Imperial College London

DrEvangelosEvangelou

Faculty of MedicineSchool of Public Health

Senior Lecturer
 
 
 
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e.evangelou

 
 
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Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
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268 results found

Adam GP, Pappas D, Papageorgiou H, Evangelou E, Trikalinos TAet al., 2022, A novel tool that allows interactive screening of PubMed citations showed promise for the semi-automation of identification of Biomedical Literature, JOURNAL OF CLINICAL EPIDEMIOLOGY, Vol: 150, Pages: 63-71, ISSN: 0895-4356

Journal article

Missiou A, Lionis C, Evangelou E, Tatsioni Aet al., 2022, Health outcomes in primary care: a 20-year evidence map of randomized controlled trials, FAMILY PRACTICE, ISSN: 0263-2136

Journal article

Said S, Pazoki R, Karhunen V, Vosa U, Ligthart S, Bodinier B, Koskeridis F, Welsh P, Alizadeh BZ, Chasman DI, Sattar N, Chadeau-Hyam M, Evangelou E, Jarvelin M-R, Elliott P, Tzoulaki I, Dehghan Aet al., 2022, Genetic analysis of over half a million people characterises C-reactive protein loci (vol 13, 2198, 2022), Nature Communications, Vol: 13, Pages: 1-1, ISSN: 2041-1723

Journal article

Sadlon A, Takousis P, Evangelou E, Prokopenko I, Alexopoulos P, Udeh-Momoh CT, Price G, Middleton L, Perneczky Ret al., 2022, A multi-omics approach identifies a blood-based miRNA signature of cognitive decline in two large observational trials

<jats:title>Abstract</jats:title><jats:p>Identifying individuals before the onset of overt symptoms is a key prerequisite for the prevention of Alzheimer’s disease (AD). A wealth of data reports dysregulated microRNA (miRNA) expression in the blood of individuals with AD, but evidence in individuals at subclinical stages is sparse. In this study, a qPCR analysis of a prioritised set of 38 candidate miRNAs in the blood of 830 healthy individuals from the CHARIOT PRO cohort (West London, UK) was undertaken. Here, we identified six differentially expressed miRNAs (hsa-miR-128-3p, hsa-miR-144-5p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-29c-3p and hsa-miR-363-3p) in the blood of individuals with low cognitive performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A pathway enrichment analysis for the six miRNAs indicated involvement of apoptosis and inflammation, relevant in early AD stages. Subsequently, we used whole genome sequencing (WGS) data from 750 individuals from the AD Neuroimaging Initiative (ADNI) to perform a genetic association analysis for polymorphisms within the significant miRNAs’ genes and CSF concentrations of phosphorylated-tau, total-tau, amyloid-β42 and soluble-TREM2 and BACE1 activity. Our analysis revealed 24 SNPs within <jats:italic>MIR29C</jats:italic> to be associated with CSF levels of amyloid-β42 and soluble-TREM2 and BACE1 activity. Our study shows the potential of a six-miRNA set as diagnostic blood biomarker of subclinical cognitive deficits in AD. Polymorphisms within <jats:italic>MIR29C</jats:italic> suggest a possible interplay between the amyloid cascade and microglial activation at preclinical stages of AD.</jats:p>

Journal article

Antonatos C, Panoutsopoulou M, Georgakilas GK, Evangelou E, Vasilopoulos Yet al., 2022, Gene Expression Meta-Analysis of Potential Shared and Unique Pathways between Autoimmune Diseases under Anti-TNFα Therapy., Genes (Basel), Vol: 13

While anti-TNFα has been established as an effective therapeutic approach for several autoimmune diseases, results from clinical trials have uncovered heterogeneous patients' response to therapy. Here, we conducted a meta-analysis on the publicly available gene expression cDNA microarray datasets that examine the differential expression observed in response to anti-TNFα therapy with psoriasis (PsO), inflammatory bowel disease (IBD) and rheumatoid arthritis (RA). Five disease-specific meta-analyses and a single combined random-effects meta-analysis were performed through the restricted maximum likelihood method. Gene Ontology and Reactome Pathways enrichment analyses were conducted, while interactions between differentially expressed genes (DEGs) were determined with the STRING database. Four IBD, three PsO and two RA datasets were identified and included in our analyses through our search criteria. Disease-specific meta-analyses detected distinct pro-inflammatory down-regulated DEGs for each disease, while pathway analyses identified common inflammatory patterns involved in the pathogenesis of each disease. Combined meta-analyses further revealed DEGs that participate in anti-inflammatory pathways, namely IL-10 signaling. Our analyses provide the framework for a transcriptomic approach in response to anti-TNFα therapy in the above diseases. Elucidation of the complex interactions involved in such multifactorial phenotypes could identify key molecular targets implicated in the pathogenesis of IBD, PsO and RA.

Journal article

Said S, Karhunen V, vosa U, ligthart S, Bodinier B, Koskeridis F, welsh P, Alizadeh B, Daniel C, sattar N, Chadeau M, evalgelou E, Jarvelin M-R, Elliott P, Tzoulaki I, Dehghan Aet al., 2022, Genetic analysis of over half a million people characterises C-reactive protein loci, Nature Communications, Vol: 13, ISSN: 2041-1723

Chronic low-grade inflammation is linked to a multitude of chronic diseases. We report the largest genome-wide association study (GWAS) on C-reactive protein (CRP), a marker of systemic inflammation, in UK Biobank participants (N = 427,367, European descent) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (total N = 575,531 European descent). We identify 266 independent loci, of which 211 are not previously reported. Gene-set analysis highlighted 42 gene sets associated with CRP levels (p ≤ 3.2 ×10−6) and tissue expression analysis indicated a strong association of CRP related genes with liver and whole blood gene expression. Phenome-wide association study identified 27 clinical outcomes associated with genetically determined CRP and subsequent Mendelian randomisation analyses supported a causal association with schizophrenia, chronic airway obstruction and prostate cancer. Our findings identified genetic loci and functional properties of chronic low-grade inflammation and provided evidence for causal associations with a range of diseases.

Journal article

Warren H, Edwards T, Vaez A, Keaton J, Kamali Z, Xie T, Ani A, Evangelou E, Hellwege J, Yengo L, Young W, Traylor M, Giri A, Visscher P, Chasman D, Morris A, Caulfield M, Hwang S-J, Kooner J, Conen D, Attia J, Morrison A, Loos R, Kristiansson K, Schmidt R, Hicks A, Pramstaller P, Nelson C, Samani N, Risch L, Gyllensten U, Melander O, Riese H, Wilson J, Campbell H, Psaty B, Lu Y, Rotter J, Guo X, Rice K, Vollenweider P, Sundstrom J, Langenberg C, Tobin M, Giedraitis V, Luan J, Tuomilehto J, Kutalik Z, Ripatti S, Salomaa V, Girotto G, Trompet S, Jukema JW, Harst PVD, Ridker P, Giulianini F, Vitart V, Goel A, Watkins H, Harris S, Deary I, Most PVD, Oldehinkel A, Keavney B, Hayward C, Campbell A, Boehnke M, Scott L, Boutin T, Mamasoula C, Jarvelin M-R, Peters A, Gieger C, Lakatta E, Cucca F, Hui J, Knekt P, Enroth S, de Borst M, Polasek O, Concas MP, Catamo E, Cocca M, Li-Gao R, Hofer E, Schmidt H, Spedicati B, Waldenberger M, Strachan D, Laan M, Teumer A, Dörr M, Gudnason V, Cook J, Ruggiero D, Kolcic I, Boerwinkle E, Traglia M, Lehtimäki T, Raitakari O, Johnson A, Newton-Cheh C, Brown M, Dominiczak A, Sever P, Poulter N, Chambers J, Elosua R, Siscovick D, Esko T, Metspalu A, Strawbridge R, Laakso M, Hamsten A, Hottenga J-J, de Geus E, Morris A, Palmer C, Nolte I, Milaneschi Y, Marten J, Wright A, Zeggini E, Howson J, O'Donnell C, Spector T, Nalls M, Simonsick E, Liu Y, Duijn CV, Butterworth A, Danesh J, Menni C, Wareham N, Khaw K, Denny J, Levy D, Munroe P, Snieder Het al., 2022, Genome-wide analysis in over 1 million individuals reveals over 2,000 independent genetic signals for blood pressure

<jats:title>Abstract</jats:title> <jats:p>Hypertension is a leading cause of premature death affecting more than a billion individuals worldwide. Here we report on the genetic determinants of blood pressure (BP) traits (systolic, diastolic, and pulse pressure) in the largest single-stage genome-wide analysis to date (N = 1,028,980 European-descent individuals). We identified 2,103 independent genetic signals (P &lt; 5x10<jats:sup>− 8</jats:sup>) for BP traits, including 113 novel loci. These associations explain ~ 40% of common SNP heritability of systolic and diastolic BP. Comparison of top versus bottom deciles of polygenic risk scores (PRS) based on these results reveal clinically meaningful differences in BP (12.9 mm Hg for systolic BP, 95% CI 11.5–14.2 mm Hg, p = 9.08×10<jats:sup>− 73</jats:sup>) and hypertension risk (OR 5.41; 95% CI 4.12 to 7.10; P = 9.71×10<jats:sup>− 33</jats:sup>) in an independent dataset. Compared with the area under the curve (AUC) for hypertension discrimination for a model with sex, age, BMI, and genetic ancestry, adding systolic and diastolic BP PRS increased discrimination from 0.791 (95% CI = 0.781–0.801) to 0.814 (95% CI = 0.805–0.824, ∆AUC = 0.023, P = 2.27x10<jats:sup>− 22</jats:sup>). Our transcriptome-wide association study detected 2,793 BP colocalized associations with genetically-predicted expression of 1,070 genes in five cardiovascular tissues, of which 500 are previously unreported for BP traits. These findings represent an advance in our understanding of hypertension and highlight the role of increasingly large genomic studies for development of more accurate PRS, which may inform precision health research.</jats:p>

Journal article

Bellou V, Tzoulaki I, van Smeden M, Moons KGM, Evangelou E, Belbasis Let al., 2022, Prognostic factors for adverse outcomes in patients with COVID-19: a field-wide systematic review and meta-analysis, European Respiratory Journal, Vol: 59, ISSN: 0903-1936

INTRODUCTION: The individual prognostic factors for COVID-19 are unclear. For this reason, we aimed to present a state-of-the-art systematic review and meta-analysis on the prognostic factors for adverse outcomes in COVID-19 patients. METHODS: We systematically reviewed PubMed from January 1, 2020 to July 26, 2020 to identify non-overlapping studies examining the association of any prognostic factor with any adverse outcome in patients with COVID-19. Random-effects meta-analysis was performed, and between-study heterogeneity was quantified using I2 metric. Presence of small-study effects was assessed by applying the Egger's regression test. RESULTS: We identified 428 eligible articles, which were used in a total of 263 meta-analyses examining the association of 91 unique prognostic factors with 11 outcomes. Angiotensin-converting enzyme inhibitors, obstructive sleep apnea, pharyngalgia, history of venous thromboembolism, sex, coronary heart disease, cancer, chronic liver disease, chronic obstructive pulmonary disease, dementia, any immunosuppressive medication, peripheral arterial disease, rheumatological disease and smoking were associated with at least one outcome and had >1000 events, p-value <0.005, I2 <50%, 95% prediction interval excluding the null value, and absence of small-study effects in the respective meta-analysis. The risk of bias assessment using the Quality In Prognosis Studies tool indicated high risk of bias in 302 of 428 articles for study participation, 389 articles for adjustment for other prognostic factors, and 396 articles for statistical analysis and reporting. CONCLUSIONS: Our findings could be used for prognostic model building and guide patients' selection for randomised clinical trials.

Journal article

Christakoudi S, Tsilidis K, Evangelou E, Riboli Eet al., 2021, Association of body-shape phenotypes with imaging measures of body composition in the UK Biobank cohort: relevance to colon cancer risk, BMC Cancer, Vol: 21, Pages: 1-15, ISSN: 1471-2407

BackgroundBody mass index (BMI), waist and hip circumference are strongly correlated and do not reflect body composition. A Body Shape Index (ABSI) and Hip Index (HI) define waist and hip size among individuals with the same weight and height and would thus reflect body density. We examined differences in body composition between body-shape phenotypes defined with ABSI and HI and used this information to propose explanations for associations between body-shape phenotypes and colon cancer risk.MethodsWe used data from the UK Biobank Resource for 15,520 men, 16,548 women with dual-emission X-ray absorptiometry (DXA) measurements; 3997 men, 4402 women with magnetic resonance imaging (MRI) measurements; 200,289 men, 230,326 women followed-up for colon cancer. We defined body-shape phenotypes as: large-ABSI-small-HI (“apple”), small-ABSI-large-HI (“pear”), small-ABSI-small-HI (“slim”), large-ABSI-large-HI (“wide”). We evaluated differences in body composition in linear models and associations with colon cancer risk in Cox proportional hazards models adjusted for confounders and explored heterogeneity by BMI.ResultsAmong individuals with the same height and weight, visceral adipose tissue (VAT) was lowest for “pear” and highest for “apple”, while abdominal subcutaneous adipose tissue (ASAT) was lowest for “slim” and highest for “wide” phenotype. In the gynoid region, differences between “apple” and “pear” phenotypes were accounted for mainly by fat mass in women but by lean mass in men. In men, lean mass was inversely associated with waist size, while the pattern of gynoid fat resembled ASAT in women. Lean and fat mass were higher for higher BMI, but not hand grip strength. Compared to normal weight “pear”, the risk of colon cancer in men (1029 cases) was higher for “apple” phenotype for normal weight (hazard ratio HR =&thi

Journal article

Koutsonida M, Kanellopoulou A, Markozannes G, Gousia S, Doumas MT, Sigounas DE, Tzovaras VT, Vakalis K, Tzoulaki I, Evangelou E, Rizos EC, Ntzani E, Aretouli E, Tsilidis KKet al., 2021, Adherence to Mediterranean diet and cognitive abilities in the Greek cohort of Epirus Health Study, Nutrients, Vol: 13, ISSN: 2072-6643

The Mediterranean diet is commonly proposed as a major modifiable protective factor that may delay cognitive impairment in the elderly. The aim of the study was to investigate the cross-sectional association of adherence to the Mediterranean diet with cognitive abilities in a younger Greek population. A total of 1201 healthy adults aged 21–77 years (mean: 47.8) from the Epirus Health Study cohort were included in the analysis. Adherence to the Mediterranean diet was measured using the 14-point Mediterranean Diet Adherence Screener (MEDAS) and cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. Statistical analysis was performed using multiple linear regression models adjusted for age, sex, education, body mass index, smoking status, alcohol consumption and physical activity. Overall, no association was found between the MEDAS score and cognitive tests, which could be explained by the young mean age and high level of education of the participants. Future studies should target young and middle-aged individuals to gain further understanding of the association between Mediterranean diet and cognition in this age group.

Journal article

Sun X, Ho JE, Gao H, Evangelou E, Yao C, Huan T, Hwang S-J, Courchesne P, Larson MG, Levy D, Ma J, Liu Cet al., 2021, Associations of Alcohol Consumption with Cardiovascular Disease-Related Proteomic Biomarkers: The Framingham Heart Study, JOURNAL OF NUTRITION, Vol: 151, Pages: 2574-2582, ISSN: 0022-3166

Journal article

Bellou V, Belbasis L, Evangelou E, 2021, Tobacco Smoking and Risk for Pulmonary Fibrosis: A Prospective Cohort Study From the UK Biobank., Chest, Vol: 160, Pages: 983-993

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease of unknown origin. A limited number of small studies show an effect of tobacco smoking on risk of IPF, but second-hand smoking has not been examined. RESEARCH QUESTION: Are smoking-related exposures associated with risk of IPF and does interaction between them exist? STUDY DESIGN AND METHODS: We designed a prospective cohort study using UK Biobank data, including 437,453 nonrelated men and women of White ethnic background (40-69 years of age at baseline). We assessed the effect of tobacco smoking-related exposures on risk for IPF using Cox regression adjusted for age, sex, Townsend deprivation index, and home area population density. We also examined potential additive and multiplicative interaction between these exposures. Multiple imputation with chained equations was used to address missing data. RESULTS: We identified 802 incident IPF cases. We showed an association between smoking status (hazard ratio [HR], 2.12; 95% CI, 1.81-2.47), and maternal smoking (HR, 1.38; 95% CI, 1.18-1.62) with risk of IPF. In ever smokers, a dose-response relationship was observed between pack-years of smoking and risk of IPF (HR per 1-pack-year increase, 1.013; 95% CI, 1.009-1.016). Furthermore, an additive and multiplicative interaction was observed between maternal smoking and smoking status, with a relative excess risk due to interaction of 1.00 (95% CI, 0.45-1.54) and a ratio of HRs of 1.50 (95% CI, 1.05-2.14). INTERPRETATION: Active and maternal tobacco smoking have an independent detrimental effect on risk of IPF and work synergistically. Also, intensity of smoking presents a dose-response association with IPF, strengthening the hypothesis for a potentially causal association.

Journal article

Tsilidis K, 2021, Prevalence and determinants of sex-specific dietary supplement use in a Greek cohort, Nutrients, Vol: 13, Pages: 1-15, ISSN: 2072-6643

We describe the profile of dietary supplement use and its correlates in the Epirus Health Study cohort, which consists of 1,237 adults (60.5% women) residing in urban north-west Greece. The association between dietary supplement use and demographic characteristics, lifestyle behaviours, personal medical history and clinical measurements was assessed using logistic regression models, separately for women and men. The overall prevalence of dietary supplement use was 31.4%, and it was higher in women (37.3%) compared to men (22.4%; p-value=4.2-08). Based on multivariable logistic regression models, dietary supplement use in women was associated with age (positively until middle-age and slightly negatively afterwards), the presence of a chronic health condition (OR=1.71; 95% CI, 1.18-2.46), lost/removed teeth (OR=0.52; 95% CI, 0.35-0.78) and diastolic blood pressure (OR per 5 mmHg increase=0.84; 95% CI, 0.73-0.96); body mass index and worse general health status were borderline inversely associated. In men, dietary supplement use was positively associated with being employed (OR=2.53; 95% CI, 1.21-5.29). A considerable proportion of our sample used dietary supplements, and the factors associated with it differed between women and men.

Journal article

Christakoudi S, Tsilidis K, Evangelou E, Riboli Eet al., 2021, A Body Shape Index (ABSI), hip index and risk of cancer in the UK Biobank cohort, Cancer Medicine, Vol: 10, Pages: 5614-5628, ISSN: 2045-7634

Abdominal size is associated positively with the risk of some cancers but the influence of body mass index (BMI) and gluteofemoral size is unclear because waist and hip circumference are strongly correlated with BMI. We examined associations of 33 cancers with A Body Shape Index (ABSI) and hip index (HI), which are independent of BMI by design, and compared these with waist and hip circumference, using multivariable Cox proportional hazards models in UK Biobank. During a mean follow up of seven years, 14,682 incident cancers were ascertained in 200,289 men and 12,965 cancers in 230,326 women. In men, ABSI was associated positively with cancers of the head and neck (hazard ratio HR=1.14; 95% confidence interval 1.03-1.26 per one standard deviation increment), oesophagus (adenocarcinoma, HR=1.27; 1.12-1.44), gastric cardia (HR=1.31; 1.07-1.61), colon (HR=1.18; 1.10-1.26), rectum (HR=1.13; 1.04-1.22), lung (adenocarcinoma, HR=1.16; 1.03-1.30; squamous-cell carcinoma (SCC), HR=1.33; 1.17-1.52), and bladder (HR=1.15; 1.04-1.27), while HI was associated inversely with cancers of the oesophagus (adenocarcinoma, HR=0.89; 0.79-1.00), gastric cardia (HR=0.79; 0.65-0.96), colon (HR=0.92; 0.86-0.98), liver (HR=0.86; 0.75-0.98), and multiple myeloma (HR=0.86; 0.75-1.00). In women, ABSI was associated positively with cancers of the head and neck (HR=1.27; 1.10-1.48), oesophagus (SCC, HR=1.37; 1.07-1.76), colon (HR=1.08; 1.01-1.16), lung (adenocarcinoma, HR=1.17; 1.06-1.29; SCC, HR=1.40; 1.20-1.63; small-cell, HR=1.39; 1.14-1.69), kidney (clear-cell, HR=1.25; 1.03-1.50), and post-menopausal endometrium (HR=1.11; 1.02-1.20), while HI was associated inversely with skin SCC (HR=0.91; 0.83-0.99), post-menopausal kidney cancer (HR=0.77; 0.67-0.88) and post-menopausal melanoma (HR=0.90; 0.83-0.98). Unusually, ABSI was associated inversely with melanoma in men (HR=0.89; 0.82-0.96) and pre-menopausal women (HR=0.77; 0.65-0.91). Waist and hip circumference reflected associations with BMI

Journal article

Janiaud P, Agarwal A, Tzoulaki I, Theodoratou E, Tsilidis KK, Evangelou E, Ioannidis JPAet al., 2021, Validity of observational evidence on putative risk and protective factors: appraisal of 3744 meta-analyses on 57 topics, BMC Medicine, Vol: 19, ISSN: 1741-7015

BACKGROUND: The validity of observational studies and their meta-analyses is contested. Here, we aimed to appraise thousands of meta-analyses of observational studies using a pre-specified set of quantitative criteria that assess the significance, amount, consistency, and bias of the evidence. We also aimed to compare results from meta-analyses of observational studies against meta-analyses of randomized controlled trials (RCTs) and Mendelian randomization (MR) studies. METHODS: We retrieved from PubMed (last update, November 19, 2020) umbrella reviews including meta-analyses of observational studies assessing putative risk or protective factors, regardless of the nature of the exposure and health outcome. We extracted information on 7 quantitative criteria that reflect the level of statistical support, the amount of data, the consistency across different studies, and hints pointing to potential bias. These criteria were level of statistical significance (pre-categorized according to 10-6, 0.001, and 0.05 p-value thresholds), sample size, statistical significance for the largest study, 95% prediction intervals, between-study heterogeneity, and the results of tests for small study effects and for excess significance. RESULTS: 3744 associations (in 57 umbrella reviews) assessed by a median number of 7 (interquartile range 4 to 11) observational studies were eligible. Most associations were statistically significant at P < 0.05 (61.1%, 2289/3744). Only 2.6% of associations had P < 10-6, ≥1000 cases (or ≥20,000 participants for continuous factors), P < 0.05 in the largest study, 95% prediction interval excluding the null, and no large between-study heterogeneity, small study effects, or excess significance. Across the 57 topics, large heterogeneity was observed in the proportion of associations fulfilling various quantitative criteria. The quantitative criteria were mostly independent from one another. Across 62 associations assessed in both RCTs and in o

Journal article

Kanellopoulou A, Koskeridis F, Markozannes G, Bouras E, Soutziou C, Chaliasos K, Doumas MT, Sigounas DE, Tzovaras VT, Panos A, Stergiou Y, Mellou K, Papamichail D, Aretouli E, Chatzidimitriou D, Chatzopoulou F, Bairaktari E, Tzoulaki I, Evangelou E, Rizos EC, Ntzani E, Vakalis K, Tsilidis Ket al., 2021, Awareness, knowledge and trust in the Greek authorities towards COVID-19 pandemic: results from the Epirus Health Study cohort, BMC Public Health, Vol: 21, ISSN: 1471-2458

Background: To assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants.Methods: The EHS is an ongoing and deeply-phenotyped prospective cohort study that has recruited 667 participants in northwest Greece until August 31st, 2020. Level of knowledge on coronavirus (SARS-CoV-2) transmission and COVID-19 severity was labeled as poor, moderate or good. Variables assessing knowledge and beliefs towards the pandemic were summarized overall and by sex, age group (25-39, 40-49, 50-59, ≥60 years) and period of report (before the lifting of lockdown measures in Greece: March 30th to May 3rd, and two post-lockdown time periods: May 4th to June 31st, July 1st to August 31st). A hypothesis generating exposure-wide association analysis was conducted to evaluate the associations between 153 agnostically-selected explanatory variables and participants’ knowledge. Correction for multiple comparisons was applied using a false discovery rate (FDR) threshold of 5%.Results: A total of 563 participants (49 years mean age; 60% women) had available information on the standard EHS questionnaire, the clinical and biochemical measurements, and the COVID-19-related questionnaire. Percentages of poor, moderate and good knowledge status regarding COVID-19 were 4.5%, 10.0% and 85.6%, respectively. The majority of participants showed absolute or moderate trust in the Greek health authorities for the management of the epidemic (90.1%), as well as in the Greek Government (84.7%) and the official national sources of information (87.4%). Trust in the authorities was weaker in younger participants and those who joined the study after the lifting of lockdown measures (p-value0.001). None of the factors examined was associated with participants’ level of knowledge after correction for multiple testing.Conclusions: High level of knowledge about the COVID-19 pandemic and t

Journal article

Evangelou E, Suzuki H, Bai W, Pazoki R, Gao H, Matthews P, Elliott Pet al., 2021, Alcohol consumption in the general population is associated with structural changes in multiple organ systems., eLife, Vol: 10, Pages: 1-15, ISSN: 2050-084X

Background:Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample.Methods:We assessed global effect sizes of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta, and liver of UK Biobank participants who reported drinking alcohol.Results:We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (–1.7 × 10−3 ± 0.76 × 10−3 per doubling of alcohol consumption, p=3.0 × 10−14). Alcohol consumption was also associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption.Conclusions:Our results imply that there is not a ‘safe threshold’ below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.

Journal article

Christakoudi S, Evangelou E, Riboli E, Tsilidis Ket al., 2021, GWAS of allometric body-shape indices in UK Biobank identifies loci suggesting associations with morphogenesis, organogenesis, adrenal cell renewal and cancer, Scientific Reports, Vol: 11, Pages: 1-18, ISSN: 2045-2322

Genetic studies have examined body-shape measures adjusted for body mass index (BMI), while allometric indices are additionally adjusted for height. We performed the first genome-wide association study of A Body Shape Index (ABSI), Hip Index (HI) and the new Waist-to-Hip Index and compared these with traditional indices, using data from the UK Biobank Resource for 219,872 women and 186,825 men with white British ancestry and Bayesian linear mixed-models (BOLT-LMM). One to two thirds of the loci identified for allometric body-shape indices were novel. Most prominent was rs72959041 variant in RSPO3 gene, expressed in visceral adipose tissue and regulating adrenal cell renewal. Highly ranked were genes related to morphogenesis and organogenesis, previously additionally linked to cancer development and progression. Genetic associations were fewer in men compared to women. Prominent region-specific associations showed variants in loci VEGFA and HMGA1 for ABSI and KLF14 for HI in women, and C5orf67 and HOXC4/5 for ABSI and RSPO3, VEGFA and SLC30A10 for HI in men. Although more variants were associated with waist and hip circumference adjusted for BMI compared to ABSI and HI, associations with height had previously been reported for many of the additional variants, illustrating the importance of adjusting correctly for height.

Journal article

Pazoki R, Elliott J, Evangelou E, Gill D, Pinto R, Zuber V, Said S, Dehghan A, Tzoulaki I, Jarvelin MR, Thursz M, Elliott Pet al., 2021, Genetic analysis in European ancestry individuals identifies 517 loci associated with liver enzymes, Nature Communications, Vol: 12, ISSN: 2041-1723

Serum concentration of hepatic enzymes are linked to liver dysfunction, metabolic and cardiovascular diseases. We perform genetic analysis on serum levels of alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) using data on 437,438 UK Biobank participants. Replication in 315,572 individuals from European descent from the Million Veteran Program, Rotterdam Study and Lifeline study confirms 517 liver enzyme SNPs. Genetic risk score analysis using the identified SNPs is strongly associated with serum activity of liver enzymes in two independent European descent studies (The Airwave Health Monitoring study and the Northern Finland Birth Cohort 1966). Gene-set enrichment analysis using the identified SNPs highlights involvement in liver development and function, lipid metabolism, insulin resistance, and vascular formation. Mendelian randomization analysis shows association of liver enzyme variants with coronary heart disease and ischemic stroke. Genetic risk score for elevated serum activity of liver enzymes is associated with higher fat percentage of body, trunk, and liver and body mass index. Our study highlights the role of molecular pathways regulated by the liver in metabolic disorders and cardiovascular disease.

Journal article

Eales JM, Jiang X, Xu X, Saluja S, Akbarov A, Cano-Gamez E, McNulty MT, Finan C, Guo H, Wystrychowski W, Szulinska M, Thomas HB, Pramanik S, Chopade S, Prestes PR, Wise I, Evangelou E, Salehi M, Shakanti Y, Ekholm M, Denniff M, Nazgiewicz A, Eichinger F, Godfrey B, Antczak A, Glyda M, Krol R, Eyre S, Brown J, Berzuini C, Bowes J, Caulfield M, Zukowska-Szczechowska E, Zywiec J, Bogdanski P, Kretzler M, Woolf AS, Talavera D, Keavney B, Maffia P, Guzik TJ, O'Keefe RT, Trynka G, Samani NJ, Hingorani A, Sampson MG, Morris AP, Charchar FJ, Tomaszewski Met al., 2021, Uncovering genetic mechanisms of hypertension through multi-omic analysis of the kidney, NATURE GENETICS, Vol: 53, Pages: 630-+, ISSN: 1061-4036

Journal article

Antonatos C, Stavrou EF, Evangelou E, Vasilopoulos Yet al., 2021, Exploring pharmacogenetic variants for predicting response to anti-TNF therapy in autoimmune diseases: a meta-analysis, PHARMACOGENOMICS, Vol: 22, ISSN: 1462-2416

Journal article

Dessinioti C, Geller AC, Stergiopoulou A, Dimou N, Lo S, Keim U, Gershenwald JE, Haydu LE, Dummer R, Mangana J, Hauschild A, Egberts F, Vieira R, Brinca A, Zalaudek I, Deinlein T, Evangelou E, Thompson JF, Scolyer RA, Peris K, Garbe C, Stratigos AJet al., 2021, A multicentre study of naevus-associated melanoma vs. de novo melanoma, tumour thickness and body site differences, BRITISH JOURNAL OF DERMATOLOGY, Vol: 185, Pages: 101-109, ISSN: 0007-0963

Journal article

Surendran P, Feofanova EV, Lahrouchi N, Ntalla I, Karthikeyan S, Cook J, Chen L, Mifsud B, Yao C, Kraja AT, Cartwright JH, Hellwege JN, Giri A, Tragante V, Thorleifsson G, Liu DJ, Prins BP, Stewart ID, Cabrera CP, Eales JM, Akbarov A, Auer PL, Bielak LF, Bis JC, Braithwaite VS, Brody JA, Daw EW, Warren HR, Drenos F, Nielsen SF, Faul JD, Fauman EB, Fava C, Ferreira T, Foley CN, Franceschini N, Gao H, Giannakopoulou O, Giulianini F, Gudbjartsson DF, Guo X, Harris SE, Havulinna AS, Helgadottir A, Huffman JE, Hwang S-J, Kanoni S, Kontto J, Larson MG, Li-Gao R, Lindstrom J, Lotta LA, Lu Y, Luan J, Mahajan A, Malerba G, Masca NGD, Mei H, Menni C, Mook-Kanamori DO, Mosen-Ansorena D, Muller-Nurasyid M, Pare G, Paul DS, Perola M, Poveda A, Rauramaa R, Richard M, Richardson TG, Sepulveda N, Sim X, Smith AV, Smith JA, Staley JR, Stanakova A, Sulem P, Theriault S, Thorsteinsdottir U, Trompet S, Varga TV, Velez Edwards DR, Veronesi G, Weiss S, Willems SM, Yao J, Young R, Yu B, Zhang W, Zhao J-H, Zhao W, Zhao W, Evangelou E, Aeschbacher S, Asllanaj E, Blankenberg S, Bonnycastle LL, Bork-Jensen J, Brandslund I, Braund PS, Burgess S, Cho K, Christensen C, Connell J, de Mutsert R, Dominiczak AF, Dorr M, Eiriksdottir G, Farmaki A-E, Gaziano JM, Grarup N, Grove ML, Hallmans G, Hansen T, Have CT, Heiss G, Jorgensen ME, Jousilahti P, Kajantie E, Kamat M, Karajamaki A, Karpe F, Koistinen HA, Kovesdy CP, Kuulasmaa K, Laatikainen I, Lannfelt L, Lee I-T, Lee W-J, Linneberg A, Martin LW, Moitry M, Nadkarni G, Neville MJ, Palmer CNA, Papanicolaou GJ, Pedersen O, Peters J, Poulter N, Rasheed A, Rasmussen KL, Rayner NW, Magi R, Renstrom F, Rettig R, Rossouw J, Schreiner PJ, Sever PS, Sigurdsson EL, Skaaby T, Sun YV, Sundstrom J, Thorgeirsson G, Esko T, Trabetti E, Tsao PS, Tuomi T, Turner ST, Tzoulaki I, Vaartjes I, Vergnaud A-C, Willer CJ, Wilson PWF, Witte DR, Yonova-Doing E, Zhang H, Aliya N, Almgren P, Amouyel P, Asselbergs FW, Barnes MR, Blakemore AI, Boehnke M, Bots ML, Bottinger EP, Buriet al., 2021, Publisher Correction: Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals, Nature Genetics, Vol: 53, Pages: 1-2, ISSN: 1061-4036

Journal article

Georgiopoulos G, Ntritsos G, Stamatelopoulos K, Tsioufis C, Aimo A, Masi S, Evangelou Eet al., 2021, The relationship between blood pressure and risk of atrial fibrillation: a Mendelian randomization study., Eur J Prev Cardiol

AIMS: Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF. METHODS AND RESULTS: Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N = 299 024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including >1 000 000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1 mmHg increase, 95% confidence interval (CI): 1.012-1.024, P < 0.001], DBP (OR: 1.026, 95% CI: 1.016-1.035, P < 0.001), and PP (OR: 1.014, 95% CI: 1.001-1.028, P = 0.033). These findings were robust in sensitivity analyses, including the MR-Egger method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). The causal relationship of BP and AF did not change when single-nucleotide polymorphisms associated with possible confounders (i.e. coronary artery disease and obesity) of the causal relationship were excluded. CONCLUSIONS: The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population.

Journal article

Gill D, Cameron AC, Burgess S, Li X, Doherty DJ, Karhunen V, Abdul-Rahim AH, Taylor-Rowan M, Zuber V, Tsao PS, Klarin D, VA Million Veteran Program, Evangelou E, Elliott P, Damrauer SM, Quinn TJ, Dehghan A, Theodoratou E, Dawson J, Tzoulaki Iet al., 2021, Urate, blood pressure and cardiovascular disease: evidence from Mendelian randomization and meta-analysis of clinical trials, Hypertension, Vol: 77, Pages: 383-392, ISSN: 0194-911X

Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10–1.30]; P=4×10−5), peripheral artery disease (1.12 [95% CI, 1.03–1.21]; P=9×10−3), and stroke (1.11 [95% CI, 1.05–1.18]; P=2×10−4). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, −2.55 mm Hg [95% CI, −4.06 to −1.05]; P=1×10−3) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22–0.73]; P=3×10−3) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44–1.03]; P=0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.

Journal article

Evangelou E, Suzuki H, Bai W, Pazoki R, Gao H, Matthews PM, Elliott Pet al., 2021, Alcohol consumption is associated with structural changes in various organ systems: A population-based study in UK Biobank

<jats:title>Abstract</jats:title><jats:p>Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample. We assessed global effects of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta and liver of UK-Biobank participants who reported drinking alcohol. We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (–1.7×10<jats:sup>−3</jats:sup>±0.76×10<jats:sup>−3</jats:sup> per doubling of alcohol consumption, <jats:italic>P</jats:italic>=3.0×10<jats:sup>−14</jats:sup>). Alcohol consumption also was associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption. Our results imply that there is not a “safe threshold” below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.</jats:p>

Journal article

Georgiou AN, Ntritsos G, Papadimitriou N, Dimou N, Evangelou Eet al., 2021, Cigarette Smoking, Coffee Consumption, Alcohol Intake, and Risk of Crohn's Disease and Ulcerative Colitis: A Mendelian Randomization Study, INFLAMMATORY BOWEL DISEASES, Vol: 27, Pages: 162-168, ISSN: 1078-0998

Journal article

Lagou V, Jiang L, Ulrich A, Zudina L, González KSG, Balkhiyarova Z, Faggian A, Chen S, Todorov P, Sharapov S, David A, Marullo L, Mägi R, Rujan R-M, Ahlqvist E, Thorleifsson G, Gao H, Evangelou E, Benyamin B, Scott R, Isaacs A, Zhao JH, Willems SM, Johnson T, Gieger C, Grallert H, Meisinger C, Müller-Nurasyid M, Strawbridge RJ, Goel A, Rybin D, Albrecht E, Jackson AU, Stringham HM, Corrêa IR, Eric F-E, Steinthorsdottir V, Uitterlinden AG, Munroe PB, Brown MJ, Julian S, Holmen O, Thorand B, Hveem K, Wilsgaard T, Mohlke KL, Kratzer W, Mark H, Koenig W, Boehm BO, Tan TM, Tomas A, Salem V, Barroso I, Tuomilehto J, Boehnke M, Florez JC, Hamsten A, Watkins H, Njølstad I, Wichmann H-E, Caulfield MJ, Khaw K-T, van Duijn C, Hofman A, Wareham NJ, Langenberg C, Whitfield JB, Martin NG, Montgomery G, Scapoli C, Tzoulaki I, Elliott P, Thorsteinsdottir U, Stefansson K, Brittain EL, McCarthy MI, Froguel P, Sexton PM, Wootten D, Groop L, Dupuis J, Meigs JB, Deganutti G, Demirkan A, Pers TH, Reynolds CA, Aulchenko YS, Kaakinen MA, Jones B, Prokopenko I, Glucose OBOTM-AO, MAGIC I-RTCet al., 2021, Random glucose GWAS in 493,036 individuals provides insights into diabetes pathophysiology, complications and treatment stratification, medRxiv

Homeostatic control of blood glucose requires different physiological responses in the fasting and post-prandial states. We reasoned that glucose measurements under non-standardised conditions (random glucose; RG) may capture diverse glucoregulatory processes more effectively than previous genome-wide association studies (GWAS) of fasting glycaemia or after standardised glucose loads. Through GWAS meta-analysis of RG in 493,036 individuals without diabetes of diverse ethnicities we identified 128 associated loci represented by 162 distinct signals, including 14 with sex-dimorphic effects, 9 discovered through trans-ethnic analysis, and 70 novel signals for glycaemic traits. Novel RG loci were particularly enriched in expression in the ileum and colon, indicating a prominent role for the gastrointestinal tract in the control of blood glucose. Functional studies and molecular dynamics simulations of coding variants of GLP1R, a well-established type 2 diabetes treatment target, provided a genetic framework for optimal selection of GLP-1R agonist therapy. We also provided new evidence from Mendelian randomisation that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Thus, our approach based on RG GWAS provided wide-ranging insights into the biology of glucose regulation, diabetes complications and the potential for treatment stratification.Competing Interest StatementAlejandra Tomas has received grant funding from Sun Pharmaceuticals. Ivan R Corrêa, Jr is an employee of New England Biolabs, Inc., a manufacturer and vendor of reagents for life science research. Mark J Caulfield is Chief Scientist for Genomics England, a UK Government company. The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Mark McCarthy has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo No

Journal article

Sargurupremraj M, Suzuki H, Jian X, Sarnowski C, Evans TE, Bis JC, Eiriksdottir G, Sakaue S, Terzikhan N, Habes M, Zhao W, Armstrong NJ, Hofer E, Yanek LR, Hagenaars SP, Kumar RB, van den Akker EB, McWhirter RE, Trompet S, Mishra A, Saba Y, Satizabal CL, Beaudet G, Petit L, Tsuchida A, Zago L, Schilling S, Sigurdsson S, Gottesman RF, Lewis CE, Aggarwal NT, Lopez OL, Smith JA, Valdés Hernández MC, van der Grond J, Wright MJ, Knol MJ, Dörr M, Thomson RJ, Bordes C, Le Grand Q, Duperron M-G, Smith AV, Knopman DS, Schreiner PJ, Evans DA, Rotter JI, Beiser AS, Maniega SM, Beekman M, Trollor J, Stott DJ, Vernooij MW, Wittfeld K, Niessen WJ, Soumaré A, Boerwinkle E, Sidney S, Turner ST, Davies G, Thalamuthu A, Völker U, van Buchem MA, Bryan RN, Dupuis J, Bastin ME, Ames D, Teumer A, Amouyel P, Kwok JB, Bülow R, Deary IJ, Schofield PR, Brodaty H, Jiang J, Tabara Y, Setoh K, Miyamoto S, Yoshida K, Nagata M, Kamatani Y, Matsuda F, Psaty BM, Bennett DA, De Jager PL, Mosley TH, Sachdev PS, Schmidt R, Warren HR, Evangelou E, Trégouët D-A, International Network against Thrombosis INVENT Consortium, International Headache Genomics Consortium IHGC, Ikram MA, Wen W, DeCarli C, Srikanth VK, Jukema JW, Slagboom EP, Kardia SLR, Okada Y, Mazoyer B, Wardlaw JM, Nyquist PA, Mather KA, Grabe HJ, Schmidt H, Van Duijn CM, Gudnason V, Longstreth WT, Launer LJ, Lathrop M, Seshadri S, Tzourio C, Adams HH, Matthews PM, Fornage M, Debette Set al., 2020, Cerebral small vessel disease genomics and its implications across the lifespan, Nature Communications, Vol: 11, ISSN: 2041-1723

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

Journal article

Cabrera CP, Pazoki R, Giri A, Hellwege JN, Evangelou E, Ramirez J, Wain LV, Tzoulaki I, Edwards TL, Elliott P, Munroe PB, Barnes MR, Caulfield MJ, Warren HRet al., 2020, Multi-trait genome-wide association analysis of blood pressure identifies 45 additional loci, Publisher: SPRINGERNATURE, Pages: 105-105, ISSN: 1018-4813

Conference paper

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