Imperial College London

ProfessorPaulElliott

Faculty of MedicineSchool of Public Health

Chair in Epidemiology and Public Health Medicine
 
 
 
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Contact

 

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

 
 
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Assistant

 

Miss Jennifer Wells +44 (0)20 7594 3328

 
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Location

 

154Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

616 results found

Giri A, Hellwege JN, Keaton JM, Park J, Qiu C, Warren HR, Torstenson ES, Kovesdy CP, Sun YV, Wilson OD, Robinson-Cohen C, Roumie CL, Chung CP, Birdwell KA, Damrauer SM, DuVall SL, Klarin D, Cho K, Wang Y, Evangelou E, Cabrera CP, Wain LV, Shrestha R, Mautz BS, Akwo EA, Sargurupremraj M, Debette S, Boehnke M, Scott LJ, Luan J, Zhao J-H, Willems SM, Theriault S, Shah N, Oldmeadow C, Almgren P, Li-Gao R, Verweij N, Boutin TS, Mangino M, Ntalla I, Feofanova E, Surendran P, Cook JP, Karthikeyan S, Lahrouchi N, Liu C, Sepulveda N, Richardson TG, Kraja A, Amouyel P, Farrall M, Poulter NR, Laakso M, Zeggini E, Sever P, Scott RA, Langenberg C, Wareham NJ, Conen D, Palmer CNA, Attia J, Chasman DI, Ridker PM, Melander O, Mook-Kanamori DO, van der Harst P, Cucca F, Schlessinger D, Hayward C, Spector TD, Jarvelin M-R, Hennig BJ, Timpson NJ, Wei W-Q, Smith JC, Xu Y, Matheny ME, Siew EE, Lindgren C, Herzig K-H, Dedoussis G, Denny JC, Psaty BM, Howson JMM, Munroe PB, Newton-Cheh C, Caulfield MJ, Elliott P, Gaziano JM, Concato J, Wilson PWF, Tsao PS, Edwards DRV, Susztak K, O'Donnell CJ, Hung AM, Edwards TLet al., 2019, Trans-ethnic association study of blood pressure determinants in over 750,000 individuals, Nature Genetics, Vol: 51, Pages: 51-62, ISSN: 1061-4036

In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.

Journal article

Ghosh RE, Freni-Sterrantino A, Douglas P, Parkes B, Fecht D, de Hoogh K, Fuller G, Gulliver J, Font A, Smith RB, Blangiardo M, Elliott P, Toledano MB, Hansell ALet al., 2019, Fetal growth, stillbirth, infant mortality and other birth outcomes near UK municipal waste incinerators; retrospective population based cohort and case-control study, Environment International, Vol: 122, Pages: 151-158, ISSN: 0160-4120

Background: Some studies have reported associations between municipal waste incinerator (MWI) exposures and adverse birth outcomes but there are few studies of modern MWIs operating to current European Union (EU) Industrial Emissions Directive standards. Methods: Associations between modelled ground-level particulate matter ≤10 μm in diameter (PM10) from MWI emissions (as a proxy for MWI emissions) within 10 km of each MWI, and selected birth and infant mortality outcomes were examined for all 22 MWIs operating in Great Britain 2003–10. We also investigated associations with proximity of residence to a MWI. Outcomes used were term birth weight, small for gestational age (SGA) at term, stillbirth, neonatal, post-neonatal and infant mortality, multiple births, sex ratio and preterm delivery sourced from national registration data from the Office for National Statistics. Analyses were adjusted for relevant confounders including year of birth, sex, season of birth, maternal age, deprivation, ethnicity and area characteristics and random effect terms were included in the models to allow for differences in baseline rates between areas and in incinerator feedstock. Results: Analyses included 1,025,064 births and 18,694 infant deaths. There was no excess risk in relation to any of the outcomes investigated during pregnancy or early life of either mean modelled MWI PM10 or proximity to an MWI. Conclusions: We found no evidence that exposure to PM10 from, or living near to, an MWI operating to current EU standards was associated with harm for any of the outcomes investigated. Results should be generalisable to other MWIs operating to similar standards.

Journal article

Okami Y, Ueshima H, Nakamura Y, Okuda N, Nakagawa H, Sakata K, Saitoh S, Okayama A, Yoshita K, Choudhury SR, Chan Q, Elliott P, Miura K, Stamler J, for the INTERMAP AND INTERLIPID Research Groupset al., 2019, The relationship of dietary cholesterol to serum low density lipoprotein cholesterol and confounding by reverse causality: the INTERLIPID study, Journal of Atherosclerosis and Thrombosis, Vol: 26, Pages: 170-182, ISSN: 1340-3478

im: The positive relationship between dietary cholesterol and serum cholesterol has been questioned by a set of recent cohort studies. This study aimed to investigate how employment status and education years relate to the association between dietary cholesterol and serum low-density lipoprotein cholesterol (LDL-C) in a Japanese population.Methods: A population-based, random sample, cross-sectional study (INTERLIPID) was performed. Among 1,145 Japanese individuals aged 40-59 years, 106 were excluded because of special diets, use of lipid-lowering drugs, hormone replacement, and missing data, leaving 1,039 individuals (533 men and 506 women). Dietary cholesterol was assessed from four 24-h dietary recalls, and LDL-C was measured enzymatically with an auto-analyzer. A standard questionnaire inquired about employment status and education years.Results: In men, a 1 standard deviation (SD) higher dietary cholesterol was associated with 3.16 mg/dL lower serum LDL-C (P=0.009; unadjusted model). After adjustment for covariates, higher serum LDL-C was estimated per 1 SD higher intake of dietary cholesterol in nonemployed men [self-employed, homemakers, farmers, fishermen, and retired employees; β=+9.08, 95% confidence interval (CI)=+0.90-+17.27] and less educated men (β=+4.46, 95% CI=-0.97-+9.90), whereas an inverse association was observed in employed men (β=-3.02, 95% CI=-5.49--0.54) and more educated men (β=-3.66, 95% CI=-6.25--1.07).Conclusions: In men who were nonemployed and less educated, a higher intake of dietary cholesterol was associated with elevated concentrations of serum LDL-C, whereas an inverse association was observed in men who were employed and more educated.

Journal article

Gao H, Aresu M, Vergnaud AC, McRobie D, Spear J, Heard A, Kongsgard HW, Singh D, Muller DC, Elliott P, Wells Jet al., 2018, Personal radio use and cancer risks among 48,158 British police officers and staff from the Airwave Health Monitoring Study, British Journal of Cancer, Vol: 120, Pages: 375-378, ISSN: 0007-0920

BackgroundRadiofrequency electromagnetic fields (RF-EMF) from mobile phones have been classified as potentially carcinogenic. No study has investigated use of Terrestrial Trunked Radio (TETRA), a source of RF-EMF with wide occupational use, and cancer risks.MethodsWe investigated association of monthly personal radio use and risk of cancer using Cox proportional hazards regression among 48,518 police officers and staff of the Airwave Health Monitoring Study in Great Britain.ResultsDuring median follow-up of 5.9 years, 716 incident cancer cases were identified. Among users, the median of the average monthly duration of use in the year prior to enrolment was 30.5  min (inter-quartile range 8.1, 68.1). Overall, there was no association between personal radio use and risk of all cancers (hazard ratio [HR] = 0.98, 95% confidence interval [CI]: 0.93, 1.03). For head and neck cancers HR = 0.72 (95% CI: 0.30, 1.70) among personal radio users vs non-users, and among users it was 1.06 (95% CI: 0.91, 1.23) per doubling of minutes of personal radio use.ConclusionsWith the limited follow-up to date, we found no evidence of association of personal radio use with cancer risk. Continued follow-up of the cohort is warranted.

Journal article

Gibson R, Lau C-H, Loo RL, Ebbles T, Chekmeneva E, Dyer A, Miura K, Ueshima H, Zhao L, Elliott P, Daviglus M, Stamler J, Van Horn L, Holmes E, Chan Qet al., 2018, American Heart Association's Epidemiology and Prevention/Lifestyle and Cardiometabolic Health 2019 Scientific Sessions, American Heart Association EpiLifestyle

Conference paper

Piel FBJ, Brandon P, Hima D, Anna L H, Paul Eet al., 2018, The challenge of opt-outs from NHS data: a small-area perspective, Journal of Public Health, Vol: 40, Pages: e594-e600, ISSN: 1741-3842

Journal article

Chadeau M, Campanella G, Gunter MJ, Polidoro S, Krogh V, Palli D, Panico S, Sacerdote C, Tumino R, Fiorito G, Guarrera S, Iacovello L, Bergdahl I, Melin B, Lenner P, de Kok T, Georgiadis P, Kleinjans J, Kyrtopoulos S, Bueno-de-Mesquita B, Lillycrop K, May A, Onland-Moret C, Murray R, Riboli E, Verschuren M, Lund E, Mode N, Sandanger TM, Fiano V, Trevisan M, Matullo G, Froguel P, Elliott P, Vineis Pet 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

BackgroundObesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.MethodsDNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.ResultsWe identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10−7), higher triglyceride levels (P = 5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10−3) and one intergenic locus on chromosome 1 was inversely associa

Journal article

Gibson R, Frost G, Chan Q, Elliott P, Singh D, Eriksen R, Heard A, Vergnaud ACet al., 2018, A cross-sectional investigation into the occupational and socio-demographic characteristics of British police force employees reporting a dietary pattern associated with cardiometabolic risk: Findings from the Airwave Health Monitoring Study, European Journal of Nutrition, Vol: 57, Pages: 2913-2926, ISSN: 0044-264X

PurposeThe aims of this study were to (1) determine the association between diet quality using the Dietary Approaches to Stop Hypertension (DASH) score and cardiometabolic risk in a British working population and (2) identify employee characteristics associated with reporting a poorer quality dietary pattern.MethodsBritish police employees enrolled (2007–2012) into the Airwave Health Monitoring Study (n = 5527) were included for sex-specific cross-sectional analyses. Dietary intakes were measured using 7-day food records. DASH score was calculated to determine diet quality. Logistic regression evaluated associations between (1) diet quality and increased cardiometabolic risk (defined as ≥ 3 risk markers: dyslipidaemia, elevated blood pressure, waist circumference, CRP or HbA1c), and (2) poor diet quality (lowest fifth of DASH score distribution) and employee characteristics.ResultsEmployees recording a poor diet quality had greater odds (OR) of increased cardiometabolic risk independent of established risk factors (demographic, lifestyle and occupational) and BMI: men OR 1.50 (95% CI 1.12–2.00), women: OR 1.84 (95% CI 1.19–2.97) compared to the healthiest diet group. Characteristics associated with reporting a poor quality diet were employment in Scotland vs. England: men OR 1.88 (95% CI 1.53–2.32), women: OR 1.49 (95% CI 1.11–2.00), longer working hours (≥ 49 vs. ≤40 h) men: OR 1.53 (95% CI 1.21–1.92) women: OR 1.53 (95% CI 1.12–2.09). For men, job strain (high vs. low) was associated with reporting a poor diet quality OR 1.66 (95% CI 1.30–2.12).ConclusionsThe general population disparities in diet quality between England and Scotland were reflected in British police employees. The association of longer working hours and job strain with diet quality supports the targeting of workplace nutritional interventions.

Journal article

Bentley AR, Evangelou E, Zhang W, Afaq S, Lehne B, Poulter N, Sever P, Chambers J, Elliott P, Froguel P, Scott J, Cupples Aet al., Multi-ancestry genome-wide smoking interaction study of 387,272 individuals identifies novel lipid loci., Nature Genetics, ISSN: 1061-4036

Serum lipids, such as triglycerides (TG) and high- and low-density lipoprotein cholesterol (HDL and LDL), are influenced by both genetic and lifestyle factors. Over 250 lipid loci have been identified,1-6 yet, it is unclear to what extent lifestyle factors modify the effects of these variants, or those yet to be identified. Smoking is associated with an unfavorable lipid profile,7,8 warranting its investigation as a lifestyle factor that potentially modifies genetic associations with lipids. Identifying interactions using traditional 1 degree of freedom (1df) tests of SNP x smoking terms may have low power, except in very large sample sizes. To enhance the detection of loci, a 2 degree of freedom (2df) test that jointly evaluates the interaction and main effects was developed.9 The Gene-Lifestyle Interactions Working Group, under the aegis of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium10, was formed to conduct analyses of lifestyle interactions in the genetic basis of cardiovascular traits. As both genetic and lifestyle factors differ across populations with different ancestry backgrounds, and to address the underrepresentation of non-European populations in genomic research, great effort went into creating a large, multi-ancestry resource for these investigations.11 Here, we report a genome-wide interaction study that uses both the 1df test of interaction and the 2df joint test of main and interaction effects to test the hypothesis that genetic associations of serum lipids differ by smoking status.

Journal article

Takeuchi F, Akiyama M, Matoba N, Katsuya T, Nakatochi M, Tabara Y, Narita A, Saw W-Y, Moon S, Spracklen CN, Chai J-F, Kim Y-J, Zhang L, Wang C, Li H, Li H, Wu J-Y, Dorajoo R, Nierenberg JL, Wang YX, He J, Bennett DA, Takahashi A, Momozawa Y, Hirata M, Matsuda K, Rakugi H, Nakashima E, Isono M, Shirota M, Hozawa A, Ichihara S, Matsubara T, Yamamoto K, Kohara K, Igase M, Han S, Gordon-Larsen P, Huang W, Lee NR, Adair LS, Hwang MY, Lee J, Chee ML, Sabanayagam C, Zhao W, Liu J, Reilly DF, Sun L, Huo S, Edwards TL, Long J, Chang L-C, Chen C-H, Yuan J-M, Koh W-P, Friedlander Y, Kelly TN, Wei WB, Xu L, Cai H, Xiang Y-B, Lin K, Clarke R, Walters RG, Millwood IY, Li L, Chambers JC, Kooner JS, Elliott P, van der Harst P, Chen Z, Sasaki M, Shu X-O, Jonas JB, He J, Heng C-K, Chen Y-T, Zheng W, Lin X, Teo Y-Y, Tai E-S, Cheng C-Y, Wong TY, Sim X, Mohlke KL, Yamamoto M, Kim B-J, Miki T, Nabika T, Yokota M, Kamatani Y, Kubo M, Kato Net al., 2018, Interethnic analyses of blood pressure loci in populations of East Asian and European descent., Nature Communications, Vol: 9, ISSN: 2041-1723

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.

Journal article

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, Publisher correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits, Nature Genetics, Vol: 50, Pages: 1755-1755, ISSN: 1061-4036

Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0205-x, published online 17 September 2018.

Journal article

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

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

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

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

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

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