher M, Boehnke M, Boeing H, Boerwinkle E, Boger CA, Bork-Jensen J, Bots ML, Bottinger EP, Bowden DW, Brandslund I, Breen G, Brilliant MH, Broer L, Brumat M, Burt AA, Butterworth AS, Campbell PT, Cappellani S, Carey DJ, Catamo E, Caulfield MJ, Chambers JC, Chasman DI, Chen Y-DI, Chowdhury R, Christensen C, Chu AY, Cocca M, Collins FS, Cook JP, Corley J, Galbany JC, Cox AJ, Crosslin DS, Cuellar-Partida G, D'Eustacchio A, Danesh J, Davies G, Bakker PIW, Groot MCH, Mutsert R, Deary IJ, Dedoussis G, Demerath EW, Heijer M, Hollander AI, Ruijter HM, Dennis JG, Denny JC, Di Angelantonio E, Drenos F, Du M, Dube M-P, Dunning AM, Easton DF, Edwards TL, Ellinghaus D, Ellinor PT, Elliott P, Evangelou E, Farmaki A-E, Farooqi IS, Faul JD, Fauser S, Feng S, Ferrannini E, Ferrieres J, Florez JC, Ford I, Fornage M, Franco OH, Franke A, Franks PW, Friedrich N, Frikke-Schmidt R, Galesloot TE, Gan W, Gandin I, Gasparini P, Gibson J, Giedraitis V, Gjesing AP, Gordon-Larsen P, Gorski M, Grabe H-J, Grant SFA, Grarup N, Griffiths HL, Grove ML, Gudnason V, Gustafsson S, Haessler J, Hakonarson H, Hammerschlag AR, Hansen T, Harris KM, Harris TB, Hattersley AT, Have CT, Hayward C, He L, Heard-Costa NL, Heath AC, Heid IM, Helgeland O, Hernesniemi J, Hewitt AW, Holmen OL, Hovingh GK, Howson JMM, Hu Y, Huang PL, Huffman JE, Ikram MA, Ingelsson E, Jackson AU, Jansson J-H, Jarvik GP, Jensen GB, Jia Y, Johansson S, Jorgensen ME, Jorgensen T, Jukema JW, Kahali B, Kahn RS, Kahonen M, Kamstrup PR, Kanoni S, Kapriet al., 2018, Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 26, 2018), Nature Genetics, Vol: 50, Pages: 766-767, ISSN: 1061-4036

Journal article

Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, Guo X, Hendricks AE, Karaderi T, Lempradl A, Locke AE, Mahajan A, Marouli E, Sivapalaratnam S, Young KL, Alfred T, Feitosa MF, Masca NGD, Manning AK, Medina-Gomez C, Mudgal P, Ng MCY, Reiner AP, Vedantam S, Willems SM, Winkler TW, Abecasis G, Aben KK, Alam DS, Alharthi SE, Allison M, Amouyel P, Asselbergs FW, Auer PL, Balkau B, Bang LE, Barroso I, Bastarache L, Benn M, Bergmann S, Bielak LF, Bluher M, Boehnke M, Boeing H, Boerwinkle E, Boger CA, Bork-Jensen J, Bots ML, Bottinger EP, Bowden DW, Brandslund I, Breen G, Brilliant MH, Broer L, Brumat M, Burt AA, Butterworth AS, Campbell PT, Cappellani S, Carey DJ, Catamo E, Caulfield MJ, Chambers JC, Chasman DI, Chen Y-DI, Chowdhury R, Christensen C, Chu AY, Cocca M, Collins FS, Cook JP, Corley J, Galbany JC, Cox AJ, Crosslin DS, Cuellar-Partida G, D'Eustacchio A, Danesh J, Davies G, Bakker PIW, Groot MCH, Mutsert R, Deary IJ, Dedoussis G, Demerath EW, Heijer M, Hollander AI, Ruijter HM, Dennis JG, Denny JC, Angelantonio E, Drenos F, Du M, Dube M-P, Dunning AM, Easton DF, Edwards TL, Ellinghaus D, Ellinor PT, Elliott P, Evangelou E, Farmaki A-E, Farooqi IS, Faul JD, Fauser S, Feng S, Ferrannini E, Ferrieres J, Florez JC, Ford I, Fornage M, Franco OH, Franke A, Franks PW, Friedrich N, Frikke-Schmidt R, Galesloot TE, Gan W, Gandin I, Gasparini P, Gibson J, Giedraitis V, Gjesing AP, Gordon-Larsen P, Gorski M, Grabe H-J, Grant SFA, Grarup N, Griffiths HL, Grove ML, Gudnason V, Gustafsson S, Haessler J, Hakonarson H, Hammerschlag AR, Hansen T, Harris KM, Harris TB, Hattersley AT, Have CT, Hayward C, He L, Heard-Costa NL, Heath AC, Heid IM, Helgeland O, Hernesniemi J, Hewitt AW, Holmen OL, Hovingh GK, Howson JMM, Hu Y, Huang PL, Huffman JE, Ikram MA, Ingelsson E, Jackson AU, Jansson J-H, Jarvik GP, Jensen GB, Jia Y, Johansson S, Jorgensen ME, Jorgensen T, Jukema JW, Kahali B, Kahn RS, Kahonen M, Kamstrup PR, Kanoni S, Kaprio Jet al., 2018, Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017), NATURE GENETICS, Vol: 50, Pages: 765-766, ISSN: 1061-4036

Journal article

Aljuraiban G, Stamler J, Chan Q, van Horn L, Daviglus M, Elliott P, Oude Griep Let al., Relations between dairy product intake and blood pressure: the INTERMAP study, Journal of Hypertension, ISSN: 0263-6352

Background: epidemiologic evidence suggests that low-fat dairy consumption may lower risk of hypertension. Dairy products may be distinctly linked to health, due to differences in nutritional composition, but little is known about specific nutrients that contribute to the dairy-blood pressure (BP) association, nor to underlying kidney function. Methods: we examined cross-sectional associations to BP of dairy product intakes, total and by type, from the INTERnational study on MAcro/micronutrients and blood Pressure (INTERMAP) including 2,694 participants aged 40-59 years from the United Kingdom and the United States. Eight BP, four 24-hour dietary recalls and two 24-hour urine samples were collected during four visits. Linear regression models adjusted for lifestyle/dietary factors to estimate BP differences per 2SD higher intakes of total-and-individual-types of dairy were calculated.Results: multivariable linear regression coefficients were estimated and pooled. In contrast to total and whole-fat dairy, each 195 g/1000 kcal (2SD) greater low-fat dairy intake was associated with a lower systolic BP (SBP) -2.31 mmHg and diastolic BP (DBP) -2.27 mmHg. Significant associations attenuated with adjustment for dietary phosphorus, calcium, and lactose, but strengthened with urinary calcium adjustment. Stratification by median albumin-creatinine-ratio (ACR), (high ACR indicates impaired kidney function) showed strong associations between low-fat dairy and BP in participants with low ACR (SBP: -3.66; DBP: -2.15 mmHg), with no association in participants with high ACR. Conclusions: low-fat dairy consumption was associated with lower BP, especially among participants with low ACR. Dairy-rich nutrients including phosphorus and calcium may have contributed to the beneficial associations with BP.

Journal article

Eriksen R, Gibson R, Lamb K, McMeel Y, Vergnuad A-C, Aresu M, Spear J, Chan Q, Elliott P, Frost Get al., 2018, Nutrient profiling and adherence to components of the UK national dietary guidelines association with metabolic risk factors for cardiovascular diseases and diabetes: Airwave Health Monitoring Study, British Journal of Nutrition, Vol: 119, Pages: 695-705, ISSN: 1475-2662

CVD is the leading cause of death worldwide. Diet is a key modifiable component in the development of CVD. No official UK diet quality index exists for use in UK nutritional epidemiological studies. The aims of this study are to: (i) develop a diet quality index based on components of UK dietary reference values (DRV) and (ii) determine the association between the index, the existing UK nutrient profile (NP) model and a comprehensive range of cardiometabolic risk markers among a British adult population. A cross-sectional analysis was conducted using data from the Airwave Health Monitoring Study (n 5848). Dietary intake was measured by 7-d food diary and metabolic risk using waist circumference, BMI, blood lipid profile, glycated Hb (HbA1c) and blood pressure measurements. Diet quality was assessed using the novel DRV index and NP model. Associations between diet and cardiometabolic risk were analysed via multivariate linear models and logistic regression. A two-point increase in NP score was associated with total cholesterol (β −0·33 mmol/l, P<0·0001) and HbA1c (β −0·01 %, P<0·0001). A two-point increase in DRV score was associated with waist circumference (β −0·56 cm, P<0·0001), BMI (β −0·15 kg/m2, P<0·0001), total cholesterol (β −0·06 mmol/l, P<0·0001) and HbA1c (β −0·02 %, P=0·002). A one-point increase in DRV score was associated with type 2 diabetes (T2D) (OR 0·94, P=0·01) and obesity (OR 0·95, P<0·0001). The DRV index is associated with overall diet quality and risk factors for CVD and T2D, supporting its application in nutritional epidemiological studies investigating CVD risk in a UK population.

Journal article

Xie W, Zheng F, Evangelou E, Liu O, Yang Z, Chan Q, Elliott P, Wu Yet al., 2018, Blood pressure-lowering drugs and secondary prevention of cardiovascular disease: systematic review and meta-analysis., Journal of Hypertension, Vol: 36, Pages: 1256-1265, ISSN: 0263-6352

OBJECTIVE: To systematically evaluate the efficacy of five commonly used blood pressure-lowering drugs in reducing cardiovascular events among patients with nonacute cardiovascular disease, but without heart failure. METHODS: We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials on 18 March 2017. The primary outcome was fatal and nonfatal cardiovascular events, and the secondary outcomes were all-cause death, fatal and nonfatal myocardial infarction, and stroke. Pooled risk ratios and corresponding 95% confidence intervals (CIs) were calculated using Mantel-Haenszel random-effects meta-analyses. RESULTS: Twenty-seven randomized controlled trials with 143 095 participants and a treatment duration of at least 12 months were included in our analyses. Fifteen trials enrolled patients with coronary artery disease, eight enrolled patients with cerebral artery disease, and four enrolled patients with cardiovascular disease. Of the 27 trials, 10 trials only included hypertensive patients. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs) (risk ratio 0.85, 95% CI 0.78-0.92), angiotensin receptor blockers (risk ratio 0.92, 95% CI 0.87-0.98), and diuretics (risk ratio 0.77, 95% CI 0.66-0.90) significantly reduced the risk of cardiovascular events. Apart from this, ACEIs significantly reduced all secondary outcomes, calcium channel blockers, and diuretics reduced stroke significantly. No significant difference was found in head-to-head comparisons of each given drug class with any other class. CONCLUSIONS: Although only ACEIs have evidences showing its effect in reducing cardiovascular events and all secondary outcomes, head-to-head comparisons did not provide strong evidence in difference in the effects between these blood pressure-lowering drugs.

Journal article

Malik R, Kooner JS, Elliott P, Chambers J, Dichgans Met al., 2018, Multi-ancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes, Nature Genetics, Vol: 50, Pages: 524-537, ISSN: 1061-4036

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

Journal article

Stamler J, Chan Q, Daviglus M, Dyer A, van Horn L, Garside D, Miura K, Wu Y, Ueshima H, Zhao L, Elliott Pet al., 2018, Relation of dietary sodium (salt) to blood pressure and Its possible modulation by other dietary factors: the INTERMAP study, Hypertension, Vol: 71, Pages: 631-637, ISSN: 0194-911X

Available data indicate that dietary sodium (as salt) relates directly to blood pressure (BP). Most of these findings are from studies lacking dietary data; hence, it is unclear whether this sodium–BP relationship is modulated by other dietary factors. With control for multiple nondietary factors, but not body mass index, there were direct relations to BP of 24-hour urinary sodium excretion and the urinary sodium/potassium ratio among 4680 men and women 40 to 59 years of age (17 population samples in China, Japan, United Kingdom, and United States) in the INTERMAP (International Study on Macro/Micronutrients and Blood Pressure), and among its 2195 American participants, for example, 2 SD higher 24-hour urinary sodium excretion (118.7 mmol) associated with systolic BP 3.7 mm Hg higher. These sodium–BP relations persisted with control for 13 macronutrients, 12 vitamins, 7 minerals, and 18 amino acids, for both sex, older and younger, blacks, Hispanics, whites, and socioeconomic strata. With control for body mass index, sodium–BP—but not sodium/potassium–BP—relations were attenuated. Normal weight and obese participants manifested significant positive relations to BP of urinary sodium; relations were weaker for overweight people. At lower but not higher levels of 24-hour sodium excretion, potassium intake blunted the sodium–BP relation. The adverse association of dietary sodium with BP is minimally attenuated by other dietary constituents; these findings underscore the importance of reducing salt intake for the prevention and control of prehypertension and hypertension.

Journal article

Kaluarachchi M, Boulangé C, Karaman I, Lindon JC, Ebbels T, Elliott P, Tracy R, Olson NCet al., 2018, A comparison of human serum and plasma metabolites using untargeted 1H NMR spectroscopy and UPLC-MS, Metabolomics, Vol: 14, ISSN: 1573-3882

Introduction:Differences in the metabolite profiles between serum and plasma are incompletely understood.Objectives:To evaluate metabolic profile differences between serum and plasma and among plasma sample subtypes.Methods:We analyzed serum, platelet rich plasma (PRP), platelet poor plasma (PPP), and platelet free plasma (PFP), collected from 8 non-fasting apparently healthy women, using untargeted standard 1D and CPMG 1H NMR and reverse phase and hydrophilic (HILIC) UPLC-MS. Differences between metabolic profiles were evaluated using validated principal component and orthogonal partial least squares discriminant analysis.ResultsExplorative analysis showed the main source of variation among samples was due to inter-individual differences with no grouping by sample type. After correcting for inter-individual differences, lipoproteins, lipids in VLDL/LDL, lactate, glutamine, and glucose were found to discriminate serum from plasma in NMR analyses. In UPLC-MS analyses, lysophosphatidylethanolamine (lysoPE)(18:0) and lysophosphatidic acid(20:0) were higher in serum, and phosphatidylcholines (PC)(16:1/18:2, 20:3/18:0, O-20:0/22:4), lysoPC(16:0), PE(O-18:2/20:4), sphingomyelin(18:0/22:0), and linoleic acid were lower. In plasma subtype analyses, isoleucine, leucine, valine, phenylalanine, glutamate, and pyruvate were higher among PRP samples compared with PPP and PFP by NMR while lipids in VLDL/LDL, citrate, and glutamine were lower. By UPLC-MS, PE(18:0/18:2) and PC(P-16:0/20:4) were higher in PRP compared with PFP samples.Conclusions:Correction for inter-individual variation was required to detect metabolite differences between serum and plasma. Our results suggest the potential importance of inter-individual effects and sample type on the results from serum and plasma metabolic phenotyping studies.

Journal article

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