Imperial College London

Dr Kenan Direk

Faculty of MedicineSchool of Public Health

Principal Data Manager
 
 
 
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Contact

 

kenan.direk08

 
 
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Location

 

St Marys Multiple BuildingsSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
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34 results found

Webber M, Joy G, Bennett J, Chan F, Falconer D, Shiwani H, Davies RH, Krausz G, Tanackovic S, Guger C, Gonzalez P, Martin E, Wong A, Rapala A, Direk K, Kellman P, Pierce I, Rudy Y, Vijayakumar R, Chaturvedi N, Hughes AD, Moon JC, Lambiase PD, Tao X, Koncar V, Orini M, Captur Get al., 2023, Technical development and feasibility of a reusable vest to integrate cardiovascular magnetic resonance with electrocardiographic imaging., J Cardiovasc Magn Reson, Vol: 25

BACKGROUND: Electrocardiographic imaging (ECGI) generates electrophysiological (EP) biomarkers while cardiovascular magnetic resonance (CMR) imaging provides data about myocardial structure, function and tissue substrate. Combining this information in one examination is desirable but requires an affordable, reusable, and high-throughput solution. We therefore developed the CMR-ECGI vest and carried out this technical development study to assess its feasibility and repeatability in vivo. METHODS: CMR was prospectively performed at 3T on participants after collecting surface potentials using the locally designed and fabricated 256-lead ECGI vest. Epicardial maps were reconstructed to generate local EP parameters such as activation time (AT), repolarization time (RT) and activation recovery intervals (ARI). 20 intra- and inter-observer and 8 scan re-scan repeatability tests. RESULTS: 77 participants were recruited: 27 young healthy volunteers (HV, 38.9 ± 8.5 years, 35% male) and 50 older persons (77.0 ± 0.1 years, 52% male). CMR-ECGI was achieved in all participants using the same reusable, washable vest without complications. Intra- and inter-observer variability was low (correlation coefficients [rs] across unipolar electrograms = 0.99 and 0.98 respectively) and scan re-scan repeatability was high (rs between 0.81 and 0.93). Compared to young HV, older persons had significantly longer RT (296.8 vs 289.3 ms, p = 0.002), ARI (249.8 vs 235.1 ms, p = 0.002) and local gradients of AT, RT and ARI (0.40 vs 0.34 ms/mm, p = 0,01; 0.92 vs 0.77 ms/mm, p = 0.03; and 1.12 vs 0.92 ms/mm, p = 0.01 respectively). CONCLUSION: Our high-throughput CMR-ECGI solution is feasible and shows good reproducibility in younger and older participants. This new technology is now scalable for high throughput research to provide novel insig

Journal article

Topriceanu C-C, Dev E, Ahmad M, Hughes R, Shiwani H, Webber M, Direk K, Wong A, Ugander M, Moon JC, Hughes AD, Maddock J, Schlegel TT, Captur Get al., 2023, Accelerated DNA methylation age plays a role in the impact of cardiovascular risk factors on the human heart., Clin Epigenetics, Vol: 15

BACKGROUND: DNA methylation (DNAm) age acceleration (AgeAccel) and cardiac age by 12-lead advanced electrocardiography (A-ECG) are promising biomarkers of biological and cardiac aging, respectively. We aimed to explore the relationships between DNAm age and A-ECG heart age and to understand the extent to which DNAm AgeAccel relates to cardiovascular (CV) risk factors in a British birth cohort from 1946. RESULTS: We studied four DNAm ages (AgeHannum, AgeHorvath, PhenoAge, and GrimAge) and their corresponding AgeAccel. Outcomes were the results from two publicly available ECG-based cardiac age scores: the Bayesian A-ECG-based heart age score of Lindow et al. 2022 and the deep neural network (DNN) ECG-based heart age score of Ribeiro et al. 2020. DNAm AgeAccel was also studied relative to results from two logistic regression-based A-ECG disease scores, one for left ventricular (LV) systolic dysfunction (LVSD), and one for LV electrical remodeling (LVER). Generalized linear models were used to explore the extent to which any associations between biological cardiometabolic risk factors (body mass index, hypertension, diabetes, high cholesterol, previous cardiovascular disease [CVD], and any CV risk factor) and the ECG-based outcomes are mediated by DNAm AgeAccel. We derived the total effects, average causal mediation effects (ACMEs), average direct effects (ADEs), and the proportion mediated [PM] with their 95% confidence intervals [CIs]. 498 participants (all 60-64 years) were included, with the youngest ECG heart age being 27 and the oldest 90. When exploring the associations between cardiometabolic risk factors and Bayesian A-ECG cardiac age, AgeAccelPheno appears to be a partial mediator, as ACME was 0.23 years [0.01, 0.52] p = 0.028 (i.e., PM≈18%) for diabetes, 0.34 [0.03, 0.74] p = 0.024 (i.e., PM≈15%) for high cholesterol, and 0.34 [0.03, 0.74] p = 0.024 (P

Journal article

Banerjee A, Pasea L, Chung S-C, Direk K, Asselbergs F, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway Het al., 2022, A population-based study of 92 clinicallyrecognized risk factors for heart failure: co-occurrence, prognosis and preventive potential (vol 24, pg 466, 2022), EUROPEAN JOURNAL OF HEART FAILURE, Vol: 24, Pages: 1739-1739, ISSN: 1388-9842

Journal article

Huebner GM, Oreszczyn T, Direk K, Hamilton Iet al., 2022, The relationship between the built environment and subjective wellbeing - Analysis of cross-sectional data from the English Housing Survey, JOURNAL OF ENVIRONMENTAL PSYCHOLOGY, Vol: 80, ISSN: 0272-4944

Journal article

Banerjee A, Pasea L, Chung S-C, Direk K, Asselbergs F, Grobbee DE, Kotecha D, Anker SD, Dyszynski T, Tyl B, Denaxas S, Lumbers RT, Hemingway Het al., 2022, A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 24, Pages: 466-480, ISSN: 1388-9842

Journal article

Kuan V, Fraser HC, Hingorani M, Denaxas S, Gonzalez-Izquierdo A, Direk K, Nitsch D, Mathur R, Parisinos CA, Lumbers RT, Sofat R, Wong ICK, Casas JP, Thornton JM, Hemingway H, Partridge L, Hingorani ADet al., 2021, Data-driven identification of ageing-related diseases from electronic health records, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322

Journal article

Huebner GM, Watson NE, Direk K, McKenna E, Webborn E, Hollick F, Elam S, Oreszczyn Tet al., 2021, Survey study on energy use in UK homes during Covid-19, Buildings and Cities, Vol: 2, Pages: 952-969

To contain the spread of Covid-19, governments across the world imposed partial or complete lockdowns. National energy demand decreased in periods of lockdowns; however, as people spent more time at home, residential energy use likely increased. This paper reports the results of a UK survey study (N = 1016 participants) about their energy-use practices during the first lockdown in March 2020. The results indicated that self-reported heating behaviours did not substantially change during lockdown. Regarding appliance use, in particular the duration of usage for televisions and computing equipment has increased and has spread more over the day. Being less able to manage financially was correlated with a greater usage of the smart meter in-home display and a greater attempt to save energy was positively correlated with greater usage of the in-home display, though correlations were small. In summary, the results indicate that home energy-use behaviours, in particular around heating, did not change as much as might have been expected, which might at least partly be explained by the comparatively warm weather during the first lockdown. Corroborating the survey findings with actual energy data is the next essential step to understand findings in more detail. POLICY RELEVANCE Governments are developing policies to support the transition to net zero. Covid-19 has accelerated the transition in behaviours such as home working which may result in a ‘new normal’ energy behaviour and will need to be taken account when planning for net zero. Insights into the changes in behaviour during lockdown indicate it would be oversimplified to assume that electricity and gas use have increased in all homes because of a stay-at-home order. Self-reported heating did not change, whereas electrical appliance usage increased. The sample composition of the household is important for understanding the energy implications. In this study, about half the households did not spend more time

Journal article

Nanjo A, Evans H, Direk K, Hayward AC, Story A, Banerjee Aet al., 2020, Prevalence, incidence, and outcomes across cardiovascular diseases in homeless individuals using national linked electronic health records, EUROPEAN HEART JOURNAL, Vol: 41, Pages: 4011-4020, ISSN: 0195-668X

Journal article

Banerjee A, Nanjo A, Evans H, Direk K, Hayward A, Story Aet al., 2020, Prevalence, incidence, and outcomes across cardiovascular diseases in homeless individuals- a case-control study using national linked electronic health records, European-Society-of-Cardiology (ESC) Congress, Publisher: OXFORD UNIV PRESS, Pages: 3517-3517, ISSN: 0195-668X

Conference paper

Banerjee A, Pasea L, Chung SC, Direk K, Asselbergs FW, Denaxas S, Hemingway Het al., 2020, 92 aetiologic factors for heart failure: prevalence, co-occurrence, prognosis and potential for prevention in 170,885 incident HF cases, European-Society-of-Cardiology (ESC) Congress, Publisher: OXFORD UNIV PRESS, Pages: 1134-1134, ISSN: 0195-668X

Conference paper

Mahmoodi BK, Tragante V, Kleber ME, Holmes MV, Schmidt AF, McCubrey RO, Howe LJ, Direk K, Allayee H, Baranova EV, Braund PS, Delgado GE, Eriksson N, Gijsberts CM, Gong Y, Hartiala J, Heydarpour M, Pasterkamp G, Kotti S, Kuukasjarvi P, Lenzini PA, Levin D, Lyytikainen L-P, Muehlschlegel JD, Nelson CP, Nikus K, Pilbrow AP, Wilson Tang WH, van der Laan SW, van Setten J, Vilmundarson RO, Deanfield J, Deloukas P, Dudbridge F, James S, Mordi IR, Teren A, Bergmeijer TO, Body SC, Bots M, Burkhardt R, Cooper-DeHoff RM, Cresci S, Danchin N, Doughty RN, Grobbee DE, Hagstrom E, Hazen SL, Held C, Hoefer IE, Hovingh GK, Johnson JA, Kaczor MP, Kahonen M, Klungel OH, Laurikka JO, Lehtimaki T, van der Zee AH, McPherson R, Palmer CN, Kraaijeveld AO, Pepine CJ, Sanak M, Sattar N, Scholz M, Simon T, Spertus JA, Stewart AFR, Szczeklik W, Thiery J, Visseren FLJ, Waltenberger J, Richards AM, Lang CC, Cameron VA, akerblom A, Pare G, Maerz W, Samani NJ, Hingorani AD, ten Berg JM, Wallentin L, Asselbergs FW, Patel RSet al., 2020, Association of Factor V Leiden With Subsequent Atherothrombotic Events A GENIUS-CHD Study of Individual Participant Data, CIRCULATION, Vol: 142, Pages: 546-555, ISSN: 0009-7322

Journal article

Denaxas S, Gonzalez-Izquierdo A, Direk K, Fitzpatrick NK, Fatemifar G, Banerjee A, Dobson RJB, Howe LJ, Kuan V, Lumbers RT, Pasea L, Patel RS, Shah AD, Hingorani AD, Sudlow C, Hemingway Het al., 2019, UK phenomics platform for developing and validating electronic health record phenotypes: CALIBER, JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION, Vol: 26, Pages: 1545-1559, ISSN: 1067-5027

Journal article

Mackintosh M, Aldridge RW, Rossor M, Gonzalez-Izquierdo A, Whitaker KJ, Ford E, Direk K, Denaxas Set al., 2019, Dementia recognition, diagnosis, and treatment in the UK, 1997-2017: a change-point analysis, National Conference on Public Health Science Dedicated to New Research in UK Public Health, Publisher: ELSEVIER SCIENCE INC, Pages: 70-70, ISSN: 0140-6736

Conference paper

Uijl A, Koudstaal S, Direk K, Denaxas S, Groenwold RHH, Banerjee A, Hoes AW, Hemingway H, Asselbergs FWet al., 2019, Risk factors for incident heart failure in age- and sex-specific strata: a population-based cohort using linked electronic health records, EUROPEAN JOURNAL OF HEART FAILURE, Vol: 21, Pages: 1197-1206, ISSN: 1388-9842

Journal article

Leon LJ, McCarthy FP, Direk K, Gonzalez-Izquierdo A, Prieto-Merino D, Casas JP, Chappell Let al., 2019, Preeclampsia and Cardiovascular Disease in a Large UK Pregnancy Cohort of Linked Electronic Health Records A CALIBER Study, CIRCULATION, Vol: 140, Pages: 1050-1060, ISSN: 0009-7322

Journal article

Kuan V, Denaxas S, Gonzalez-Izquierdo A, Direk K, Bhatti O, Husain S, Sutaria S, Hingorani M, Nitsch D, Parisinos CA, Lumbers RT, Mathur R, Sofat R, Casas JP, Wong ICK, Hemingway H, Hingorani ADet al., 2019, A chronological map of 308 physical and mental health conditions from 4 million individuals in the English National Health Service, LANCET DIGITAL HEALTH, Vol: 1, Pages: E63-E77

Journal article

Patel RS, Schmidt AF, Tragante V, McCubrey RO, Holmes M, Howe LJ, Direk K, Akerblom A, Leander K, Virani SS, Kaminski KA, Muehlschlegel JD, Dube M-P, Allayee H, Almgren P, Alver M, Baranova E, Behlouli H, Boeckx B, Braund PS, Breitling LP, Delgado G, Duarte NE, Dufresne L, Eriksson N, Foco L, Gijsberts CM, Gong Y, Hartiala J, Heydarpour M, Hubacek JA, Kleber M, Kofink D, Kuukasjarvi P, Lee V-V, Leiherer A, Lenzini PA, Levin D, Lyytikainen L-P, Martinelli N, Mons U, Nelson CP, Nikus K, Pilbrow AP, Ploski R, Sun Y, Tanck MWT, Tang WHW, Trompet S, van der Laan SW, van Setten J, Vilmundarson RO, Anselmi CV, Vlachopoulou E, Boerwinkle E, Briguori C, Carlquist JF, Carruthers KF, Casu G, Deanfield J, Deloukas P, Dudbridge F, Fitzpatrick N, Gigante B, James S, Lokki M-L, Lotufo PA, Marziliano N, Mordi IR, Muhlestein JB, Cheh CN, Pitha J, Saely CH, Samman-Tahhan A, Sandesara PB, Teren A, Timmis A, Van de Werf F, Wauters E, Wilde AAM, Ford I, Stott DJ, Algra A, Andreassi MG, Ardissino D, Arsenault BJ, Ballantyne CM, Bergmeijer TO, Bezzina CR, Body SC, Bogaty P, de Borst GJ, Brenner H, Burkhardt R, Carpeggiani C, Condorelli G, Cooper-DeHoff RM, Cresci S, de Faire U, Doughty RN, Drexel H, Engert JC, Fox KAA, Girelli D, Hagstrom E, Hazen SL, Held C, Hemingway H, Hoefer IE, Hovingh GK, Johnson JA, De Jong PA, Jukema JW, Kaczor MP, Kahonen M, Kettner J, Kiliszek M, Klungel OH, Lagerqvist B, Lambrechts D, Laurikka JO, Lehtimaki T, Lindholm D, Mahmoodi BK, Maitland-van der Zee AH, McPherson R, Melander O, Metspalu A, Pepinski W, Olivieri O, Opolski G, Palmer CN, Pasterkamp G, Pepine CJ, Pereira AC, Note L, Quyyumi AA, Richards AM, Sanak M, Scholz M, Siegbahn A, Sinisalo J, Smith JG, Spertus JA, Stewart AFR, Szczeklik W, Szpakowicz A, ten Berg JM, Thanassoulis G, Thieiy J, van der Graaf Y, Visseren FLJ, Waltenberger J, Van der Harst P, Tardif J-C, Sattar N, Lang CC, Pare G, Brophy JM, Anderson JL, Maerz W, Wallentin L, Cameron VA, Horne BD, Samani NJ, Hingorani AD, Asselbergs FWet al., 2019, Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events A GENIUS-CHD Study of Individual Participant Data, CIRCULATION-GENOMIC AND PRECISION MEDICINE, Vol: 12, ISSN: 2574-8300

Journal article

Patel R, Tragante V, Schmidt AF, McCubrey RO, Holmes MV, Howe LJ, Direk K, Åkerblom A, Leander K, Virani SS, Kaminski KA, Muehlschlegel JD, Allayee H, Almgren P, Alver M, Baranova EV, Behlouli H, Boeckx B, Braund PS, Breitling LP, Delgado G, Duarte NE, Dubé M-P, Dufresne L, Eriksson N, Foco L, Scholz M, Gijsberts CM, Glinge C, Gong Y, Hartiala J, Heydarpour M, Hubacek JA, Kleber M, Kofink D, Kotti S, Kuukasjärvi P, Lee V-V, Leiherer A, Lenzini PA, Levin D, Lyytikäinen L-P, Martinelli N, Mons U, Nelson CP, Nikus K, Pilbrow AP, Ploski R, Sun YV, Tanck MWT, Tang WHW, Trompet S, van der Laan SW, Van Setten J, Vilmundarson RO, Viviani Anselmi C, Vlachopoulou E, Al Ali L, Boerwinkle E, Briguori C, Carlquist JF, Carruthers KF, Casu G, Deanfield J, Deloukas P, Dudbridge F, Engström T, Fitzpatrick N, Fox K, Gigante B, James S, Lokki M-L, Lotufo PA, Marziliano N, Mordi IR, Muhlestein JB, Newton-Cheh C, Pitha J, Saely CH, Samman-Tahhan A, Sandesara PB, Teren A, Timmis A, Van de Werf F, Wauters E, Wilde AAM, Ford I, Stott DJ, Algra A, Andreassi MG, Ardissino D, Arsenault BJ, Ballantyne CM, Bergmeijer TO, Bezzina CR, Body SC, Boersma EH, Bogaty P, Bots M, Brenner H, Brugts JJ, Burkhardt R, Carpeggiani C, Condorelli G, Cooper-DeHoff RM, Cresci S, Danchin N, de Faire U, Doughty RN, Drexel H, Engert JC, Fox KAA, Girelli D, Grobbee DE, Hagström E, Hazen SL, Held C, Hemingway H, Hoefer IE, Hovingh GK, Jabbari R, Johnson JA, Jukema JW, Kaczor MP, Kähönen M, Kettner J, Kiliszek M, Klungel OH, Lagerqvist B, Lambrechts D, Laurikka JO, Lehtimäki T, Lindholm D, Mahmoodi BK, Maitland-van der Zee AH, McPherson R, Melander O, Metspalu A, Niemcunowicz-Janica A, Olivieri O, Opolski G, Palmer CN, Pasterkamp G, Pepine CJ, Pereira AC, Pilote L, Quyyumi AA, Richards AM, Sanak M, Siegbahn A, Simon T, Sinisalo J, Smith JG, Spertus JA, Stender S, Stewart AFR, Szczeklik W, Szpakowicz A, Tardif J-C, Ten Berg JM, Tfelt-Hansen J, Thanassoulis G, Thiery J, Torp-Pedersen C, van der Graaf Y, Visseren FLJ, Waet al., 2019, Subsequent Event Risk in Individuals with Established Coronary Heart Disease: Design and Rationale of the GENIUS-CHD Consortium., Circ Genom Precis Med

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.

Journal article

Williamson E, Denaxas S, Morris S, Clarke CS, Thomas M, Evans H, Direk K, Gonzalez-Izquierdo A, Little P, Lund V, Blackshaw H, Schilder A, Philpott C, Hopkins C, Carpenter Jet al., 2019, Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records, RHINOLOGY, Vol: 57, Pages: 252-260, ISSN: 0300-0729

Journal article

Mackintosh M, Gonzalez-Izquierdo A, Rossor M, Whitaker K, Direk K, Denaxas Set al., 2019, Network Structures and Dynamics Of Early Dementia Events Recorded in Primary Care Electronic Health Records, 9th International Conference on Digital Public Health (DPH), Publisher: ASSOC COMPUTING MACHINERY, Pages: 127-127

Conference paper

Denaxas S, Gonzalez-Izquierdo A, Fitzpatrick N, Direk K, Hemingway Het al., 2019, Phenotyping UK Electronic Health Records from 15 Million Individuals for Precision Medicine: he CALIBER Resource, HEALTH INFORMATICS VISION: FROM DATA VIA INFORMATION TO KNOWLEDGE, Vol: 262, Pages: 220-223, ISSN: 0926-9630

Journal article

Härmälä S, O'Brien A, Parisinos CA, Direk K, Shallcross L, Hayward Aet al., 2019, Development and validation of a prediction model to estimate the risk of liver cirrhosis in primary care patients with abnormal liver blood test results: protocol for an electronic health record study in Clinical Practice Research Datalink., Diagn Progn Res, Vol: 3

BACKGROUND: Driven by alcohol consumption and obesity, the prevalence of non-viral liver disease in the UK is increasing. Due to its silent and slow nature, the progression of liver disease is currently unpredictable and challenging to monitor. The latest National Institute for Health Care Excellence cirrhosis guidelines call for a validated risk tool that would allow general practitioners to identify patients that are at high risk of developing cirrhosis. METHODS: Using linked electronic health records from the Clinical Practice Research Datalink (a database of > 10 million patients in England), we aim to develop and validate a prediction model to estimate 2-, 5- and 10-year risk of cirrhosis. The model will provide individualised cirrhosis risk predictions for adult primary care patients, free from underlying liver disease or viral hepatitis infection, whose liver blood test results come back abnormal. We will externally validate the model in patients from 30 further Clinical Practice Research Datalink general practices in England. DISCUSSION: The prediction model will provide estimates of cirrhosis risk in primary care patients with abnormal liver blood test results to guide referral to secondary care, to identify patients who are in serious need of preventative health interventions and to help reassure patients at low risk of cirrhosis in the long term.

Journal article

Pikoula M, Quint JK, Direk K, Nissen F, Gonzalez-Izquierdo A, Hemingway H, Smeeth L, Denaxas Set al., 2018, Discovery of Novel COPD Subtypes Via Cluster Analysis of Clinical Features Extracted from Electronic Health Records, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Hu YJ, Schmidt AF, Dudbridge F, Holmes MV, Brophy JM, Tragante V, Li Z, Liao P, Quyyumi AA, McCubrey RO, Horne BD, Hingorani AD, Asselbergs FW, Patel RS, Long Q, Åkerblom A, Algra A, Allayee H, Almgren P, Anderson JL, Andreassi MG, Anselmi CV, Ardissino D, Arsenault BJ, Ballantyne CM, Baranova EV, Behloui H, Bergmeijer TO, Bezzina CR, Bjornsson E, Body SC, Boeckx B, Boersma EH, Boerwinkle E, Bogaty P, Braund PS, Breitling LP, Brenner H, Briguori C, Brugts JJ, Burkhardt R, Cameron VA, Carlquist JF, Carpeggiani C, Carruthers KF, Casu G, Condorelli G, Cresci S, Danchin N, De Faire U, Deanfield J, Delgado G, Deloukas P, Direk K, Doughty RN, Drexel H, Duarte NE, Dubé MP, Dufresne L, Engert JC, Eriksson N, Fitzpatrick N, Foco L, Ford I, Fox KAA, Gigante B, Gijsberts CM, Girelli D, Gong Y, Gudbjartsson DF, Hagström E, Hartiala J, Hazen SL, Held C, Helgadottir A, Hemingway H, Heydarpour M, Hoefer IE, Hovingh K, Hubacek JA, James S, Johnson JA, Jukema JW, Kaczor MP, Kaminski KA, Kettner J, Kiliszek M, Kleber M, Klungel OH, Kofink D, Kohonen M, Kotti S, Kuukasjärvi P, Lagerqvist B, Lambrechts D, Lang CC, Laurikka JO, Leander K, Lee VV, Lehtimäki Tet al., 2017, Impact of Selection Bias on Estimation of Subsequent Event Risk, Circulation: Cardiovascular Genetics, Vol: 10, ISSN: 1942-325X

Background - Studies of recurrent or subsequent disease events may be susceptible to bias caused by selection of subjects who both experience and survive the primary indexing event. Currently, the magnitude of any selection bias, particularly for subsequent time-to-event analysis in genetic association studies, is unknown. Methods and Results - We used empirically inspired simulation studies to explore the impact of selection bias on the marginal hazard ratio for risk of subsequent events among those with established coronary heart disease. The extent of selection bias was determined by the magnitudes of genetic and nongenetic effects on the indexing (first) coronary heart disease event. Unless the genetic hazard ratio was unrealistically large (>1.6 per allele) and assuming the sum of all nongenetic hazard ratios was <10, bias was usually <10% (downward toward the null). Despite the low bias, the probability that a confidence interval included the true effect decreased (undercoverage) with increasing sample size because of increasing precision. Importantly, false-positive rates were not affected by selection bias. Conclusions - In most empirical settings, selection bias is expected to have a limited impact on genetic effect estimates of subsequent event risk. Nevertheless, because of undercoverage increasing with sample size, most confidence intervals will be over precise (not wide enough). When there is no effect modification by history of coronary heart disease, the false-positive rates of association tests will be close to nominal.

Journal article

Denaxas S, Direk K, Gonzalez-Izquierdo A, Pikoula M, Cakiroglu A, Moore J, Hemingway H, Smeeth Let al., 2017, Methods for enhancing the reproducibility of biomedical research findings using electronic health records, BIODATA MINING, Vol: 10, ISSN: 1756-0381

Journal article

Zewinger S, Kleber ME, Tragante V, McCubrey RO, Schmidt AF, Direk K, Laufs U, Werner C, Koenig W, Rothenbacher D, Mons U, Breitling LP, Brenner H, Jennings RT, Petrakis I, Triem S, Klug M, Filips A, Blankenberg S, Waldeyer C, Sinning C, Schnabel RB, Lackner KJ, Vlachopoulou E, Nygard O, Svingen GFT, Pedersen ER, Tell GS, Sinisalo J, Nieminen MS, Laaksonen R, Trompet S, Smit RAJ, Sattar N, Jukema JW, Groesdonk HV, Delgado G, Stojakovic T, Pilbrow AP, Cameron VA, Richards AM, Doughty RN, Gong Y, Cooper-DeHoff R, Johnson J, Scholz M, Beutner F, Thiery J, Smith JG, Vilmundarson RO, McPherson R, Stewart AFR, Cresci S, Lenzini PA, Spertus JA, Olivieri O, Girelli D, Martinelli NI, Leiherer A, Saely CH, Drexel H, Muendlein A, Braund PS, Nelson CP, Samani NJ, Kofink D, Hoefer IE, Pasterkamp G, Quyyumi AA, Ko Y-A, Hartiala JA, Allayee H, Tang WHW, Hazen SL, Eriksson N, Held C, Hagstrom E, Wallentin L, Akerblom A, Siegbahn A, Karp I, Labos C, Pilote L, Engert JC, Brophy JM, Thanassoulis G, Bogaty P, Szczeklik W, Kaczor M, Sanak M, Virani SS, Ballantyne CM, Lee V-V, Boerwinkle E, Holmes MV, Horne BD, Hingorani A, Asselbergs FW, Patel RS, Kraemer BK, Scharnagl H, Fliser D, Maerz W, Speer Tet al., 2017, Relations between lipoprotein(a) concentrations, <i>LPA</i> genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study, LANCET DIABETES & ENDOCRINOLOGY, Vol: 5, Pages: 534-543, ISSN: 2213-8587

Journal article

Denaxas S, Gonzalez-Izquierdo A, Pikoula M, Direk K, Fitzpatrick N, Hemingway H, Smeeth Let al., 2017, Methods for enhancing the reproducibility of observational research using electronic health records: preliminary findings from the CALIBER resource, 30th IEEE International Symposium on Computer-Based Medical Systems (IEEE CBMS), Publisher: IEEE, Pages: 506-508, ISSN: 2372-9198

Conference paper

Moayyeri A, Patel R, Rodriguez MP, Denaxas S, Banerjee A, Allan V, Direk K, Prieto-Merino D, Asselbergs FW, Hingorani AD, Casas JP, Hemingway Het al., 2016, Low levels of LDL-cholesterol and incidence of a wide range of cardiovascular diseases: a linked electronic health records cohort of 550,000 people, Congress of the European-Society-of-Cardiology (ESC), Publisher: OXFORD UNIV PRESS, Pages: 1190-1191, ISSN: 0195-668X

Conference paper

Kenan D, 2016, Imaging of Wet Age-Related Macular Degeneration., Ann Neurosci, Vol: 23, ISSN: 0972-7531

Journal article

Direk K, Lau W, Small KS, Maniatis N, Andrew Tet al., 2014, ABCC5 Transporter is a Novel Type 2 Diabetes Susceptibility Gene in European and African American Populations, Annals of Human Genetics, Vol: 78, Pages: 333-344

Numerous functional studies have implicated PARL in relation to type 2 diabetes (T2D). We hypothesised that conflicting human association studies may be due to neighbouring causal variants being in linkage disequilibrium (LD) with PARL. We conducted a comprehensive candidate gene study of the extended LD genomic region that includes PARL and transporter ABCC5 using three data sets (two European and one African American), in relation to healthy glycaemic variation, visceral fat accumulation and T2D disease.We observed no evidence for previously reported T2D association with Val262Leu or PARL using array and fine-map genomic and expression data. By contrast, we observed strong evidence of T2D association with ABCC5 (intron 26) for European and African American samples (P = 3E−07) and with ABCC5 adipose expression in Europeans [odds ratio (OR) = 3.8, P = 2E−04]. The genomic location estimate for the ABCC5 functional variant, associated with all phenotypes and expression data (P = 1E−11), was identical for all samples (at Chr3q 185,136 kb B36), indicating that the risk variant is an expression quantitative trait locus (eQTL) with increased expression conferring risk of disease. That the association with T2D is observed in populations of disparate ancestry suggests the variant is a ubiquitous risk factor for T2D.

Journal article

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