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2. Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Author

Floyd, J S, Sitlani, C M, Avery, C L, Noordam, R, Li, X, Smith, A V, Gogarten, S M, Li, J, Broer, L, Evans, D S, Trompet, S, Brody, J A, Stewart, J D, Eicher, J D, Seyerle, A A, Roach, J, Lange, L A, Lin, H J, Kors, J A, Harris, T B, Li-Gao, R, Sattar, N, Cummings, S R, Wiggins, K L, Napier, M D, Stürmer, T, Bis, J C, Kerr, K F, Uitterlinden, A G, Taylor, K D, Stott, D J, de Mutsert, R, Launer, L J, Busch, E L, Méndez-Giráldez, R, Sotoodehnia, N, Soliman, E Z, Li, Y, Duan, Q, Rosendaal, F R, Slagboom, P E, Wilhelmsen, K C, Reiner, A P, Chen, Y-DI, Heckbert, S R, Kaplan, R C, Rice, K M, Jukema, J W, Johnson, A D, Liu, Y, Mook-Kanamori, D O, Gudnason, V, Wilson, J G, Rotter, J I, Laurie, C C, Psaty, B M, Whitsel, E A, Cupples, L A, and Stricker, B H

Published
2018
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4. Resting heart rate and incident atrial fibrillation:A stratified Mendelian randomization in the AFGen consortium

Author

Siland, J. E., Geelhoed, B., Roselli, C., Wang, B., Lin, H., Weiss, S., Trompet, S., van den Berg, M. E., Soliman, E. Z., Chen, L. Y., Ford, I., Jukema, J. W., Macfarlane, P. W., Kornej, J., Lunetta, K. L., Kavousi, M., Kors, J. A., Ikram, M. A., Guo, X., Yao, J., Dörr, M., Felix, S. B., Völker, U., Sotoodehnia, N., Arking, D. E., Stricker, B. H., Heckbert, S. R., Benjamin, E. J., Lubitz, S. A., Alonso, A., Ellinor, P. T., van der Harst, P., Rienstra, M., Siland, J. E., Geelhoed, B., Roselli, C., Wang, B., Lin, H., Weiss, S., Trompet, S., van den Berg, M. E., Soliman, E. Z., Chen, L. Y., Ford, I., Jukema, J. W., Macfarlane, P. W., Kornej, J., Lunetta, K. L., Kavousi, M., Kors, J. A., Ikram, M. A., Guo, X., Yao, J., Dörr, M., Felix, S. B., Völker, U., Sotoodehnia, N., Arking, D. E., Stricker, B. H., Heckbert, S. R., Benjamin, E. J., Lubitz, S. A., Alonso, A., Ellinor, P. T., van der Harst, P., and Rienstra, M.

Abstract

Background Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. Method and results Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65–75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94–0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. Conclusions For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

Published
2022

5. Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium

Author

Circulatory Health, Team Medisch, Siland, J E, Geelhoed, B, Roselli, C, Wang, B, Lin, H J, Weiss, S, Trompet, S, van den Berg, M E, Soliman, E Z, Chen, L Y, Ford, I, Jukema, J W, Macfarlane, P W, Kornej, J, Lin, H, Lunetta, K L, Kavousi, M, Kors, J A, Ikram, M A, Guo, X, Yao, J, Dörr, M, Felix, S B, Völker, U, Sotoodehnia, N, Arking, D E, Stricker, B H, Heckbert, S R, Lubitz, S A, Benjamin, E J, Alonso, A, Ellinor, P T, van der Harst, P, Rienstra, M, Circulatory Health, Team Medisch, Siland, J E, Geelhoed, B, Roselli, C, Wang, B, Lin, H J, Weiss, S, Trompet, S, van den Berg, M E, Soliman, E Z, Chen, L Y, Ford, I, Jukema, J W, Macfarlane, P W, Kornej, J, Lin, H, Lunetta, K L, Kavousi, M, Kors, J A, Ikram, M A, Guo, X, Yao, J, Dörr, M, Felix, S B, Völker, U, Sotoodehnia, N, Arking, D E, Stricker, B H, Heckbert, S R, Lubitz, S A, Benjamin, E J, Alonso, A, Ellinor, P T, van der Harst, P, and Rienstra, M

Published
2022

6. Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium

Author

Siland, J. E., primary, Geelhoed, B., additional, Roselli, C., additional, Wang, B., additional, Lin, H. J., additional, Weiss, S., additional, Trompet, S., additional, van den Berg, M. E., additional, Soliman, E. Z., additional, Chen, L. Y., additional, Ford, I., additional, Jukema, J. W., additional, Macfarlane, P. W., additional, Kornej, J., additional, Lin, H., additional, Lunetta, K. L., additional, Kavousi, M., additional, Kors, J. A., additional, Ikram, M. A., additional, Guo, X., additional, Yao, J., additional, Dörr, M., additional, Felix, S. B., additional, Völker, U., additional, Sotoodehnia, N., additional, Arking, D. E., additional, Stricker, B. H., additional, Heckbert, S. R., additional, Lubitz, S. A., additional, Benjamin, E. J., additional, Alonso, A., additional, Ellinor, P. T., additional, van der Harst, P., additional, and Rienstra, M., additional

Published
2022
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7. Drug–gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval

Author

Avery, C L, Sitlani, C M, Arking, D E, Arnett, D K, Bis, J C, Boerwinkle, E, Buckley, B M, Ida Chen, Y-D, de Craen, A J M, Eijgelsheim, M, Enquobahrie, D, Evans, D S, Ford, I, Garcia, M E, Gudnason, V, Harris, T B, Heckbert, S R, Hochner, H, Hofman, A, Hsueh, W-C, Isaacs, A, Jukema, J W, Knekt, P, Kors, J A, Krijthe, B P, Kristiansson, K, Laaksonen, M, Liu, Y, Li, X, MacFarlane, P W, Newton-Cheh, C, Nieminen, M S, Oostra, B A, Peloso, G M, Porthan, K, Rice, K, Rivadeneira, F F, Rotter, J I, Salomaa, V, Sattar, N, Siscovick, D S, Slagboom, P E, Smith, A V, Sotoodehnia, N, Stott, D J, Stricker, B H, Stürmer, T, Trompet, S, Uitterlinden, A G, van Duijn, C, Westendorp, R G J, Witteman, J C, Whitsel, E A, and Psaty, B M

Published
2014
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12. Obtaining EQ-5D-5L utilities from the disease specific quality of life Alzheimer’s disease scale: development and results from a mapping study

Author

Rombach, I., Iftikhar, M., Jhuti, G.S., Gustavsson, A., Lecomte, P., Belger, M., Handels, R., Castro Sanchez, A.Y., Kors, J., Hopper, L., Olde Rikkert, M., Selbæk, G., Stephan, A., Sikkes, S.A.M., Woods, B., Gonçalves-Pereira, M., Zanetti, O., Ramakers, I.H.G.B., Verhey, F.R.J., Gallacher, J., Actifcare Consortium, LeARN Consortium, Landeiro, F., Gray, A.M., and ROADMAP Consortium

Abstract

Purpose\ud \ud The Quality of Life Alzheimer’s Disease Scale (QoL-AD) is commonly used to assess disease specific health-related quality of life (HRQoL) as rated by patients and their carers. For cost-effectiveness analyses, utilities based on the EQ-5D are often required. We report a new mapping algorithm to obtain EQ-5D indices when only QoL-AD data are available.\ud \ud \ud \ud Methods\ud \ud Different statistical models to estimate utility directly, or responses to individual EQ-5D questions (response mapping) from QoL-AD, were trialled for patient-rated and proxy-rated questionnaires. Model performance was assessed by root mean square error and mean absolute error.\ud \ud \ud \ud Results\ud \ud The response model using multinomial regression including age and sex, performed best in both the estimation dataset and an independent dataset.\ud \ud \ud \ud Conclusions\ud \ud The recommended mapping algorithm allows researchers for the first time to estimate EQ-5D values from QoL-AD data, enabling cost-utility analyses using datasets where the QoL-AD but no utility measures were collected.

Published
2021

14. Seek COVER: Development and validation of a personalized risk calculator for COVID-19 outcomes in an international network

Author

Williams, R, Markus, A, Yang, C, Salles, TD, DuVall, S, Falconer, T, Jonnagaddala, J, Kim, C, Rho, Y, Williams, A, Alberga, A, An, MH, Aragón, M, Areia, C, Burn, E, Choi, YH, Drakos, I, Fernandes Abrahão, MT, Fernández-Bertolín, S, Hripcsak, G, Kaas-Hansen, BS, Kandukuri, P, Kors, J, Kostka, K, Liaw, S-T, Lynch, K, Machnicki, G, Matheny, M, Morales, D, Nyberg, F, Park, RW, Prats-Uribe, A, Pratt, N, Rao, G, Reich, C, Rivera, M, Seinen, T, Shoaibi, A, Spotnitz, M, Steyerberg, E, Suchard, M, You, SC, Zhang, L, Zhou, L, Ryan, P, Prieto-Alhambra, D, Reps, J, Rijnbeek, P, Williams, R, Markus, A, Yang, C, Salles, TD, DuVall, S, Falconer, T, Jonnagaddala, J, Kim, C, Rho, Y, Williams, A, Alberga, A, An, MH, Aragón, M, Areia, C, Burn, E, Choi, YH, Drakos, I, Fernandes Abrahão, MT, Fernández-Bertolín, S, Hripcsak, G, Kaas-Hansen, BS, Kandukuri, P, Kors, J, Kostka, K, Liaw, S-T, Lynch, K, Machnicki, G, Matheny, M, Morales, D, Nyberg, F, Park, RW, Prats-Uribe, A, Pratt, N, Rao, G, Reich, C, Rivera, M, Seinen, T, Shoaibi, A, Spotnitz, M, Steyerberg, E, Suchard, M, You, SC, Zhang, L, Zhou, L, Ryan, P, Prieto-Alhambra, D, Reps, J, and Rijnbeek, P

Abstract

Objective

To develop and externally validate COVID-19 Estimated Risk (COVER) scores that quantify a patient’s risk of hospital admission (COVER-H), requiring intensive services (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis.

Methods

We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries. We developed and validated 3 scores using 6,869,127 patients with a general practice, emergency room, or outpatient visit with diagnosed influenza or flu-like symptoms any time prior to 2020. The scores were validated on patients with confirmed or suspected COVID-19 diagnosis across five databases from South Korea, Spain and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death iii) death in the 30 days after index date.

Results

Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved high performance in influenza. When transported to COVID-19 cohorts, the AUC ranges were, COVER-H: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration was overall acceptable.

Conclusions

A 9-predictor model performs well for COVID-19 patients for predicting hospitalization, intensive services and fatality. The models could aid in providing reassurance for low risk patients and shield high risk patients from COVID-19 during de-confinement to reduce the virus’ impact on morbidity and mortality.

Published
2020

27. Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author

Nolte, I. M. (Ilja M.), Munoz, M. L. (M. Loretto), Tragante, V. (Vinicius), Amare, A. T. (Azmeraw T.), Jansen, R. (Rick), Vaez, A. (Ahmad), von der Heyde, B. (Benedikt), Avery, C. L. (Christy L.), Bis, J. C. (Joshua C.), Dierckx, B. (Bram), van Dongen, J. (Jenny), Gogarten, S. M. (Stephanie M.), Goyette, P. (Philippe), Hernesniemi, J. (Jussi), Huikari, V. (Ville), Hwang, S.-J. (Shih-Jen), Jaju, D. (Deepali), Kerr, K. F. (Kathleen F.), Kluttig, A. (Alexander), Krijthe, B. P. (Bouwe P.), Kumar, J. (Jitender), van der Laan, S. W. (Sander W.), Lyytikäinen, L.-P. (Leo-Pekka), Maihofer, A. X. (Adam X.), Minassian, A. (Arpi), van der Most, P. J. (Peter J.), Mueller-Nurasyid, M. (Martina), Nivard, M. (Michel), Salvi, E. (Erika), Stewart, J. D. (James D.), Thayer, J. F. (Julian F.), Verweij, N. (Niek), Wong, A. (Andrew), Zabaneh, D. (Delilah), Zafarmand, M. H. (Mohammad H.), Abdellaoui, A. (Abdel), Albarwani, S. (Sulayma), Albert, C. (Christine), Alonso, A. (Alvaro), Ashar, F. (Foram), Auvinen, J. (Juha), Axelsson, T. (Tomas), Baker, D. G. (Dewleen G.), de Bakker, P. I. (Paul I. W.), Barcella, M. (Matteo), Bayoumi, R. (Riad), Bieringa, R. J. (Rob J.), Boomsma, D. (Dorret), Boucher, G. (Gabrielle), Britton, A. R. (Annie R.), Christophersen, I. E. (Ingrid E.), Dietrich, A. (Andrea), Ehret, G. B. (George B.), Ellinor, P. T. (Patrick T.), Eskola, M. (Markku), Felix, J. F. (Janine F.), Floras, J. S. (John S.), Franco, O. H. (Oscar H.), Friberg, P. (Peter), Gademan, M. G. (Maaike G. J.), Geyer, M. A. (Mark A.), Giedraitis, V. (Vilmantas), Hartman, C. A. (Catharina A.), Hemerich, D. (Daiane), Hofman, A. (Albert), Hottenga, J.-J. (Jouke-Jan), Huikuri, H. (Heikki), Hutri-Kähönen, N. (Nina), Jouven, X. (Xavier), Junttila, J. (Juhani), Juonala, M. (Markus), Kiviniemi, A. M. (Antti M.), Kors, J. A. (Jan A.), Kumari, M. (Meena), Kuznetsova, T. (Tatiana), Laurie, C. C. (Cathy C.), Lefrandt, J. D. (Joop D.), Li, Y. (Yong), Li, Y. (Yun), Liao, D. (Duanping), Limacher, M. C. (Marian C.), Lin, H. J. (Henry J.), Lindgren, C. M. (Cecilia M.), Lubitz, S. A. (Steven A.), Mahajan, A. (Anubha), McKnight, B. (Barbara), zu Schwabedissen, H. M. (Henriette Meyer), Milaneschi, Y. (Yuri), Mononen, N. (Nina), Morris, A. P. (Andrew P.), Nalls, M. A. (Mike A.), Navis, G. (Gerjan), Neijts, M. (Melanie), Nikus, K. (Kjell), North, K. E. (Kari E.), O'Connor, D. T. (Daniel T.), Ormel, J. (Johan), Perz, S. (Siegfried), Peters, A. (Annette), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Risbrough, V. B. (Victoria B.), Sinner, M. F. (Moritz F.), Siscovick, D. (David), Smit, J. H. (Johannes H.), Smith, N. L. (Nicholas L.), Soliman, E. Z. (Elsayed Z.), Sotoodehnia, N. (Nona), Staessen, J. A. (Jan A.), Stein, P. K. (Phyllis K.), Stilp, A. M. (Adrienne M.), Stolarz-Skrzypek, K. (Katarzyna), Strauch, K. (Konstantin), Sundström, J. (Johan), Swenne, C. A. (Cees A.), Syvänen, A.-C. (Ann-Christine), Tardif, J.-C. (Jean-Claude), Taylor, K. D. (Kent D.), Teumer, A. (Alexander), Thornton, T. A. (Timothy A.), Tinker, L. E. (Lesley E.), Uitterlinden, A. G. (Andre G.), van Setten, J. (Jessica), Voss, A. (Andreas), Waldenberger, M. (Melanie), Wilhelmsen, K. C. (Kirk C.), Willemsen, G. (Gonneke), Wong, Q. (Quenna), Zhang, Z.-M. (Zhu-Ming), Zonderman, A. B. (Alan B.), Cusi, D. (Daniele), Evans, M. K. (Michele K.), Greiser, H. K. (Halina K.), van der Harst, P. (Pim), Hassan, M. (Mohammad), Ingelsson, E. (Erik), Järvelin, M.-R. (Marjo-Riitta), Kaab, S. (Stefan), Kähönen, M. (Mika), Kivimäki, M. (Mika), Kooperberg, C. (Charles), Kuh, D. (Diana), Lehtimäki, T. (Terho), Lind, L. (Lars), Nievergelt, C. M. (Caroline M.), O'Donnell, C. J. (Chris J.), Oldehinkel, A. J. (Albertine J.), Penninx, B. (Brenda), Reiner, A. P. (Alexander P.), Riese, H. (Harriette), van Roon, A. M. (Arie M.), Rioux, J. D. (John D.), Rotter, J. I. (Jerome I.), Sofer, T. (Tamar), Stricker, B. H. (Bruno H.), Tiemeier, H. (Henning), Vrijkotte, T. G. (Tanja G. M.), Asselbergs, F. W. (Folkert W.), Brundel, B. J. (Bianca J. J. M.), Heckbert, S. R. (Susan R.), Whitsel, E. A. (Eric A.), den Hoed, M. (Marcel), Snieder, H. (Harold), de Geus, E. J. (Eco J. C.), Nolte, I. M. (Ilja M.), Munoz, M. L. (M. Loretto), Tragante, V. (Vinicius), Amare, A. T. (Azmeraw T.), Jansen, R. (Rick), Vaez, A. (Ahmad), von der Heyde, B. (Benedikt), Avery, C. L. (Christy L.), Bis, J. C. (Joshua C.), Dierckx, B. (Bram), van Dongen, J. (Jenny), Gogarten, S. M. (Stephanie M.), Goyette, P. (Philippe), Hernesniemi, J. (Jussi), Huikari, V. (Ville), Hwang, S.-J. (Shih-Jen), Jaju, D. (Deepali), Kerr, K. F. (Kathleen F.), Kluttig, A. (Alexander), Krijthe, B. P. (Bouwe P.), Kumar, J. (Jitender), van der Laan, S. W. (Sander W.), Lyytikäinen, L.-P. (Leo-Pekka), Maihofer, A. X. (Adam X.), Minassian, A. (Arpi), van der Most, P. J. (Peter J.), Mueller-Nurasyid, M. (Martina), Nivard, M. (Michel), Salvi, E. (Erika), Stewart, J. D. (James D.), Thayer, J. F. (Julian F.), Verweij, N. (Niek), Wong, A. (Andrew), Zabaneh, D. (Delilah), Zafarmand, M. H. (Mohammad H.), Abdellaoui, A. (Abdel), Albarwani, S. (Sulayma), Albert, C. (Christine), Alonso, A. (Alvaro), Ashar, F. (Foram), Auvinen, J. (Juha), Axelsson, T. (Tomas), Baker, D. G. (Dewleen G.), de Bakker, P. I. (Paul I. W.), Barcella, M. (Matteo), Bayoumi, R. (Riad), Bieringa, R. J. (Rob J.), Boomsma, D. (Dorret), Boucher, G. (Gabrielle), Britton, A. R. (Annie R.), Christophersen, I. E. (Ingrid E.), Dietrich, A. (Andrea), Ehret, G. B. (George B.), Ellinor, P. T. (Patrick T.), Eskola, M. (Markku), Felix, J. F. (Janine F.), Floras, J. S. (John S.), Franco, O. H. (Oscar H.), Friberg, P. (Peter), Gademan, M. G. (Maaike G. J.), Geyer, M. A. (Mark A.), Giedraitis, V. (Vilmantas), Hartman, C. A. (Catharina A.), Hemerich, D. (Daiane), Hofman, A. (Albert), Hottenga, J.-J. (Jouke-Jan), Huikuri, H. (Heikki), Hutri-Kähönen, N. (Nina), Jouven, X. (Xavier), Junttila, J. (Juhani), Juonala, M. (Markus), Kiviniemi, A. M. (Antti M.), Kors, J. A. (Jan A.), Kumari, M. (Meena), Kuznetsova, T. (Tatiana), Laurie, C. C. (Cathy C.), Lefrandt, J. D. (Joop D.), Li, Y. (Yong), Li, Y. (Yun), Liao, D. (Duanping), Limacher, M. C. (Marian C.), Lin, H. J. (Henry J.), Lindgren, C. M. (Cecilia M.), Lubitz, S. A. (Steven A.), Mahajan, A. (Anubha), McKnight, B. (Barbara), zu Schwabedissen, H. M. (Henriette Meyer), Milaneschi, Y. (Yuri), Mononen, N. (Nina), Morris, A. P. (Andrew P.), Nalls, M. A. (Mike A.), Navis, G. (Gerjan), Neijts, M. (Melanie), Nikus, K. (Kjell), North, K. E. (Kari E.), O'Connor, D. T. (Daniel T.), Ormel, J. (Johan), Perz, S. (Siegfried), Peters, A. (Annette), Psaty, B. M. (Bruce M.), Raitakari, O. T. (Olli T.), Risbrough, V. B. (Victoria B.), Sinner, M. F. (Moritz F.), Siscovick, D. (David), Smit, J. H. (Johannes H.), Smith, N. L. (Nicholas L.), Soliman, E. Z. (Elsayed Z.), Sotoodehnia, N. (Nona), Staessen, J. A. (Jan A.), Stein, P. K. (Phyllis K.), Stilp, A. M. (Adrienne M.), Stolarz-Skrzypek, K. (Katarzyna), Strauch, K. (Konstantin), Sundström, J. (Johan), Swenne, C. A. (Cees A.), Syvänen, A.-C. (Ann-Christine), Tardif, J.-C. (Jean-Claude), Taylor, K. D. (Kent D.), Teumer, A. (Alexander), Thornton, T. A. (Timothy A.), Tinker, L. E. (Lesley E.), Uitterlinden, A. G. (Andre G.), van Setten, J. (Jessica), Voss, A. (Andreas), Waldenberger, M. (Melanie), Wilhelmsen, K. C. (Kirk C.), Willemsen, G. (Gonneke), Wong, Q. (Quenna), Zhang, Z.-M. (Zhu-Ming), Zonderman, A. B. (Alan B.), Cusi, D. (Daniele), Evans, M. K. (Michele K.), Greiser, H. K. (Halina K.), van der Harst, P. (Pim), Hassan, M. (Mohammad), Ingelsson, E. (Erik), Järvelin, M.-R. (Marjo-Riitta), Kaab, S. (Stefan), Kähönen, M. (Mika), Kivimäki, M. (Mika), Kooperberg, C. (Charles), Kuh, D. (Diana), Lehtimäki, T. (Terho), Lind, L. (Lars), Nievergelt, C. M. (Caroline M.), O'Donnell, C. J. (Chris J.), Oldehinkel, A. J. (Albertine J.), Penninx, B. (Brenda), Reiner, A. P. (Alexander P.), Riese, H. (Harriette), van Roon, A. M. (Arie M.), Rioux, J. D. (John D.), Rotter, J. I. (Jerome I.), Sofer, T. (Tamar), Stricker, B. H. (Bruno H.), Tiemeier, H. (Henning), Vrijkotte, T. G. (Tanja G. M.), Asselbergs, F. W. (Folkert W.), Brundel, B. J. (Bianca J. J. M.), Heckbert, S. R. (Susan R.), Whitsel, E. A. (Eric A.), den Hoed, M. (Marcel), Snieder, H. (Harold), and de Geus, E. J. (Eco J. C.)

Abstract

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74

Published
2017

28. Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology

Author

Seyerle, A A, primary, Sitlani, C M, additional, Noordam, R, additional, Gogarten, S M, additional, Li, J, additional, Li, X, additional, Evans, D S, additional, Sun, F, additional, Laaksonen, M A, additional, Isaacs, A, additional, Kristiansson, K, additional, Highland, H M, additional, Stewart, J D, additional, Harris, T B, additional, Trompet, S, additional, Bis, J C, additional, Peloso, G M, additional, Brody, J A, additional, Broer, L, additional, Busch, E L, additional, Duan, Q, additional, Stilp, A M, additional, O'Donnell, C J, additional, Macfarlane, P W, additional, Floyd, J S, additional, Kors, J A, additional, Lin, H J, additional, Li-Gao, R, additional, Sofer, T, additional, Méndez-Giráldez, R, additional, Cummings, S R, additional, Heckbert, S R, additional, Hofman, A, additional, Ford, I, additional, Li, Y, additional, Launer, L J, additional, Porthan, K, additional, Newton-Cheh, C, additional, Napier, M D, additional, Kerr, K F, additional, Reiner, A P, additional, Rice, K M, additional, Roach, J, additional, Buckley, B M, additional, Soliman, E Z, additional, de Mutsert, R, additional, Sotoodehnia, N, additional, Uitterlinden, A G, additional, North, K E, additional, Lee, C R, additional, Gudnason, V, additional, Stürmer, T, additional, Rosendaal, F R, additional, Taylor, K D, additional, Wiggins, K L, additional, Wilson, J G, additional, Chen, Y-DI, additional, Kaplan, R C, additional, Wilhelmsen, K, additional, Cupples, L A, additional, Salomaa, V, additional, van Duijn, C, additional, Jukema, J W, additional, Liu, Y, additional, Mook-Kanamori, D O, additional, Lange, L A, additional, Vasan, R S, additional, Smith, A V, additional, Stricker, B H, additional, Laurie, C C, additional, Rotter, J I, additional, Whitsel, E A, additional, Psaty, B M, additional, and Avery, C L, additional

Published
2017
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29. Triage and Evaluation of Potential Safety Signals Identified from Electronic Healthcare Record Databases

Author

Coloma, P, Schuemie, M, Trifiro, G, Furlong, L, Van Mulligen, E, Bauer-Mehren, A, Avillach, P, Kors, J, Sanz, F, Mestres, J, Oliveira, J, Boyer, S, Helgee, E, Molokhia, M, Matthews, J, Prieto-Merino, D, Gini, R, Herings, R, Mazzaglia, G, Picelli, G, Scotti, L, Pedetsen, L, Van der Lei, J, Sturkenboom, M, Coloma PM, Schuemie MJ, Trifiro G, Furlong L, Van Mulligen E, Bauer-Mehren A, Avillach P, Kors J, Sanz F, Mestres J, Oliveira JL, Boyer S, Helgee EA, Molokhia M, Matthews J, Prieto-Merino D, Gini R, Herings RMC, Mazzaglia G, Picelli G, Scotti L, Pedetsen L, Van der Lei J, Sturkenboom MCJM, Coloma, P, Schuemie, M, Trifiro, G, Furlong, L, Van Mulligen, E, Bauer-Mehren, A, Avillach, P, Kors, J, Sanz, F, Mestres, J, Oliveira, J, Boyer, S, Helgee, E, Molokhia, M, Matthews, J, Prieto-Merino, D, Gini, R, Herings, R, Mazzaglia, G, Picelli, G, Scotti, L, Pedetsen, L, Van der Lei, J, Sturkenboom, M, Coloma PM, Schuemie MJ, Trifiro G, Furlong L, Van Mulligen E, Bauer-Mehren A, Avillach P, Kors J, Sanz F, Mestres J, Oliveira JL, Boyer S, Helgee EA, Molokhia M, Matthews J, Prieto-Merino D, Gini R, Herings RMC, Mazzaglia G, Picelli G, Scotti L, Pedetsen L, Van der Lei J, and Sturkenboom MCJM

Abstract

Background: There is huge potential for mining electronic healthcare records (EHR) databases to augment current systems in pharmacovigilance.[1-3] Like any signal detection system, there is a need to establish ‘rules’ how to trigger an alert, when to consider a signal likely enough to be true to warrant follow-up or even to require immediate health policy intervention.[4,5] Objectives: To describe the process of prioritisation of drug-adverse event associations derived from signal detection using EHR databases in the EU-ADR Project. Methods: Association measures between drug use and acute myocardial infarction (AMI) were generated by first applying various statistical methods on healthcare data from seven databases of the EUADR network.[6] Association estimates were ranked based on the best performing method (Longitudinal Gamma Poisson Shrinker). Matched case-control and self-controlled case series methods were additionallyconducted to deal with temporality and confounding effect, while the LEOPARD method was applied to specifically detect protopathic bias. Consistency of the association among drugs of the same class and the number of excess cases attributable to the drug exposure were further assessed to prioritize the list of potential signals. Finally, signal filtering and signal substantiation were done using different bioinformatics workflows to determine the novelty and plausibility of the identified signals. Results: Demographic, clinical and prescription/dispensing data in three European Countries were obtained from 21 171 291 individuals with 154 474 063 person-years of follow-up within the period 1995–2011. Overall, 163 potential signals forAMI were identified based on statistical association. Of these, 72 signals were flagged by LEOPARDas likely due to protopathic bias. Further signal refinement to reduce possible confounding decreased the number of signals to 39. Nine signals remained after applying the criteria for novelty and plausibility. Conclusion

Published
2012

30. Large-scale pharmacogenomic study of sulfonylureas and the QT, JT and QRS intervals: CHARGE Pharmacogenomics Working Group

Author

Floyd, J S, primary, Sitlani, C M, additional, Avery, C L, additional, Noordam, R, additional, Li, X, additional, Smith, A V, additional, Gogarten, S M, additional, Li, J, additional, Broer, L, additional, Evans, D S, additional, Trompet, S, additional, Brody, J A, additional, Stewart, J D, additional, Eicher, J D, additional, Seyerle, A A, additional, Roach, J, additional, Lange, L A, additional, Lin, H J, additional, Kors, J A, additional, Harris, T B, additional, Li-Gao, R, additional, Sattar, N, additional, Cummings, S R, additional, Wiggins, K L, additional, Napier, M D, additional, Stürmer, T, additional, Bis, J C, additional, Kerr, K F, additional, Uitterlinden, A G, additional, Taylor, K D, additional, Stott, D J, additional, de Mutsert, R, additional, Launer, L J, additional, Busch, E L, additional, Méndez-Giráldez, R, additional, Sotoodehnia, N, additional, Soliman, E Z, additional, Li, Y, additional, Duan, Q, additional, Rosendaal, F R, additional, Slagboom, P E, additional, Wilhelmsen, K C, additional, Reiner, A P, additional, Chen, Y-DI, additional, Heckbert, S R, additional, Kaplan, R C, additional, Rice, K M, additional, Jukema, J W, additional, Johnson, A D, additional, Liu, Y, additional, Mook-Kanamori, D O, additional, Gudnason, V, additional, Wilson, J G, additional, Rotter, J I, additional, Laurie, C C, additional, Psaty, B M, additional, Whitsel, E A, additional, Cupples, L A, additional, and Stricker, B H, additional

Published
2016
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31. Drug–gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval

Author

Sitlani, C M, Arnett, D K, Liu, Y, Newton-Cheh, C, Arking, D E, Eijgelsheim, M, Evans, D S, Kristiansson, K, Nieminen, M S, Harris, T B, Hsueh, W-C, Laaksonen, M, Heckbert, S R, Bis, J C, Garcia, M E, Isaacs, A, Avery, C L, Jukema, J W, Gudnason, V, Knekt, P, Li, X, MacFarlane, P W, Kors, J A, Boerwinkle, E, Hochner, H, Ida Chen, Y-D, Enquobahrie, D, Buckley, B M, Krijthe, B P, Hofman, A, Ford, I, and de Craen, A J M

Abstract

Variability in response to drug use is common and heritable, suggesting that genome-wide pharmacogenomics studies may help explain the “missing heritability” of complex traits. Here, we describe four independent analyses in 33,781 participants of European ancestry from ten cohorts that were designed to identify genetic variants modifying the effects of drugs on QT interval duration (QT). Each analysis cross-sectionally examined four therapeutic classes: thiazide diuretics (prevalence of use=13.0%), tri/tetracyclic antidepressants (2.6%), sulfonylurea hypoglycemic agents (2.9%), and QT prolonging drugs as classified by the University of Arizona Center for Education and Research on Therapeutics (4.4%). Drug-gene interactions were estimated using covariable adjusted linear regression and results were combined with fixed-effects meta-analysis. Although drug-SNP interactions were biologically plausible and variables were well-measured, findings from the four cross-sectional meta-analyses were null (Pinteraction>5.0×10−8). Simulations suggested that additional efforts, including longitudinal modeling to increase statistical power, are likely needed to identify potentially important pharmacogenomic effects.

Published
2014
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32. SEMCARE - Semantic Data Platform for Healthcare

Author

Faßbender, T, Riede, C, Daumke, P, Honrado, A, Kreuzthaler, M, Lopez-Garcia, P, Schulz, S, van Mulligen, E, Kors, J, van Haagen, H, Gonna, H, Wang, X, Behr, E, Faßbender, T, Riede, C, Daumke, P, Honrado, A, Kreuzthaler, M, Lopez-Garcia, P, Schulz, S, van Mulligen, E, Kors, J, van Haagen, H, Gonna, H, Wang, X, and Behr, E

Published
2015

34. Drug-Induced Acute Myocardial Infarction: Identifying ‘Prime Suspects’ from Electronic Healthcare Records-Based Surveillance System

Author

Pm, Coloma, Mj, Schuemie, Trifirò G, Furlong L, Erik van Mulligen, Bauer-Mehren A, Avillach P, Kors J, Sanz F, Mestres J, Jl, Oliveira, Boyer S, Ea, Helgee, Molokhia M, Matthews J, Prieto-Merino D, Gini R, Herings R, Mazzaglia G, Picelli G, Scotti L, Pedersen L, van der Lei J, and Sturkenboom M

Subjects
Multidisciplinary, lcsh:R, Correction, lcsh:Medicine, lcsh:Q, lcsh:Science
Published
2013

35. Genome-wide association analysis identifies multiple loci related to resting heart rate

Author

Sotoodehnia, N., Eijgelsheim, M., Muller, M., Newton-Cheh, C., Navarro, P., Spector, T. D., Rivadeneira, F., Hottenga, J. J., de Bakker, P. I. W., Perz, S., Hwang, S.-J., Fuchsberger, C., Nolte, I. M., de Geus, E. J. C., Noseworthy, P. A., Ruckert, I.-M., Morrison, A. C., Sanna, S., Isaacs, A., Arking, D. E., Estrada, K., Bis, J. C., Tarasov, K. V., Alonso, A., Aulchenko, Y. S., Wild, S. H., Smith, A. V., Rice, K. M., Dorr, M., Kors, J. A., Launer, L. J., and Homuth, G.

Abstract

Higher resting heart rate is associated with increased cardiovascular disease and mortality risk. Though heritable factors play a substantial role in population variation, little is known about specific genetic determinants. This knowledge can impact clinical care by identifying novel factors that influence pathologic heart rate states, modulate heart rate through cardiac structure and function or by improving our understanding of the physiology of heart rate regulation. To identify common genetic variants associated with heart rate, we performed a meta-analysis of 15 genome-wide association studies (GWAS), including 38 991 subjects of European ancestry, estimating the association between age-, sex- and body mass-adjusted RR interval (inverse heart rate) and ∼2.5 million markers. Results with P < 5 × 10−8 were considered genome-wide significant. We constructed regression models with multiple markers to assess whether results at less stringent thresholds were likely to be truly associated with RR interval. We identified six novel associations with resting heart rate at six loci: 6q22 near GJA1; 14q12 near MYH7; 12p12 near SOX5, c12orf67, BCAT1, LRMP and CASC1; 6q22 near SLC35F1, PLN and c6orf204; 7q22 near SLC12A9 and UfSp1; and 11q12 near FADS1. Associations at 6q22 400 kb away from GJA1, at 14q12 MYH6 and at 1q32 near CD34 identified in previously published GWAS were confirmed. In aggregate, these variants explain ∼0.7% of RR interval variance. A multivariant regression model including 20 variants with P < 10−5 increased the explained variance to 1.6%, suggesting that some loci falling short of genome-wide significance are likely truly associated. Future research is warranted to elucidate underlying mechanisms that may impact clinical care.

Published
2010
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36. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author

Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, DE, Pulit, SL, Munroe, PB, Rossin, EJ, Johnson, AD, Gudbjartsson, DF, Noseworthy, PA, Tarasov, KV, Lahtinen, AM, Nolte, IM, Smith, AV, Bis, JC, Newhouse, SJ, Evans, DS, Post, WS, Lyytikäinen, LP, Hicks, AA, Tester, DJ, Morris, RW, Naluai, AT, Panayiotou, AG, Hubacek, JA, Kumar, RD, Harris, TB, Launer, LJ, Shuldiner, AR, Bader, JS, Kao, WH, Strait, JB, Macfarlane, PW, Caulfield, MJ, Samani, NJ, Smith, JG, Greiser, KH, Heckbert, SR, Psaty, BM, Rotter, JI, Wright, AF, Daly, MJ, Arnar, DO, Denny, JC, Roden, DM, Zuvich, RL, Plump, AS, Larson, MG, O'Donnell, CJ, D'Adamo, AP, Cummings, SR, Nalls, MA, Kontula, KK, Jöckel, KH, Nöthen, MM, Loos, RJ, Thelle, DS, Sinner, MF, de Boer, RA, van der Vleuten, PA, Beckmann, BM, Wilde, AA, Behr, ER, Giudicessi, JR, Hamilton, RM, Scherer, SW, Moravec, CE, Greco, MFD, O'Connell, JR, Lee, WK, Watt, GC, Wild, SH, El Mokhtari, NE, Asselbergs, FW, van den Berg, MP, van Veldhuisen, DJ, Krijthe, BP, Franco, OH, Kors, JA, Uitterlinden, AG, Witteman, JC, Oostra, BA, Abecasis, GR, Lakatta, EG, Markus, MR, Spector, TD, Syvänen, AC, Raitakari, OT, Viikari, JS, Nicolaides, AN, Dominiczak, AF, Whincup, PH, Hingorani, AD, Schott, JJ, Bezzina, CR, Wilson, JF, Mühleisen, TW, Pramstaller, PP, Lehtimäki, TJ, Paterson, AD, van Duijn, CM, Siscovick, DS, Felix, SB, Ritchie, MD, Stricker, BH, Boyer, LA, Cappola, TP, Olsen, JV, Schwartz, PJ, Ackerman, MJ, de Bakker, PI, Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, DE, Pulit, SL, Munroe, PB, Rossin, EJ, Johnson, AD, Gudbjartsson, DF, Noseworthy, PA, Tarasov, KV, Lahtinen, AM, Nolte, IM, Smith, AV, Bis, JC, Newhouse, SJ, Evans, DS, Post, WS, Lyytikäinen, LP, Hicks, AA, Tester, DJ, Morris, RW, Naluai, AT, Panayiotou, AG, Hubacek, JA, Kumar, RD, Harris, TB, Launer, LJ, Shuldiner, AR, Bader, JS, Kao, WH, Strait, JB, Macfarlane, PW, Caulfield, MJ, Samani, NJ, Smith, JG, Greiser, KH, Heckbert, SR, Psaty, BM, Rotter, JI, Wright, AF, Daly, MJ, Arnar, DO, Denny, JC, Roden, DM, Zuvich, RL, Plump, AS, Larson, MG, O'Donnell, CJ, D'Adamo, AP, Cummings, SR, Nalls, MA, Kontula, KK, Jöckel, KH, Nöthen, MM, Loos, RJ, Thelle, DS, Sinner, MF, de Boer, RA, van der Vleuten, PA, Beckmann, BM, Wilde, AA, Behr, ER, Giudicessi, JR, Hamilton, RM, Scherer, SW, Moravec, CE, Greco, MFD, O'Connell, JR, Lee, WK, Watt, GC, Wild, SH, El Mokhtari, NE, Asselbergs, FW, van den Berg, MP, van Veldhuisen, DJ, Krijthe, BP, Franco, OH, Kors, JA, Uitterlinden, AG, Witteman, JC, Oostra, BA, Abecasis, GR, Lakatta, EG, Markus, MR, Spector, TD, Syvänen, AC, Raitakari, OT, Viikari, JS, Nicolaides, AN, Dominiczak, AF, Whincup, PH, Hingorani, AD, Schott, JJ, Bezzina, CR, Wilson, JF, Mühleisen, TW, Pramstaller, PP, Lehtimäki, TJ, Paterson, AD, van Duijn, CM, Siscovick, DS, Felix, SB, Ritchie, MD, Stricker, BH, Boyer, LA, Cappola, TP, Olsen, JV, Schwartz, PJ, Ackerman, MJ, and de Bakker, PI

Abstract

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Published
2014

38. Drug-Induced Acute Myocardial Infarction: Identifying 'Prime Suspects' from Electronic Healthcare Records-Based Surveillance System

Author

Coloma, P, Schuemie, M, Trifirò, G, Furlong, L, van Mulligen, E, Bauer Mehren, A, Avillach, P, Kors, J, Sanz, F, Mestres, J, Oliveira, J, Boyer, S, Helgee, E, Molokhia, M, Matthews, J, Prieto Merino, D, Gini, R, Herings, R, Mazzaglia, G, Picelli, G, Scotti, L, Pedersen, L, van der Lei, J, Sturkenboom, M, Sturkenboom, M., SCOTTI, LORENZA, Coloma, P, Schuemie, M, Trifirò, G, Furlong, L, van Mulligen, E, Bauer Mehren, A, Avillach, P, Kors, J, Sanz, F, Mestres, J, Oliveira, J, Boyer, S, Helgee, E, Molokhia, M, Matthews, J, Prieto Merino, D, Gini, R, Herings, R, Mazzaglia, G, Picelli, G, Scotti, L, Pedersen, L, van der Lei, J, Sturkenboom, M, Sturkenboom, M., and SCOTTI, LORENZA

Abstract

Background:Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in 'real-world' settings.Objective:To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network.Methods:Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996-2010. Primary care physicians' medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible.Results:Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs ('prime suspects'): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate.Limitations:Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out.Conclusion:A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that

Published
2013

39. Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology

Author

Seyerle, A A, Sitlani, C M, Noordam, R, Gogarten, S M, Li, J, Li, X, Evans, D S, Sun, F, Laaksonen, M A, Isaacs, A, Kristiansson, K, Highland, H M, Stewart, J D, Harris, T B, Trompet, S, Bis, J C, Peloso, G M, Brody, J A, Broer, L, Busch, E L, Duan, Q, Stilp, A M, O'Donnell, C J, Macfarlane, P W, Floyd, J S, Kors, J A, Lin, H J, Li-Gao, R, Sofer, T, Méndez-Giráldez, R, Cummings, S R, Heckbert, S R, Hofman, A, Ford, I, Li, Y, Launer, L J, Porthan, K, Newton-Cheh, C, Napier, M D, Kerr, K F, Reiner, A P, Rice, K M, Roach, J, Buckley, B M, Soliman, E Z, de Mutsert, R, Sotoodehnia, N, Uitterlinden, A G, North, K E, Lee, C R, Gudnason, V, Stürmer, T, Rosendaal, F R, Taylor, K D, Wiggins, K L, Wilson, J G, Chen, Y-DI, Kaplan, R C, Wilhelmsen, K, Cupples, L A, Salomaa, V, van Duijn, C, Jukema, J W, Liu, Y, Mook-Kanamori, D O, Lange, L A, Vasan, R S, Smith, A V, Stricker, B H, Laurie, C C, Rotter, J I, Whitsel, E A, Psaty, B M, and Avery, C L

Abstract

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78?199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide–SNP interactions.

Published
2018
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40. Assessment of NER solutions against the first and second CALBC Silver Standard Corpus.

Author

Rebholz-Schuhmann, D, Jimeno Yepes, A, Li, C, Kafkas, S, Lewin, I, Kang, N, Corbett, P, Milward, D, Buyko, E, Beisswanger, E, Hornbostel, K, Kouznetsov, A, Witte, R, Laurila, JB, Baker, CJ, Kuo, C-J, Clematide, S, Rinaldi, F, Farkas, R, Móra, G, Hara, K, Furlong, LI, Rautschka, M, Neves, ML, Pascual-Montano, A, Wei, Q, Collier, N, Chowdhury, MFM, Lavelli, A, Berlanga, R, Morante, R, Van Asch, V, Daelemans, W, Marina, JL, van Mulligen, E, Kors, J, Hahn, U, Rebholz-Schuhmann, D, Jimeno Yepes, A, Li, C, Kafkas, S, Lewin, I, Kang, N, Corbett, P, Milward, D, Buyko, E, Beisswanger, E, Hornbostel, K, Kouznetsov, A, Witte, R, Laurila, JB, Baker, CJ, Kuo, C-J, Clematide, S, Rinaldi, F, Farkas, R, Móra, G, Hara, K, Furlong, LI, Rautschka, M, Neves, ML, Pascual-Montano, A, Wei, Q, Collier, N, Chowdhury, MFM, Lavelli, A, Berlanga, R, Morante, R, Van Asch, V, Daelemans, W, Marina, JL, van Mulligen, E, Kors, J, and Hahn, U

Abstract

BACKGROUND: Competitions in text mining have been used to measure the performance of automatic text processing solutions against a manually annotated gold standard corpus (GSC). The preparation of the GSC is time-consuming and costly and the final corpus consists at the most of a few thousand documents annotated with a limited set of semantic groups. To overcome these shortcomings, the CALBC project partners (PPs) have produced a large-scale annotated biomedical corpus with four different semantic groups through the harmonisation of annotations from automatic text mining solutions, the first version of the Silver Standard Corpus (SSC-I). The four semantic groups are chemical entities and drugs (CHED), genes and proteins (PRGE), diseases and disorders (DISO) and species (SPE). This corpus has been used for the First CALBC Challenge asking the participants to annotate the corpus with their text processing solutions. RESULTS: All four PPs from the CALBC project and in addition, 12 challenge participants (CPs) contributed annotated data sets for an evaluation against the SSC-I. CPs could ignore the training data and deliver the annotations from their genuine annotation system, or could train a machine-learning approach on the provided pre-annotated data. In general, the performances of the annotation solutions were lower for entities from the categories CHED and PRGE in comparison to the identification of entities categorized as DISO and SPE. The best performance over all semantic groups were achieved from two annotation solutions that have been trained on the SSC-I.The data sets from participants were used to generate the harmonised Silver Standard Corpus II (SSC-II), if the participant did not make use of the annotated data set from the SSC-I for training purposes. The performances of the participants' solutions were again measured against the SSC-II. The performances of the annotation solutions showed again better results for DISO and SPE in comparison to CHED and PR

Published
2011

41. Psychotropic drugs associated with corrected QT interval prolongation

Author

van Noord, C, Straus, S, Sturkenboom, M, Hofman, A, Aarnoudse, A, Bagnardi, V, Kors, J, Newton Cheh, C, Witteman, J, Stricker, B, Straus, SM, Sturkenboom, MC, Aarnoudse, AJ, Kors, JA, Witteman, JC, Stricker BH, BAGNARDI, VINCENZO, van Noord, C, Straus, S, Sturkenboom, M, Hofman, A, Aarnoudse, A, Bagnardi, V, Kors, J, Newton Cheh, C, Witteman, J, Stricker, B, Straus, SM, Sturkenboom, MC, Aarnoudse, AJ, Kors, JA, Witteman, JC, Stricker BH, and BAGNARDI, VINCENZO

Abstract

AIMS: To study whether listed putative corrected QT (QTc)-prolonging psychotropic drugs indeed prolong the QTc interval under everyday circumstances and to evaluate whether this is a class effect or an individual drug effect, we conducted a prospective population-based cohort study. METHODS: This study was conducted as part of the Rotterdam Study and included 3377 men and 4845 women (>or=55 years) who had triennial electrocardiograms (ECGs). The primary end points of the study were the length of the QTc interval at each ECG, the difference in QTc interval between consecutive ECGs within one person, and the risk of an abnormally prolonged QTc interval. Drug use at the index date was obtained from automated dispensing records. The associations were examined by means of a repeated measurement analysis, adjusted for age, sex, diabetes mellitus, hypertension, myocardial infarction, heart failure, and use of class 1 QTc-prolonging drugs. RESULTS: Of the 8222 participants, 813 participants (9.9%) developed QTc prolongation during follow-up and 492 participants (74.4% women) used psychotropic drugs at the time of an ECG. Starting tricyclic antidepressants increased the QTc interval significantly with 6.9 milliseconds (95% confidence interval [CI], 3.1-10.7 milliseconds) between consecutive ECGs in comparison with consecutive ECGs of participants not using tricyclic antidepressants, in particular starting amitriptyline (8.5 milliseconds; 95% CI, 2.8-14.2 milliseconds), maprotiline (13.9 milliseconds; 95% CI, 3.6-24.3 milliseconds), and nortriptyline (35.3 milliseconds; 95% CI, 8.0-62.6 milliseconds). Starting lithium also increased the QTc interval significantly (18.6 milliseconds; 95% CI, 4.8-32.4 milliseconds). CONCLUSIONS: In this population-based prospective cohort study, we confirmed the importance of antidepressants and antipsychotics as potential contributors to QTc prolongation. Especially, starting tricyclic antidepressant drugs (as a class) is associated with a sig

Published
2009

43. Drug–gene interactions and the search for missing heritability: a cross-sectional pharmacogenomics study of the QT interval

Author

Avery, C L, primary, Sitlani, C M, additional, Arking, D E, additional, Arnett, D K, additional, Bis, J C, additional, Boerwinkle, E, additional, Buckley, B M, additional, Ida Chen, Y-D, additional, de Craen, A J M, additional, Eijgelsheim, M, additional, Enquobahrie, D, additional, Evans, D S, additional, Ford, I, additional, Garcia, M E, additional, Gudnason, V, additional, Harris, T B, additional, Heckbert, S R, additional, Hochner, H, additional, Hofman, A, additional, Hsueh, W-C, additional, Isaacs, A, additional, Jukema, J W, additional, Knekt, P, additional, Kors, J A, additional, Krijthe, B P, additional, Kristiansson, K, additional, Laaksonen, M, additional, Liu, Y, additional, Li, X, additional, MacFarlane, P W, additional, Newton-Cheh, C, additional, Nieminen, M S, additional, Oostra, B A, additional, Peloso, G M, additional, Porthan, K, additional, Rice, K, additional, Rivadeneira, F F, additional, Rotter, J I, additional, Salomaa, V, additional, Sattar, N, additional, Siscovick, D S, additional, Slagboom, P E, additional, Smith, A V, additional, Sotoodehnia, N, additional, Stott, D J, additional, Stricker, B H, additional, Stürmer, T, additional, Trompet, S, additional, Uitterlinden, A G, additional, van Duijn, C, additional, Westendorp, R G J, additional, Witteman, J C, additional, Whitsel, E A, additional, and Psaty, B M, additional

Published
2013
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44. Antidepressants and heart-rate variability in older adults: a population-based study.

Author

Noordam, R., van den Berg, M. E., Niemeijer, M. N., Aarts, N., Hofman, A., Tiemeier, H., Kors, J. A., Stricker, B. H., Eijgelsheim, M., Visser, L. E., and Rijnbeek, P. R.

Subjects
ANTIDEPRESSANTS, ELECTROCARDIOGRAPHY, EPIDEMIOLOGY, HEART beat, PUBLIC health surveillance, SEROTONIN uptake inhibitors
Abstract

BackgroundTricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study.MethodIn the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991–2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs.ResultsWe included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes.ConclusionTCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors. [ABSTRACT FROM PUBLISHER]

Published
2016
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45. Cardiovascular complications in CKD 5D

Author

Fusaro, M., primary, Fusaro, M., additional, Noale, M., additional, Tripepi, G., additional, D'angelo, A., additional, Miozzo, D., additional, Gallieni, M., additional, Study Group, P.-V., additional, Tsamelesvili, M., additional, Dimitriadis, C., additional, Papagianni, A., additional, Raidis, C., additional, Efstratiadis, G., additional, Memmos, D., additional, Mutluay, R., additional, Konca Degertekin, C., additional, Derici, U., additional, Deger, S. M., additional, Akkiyal, F., additional, Gultekin, S., additional, Gonen, S., additional, Tacoy, G., additional, Arinsoy, T., additional, Sindel, S., additional, Sanchez-Perales, C., additional, Vazquez, E., additional, Merino, E., additional, Perez Del Barrio, P., additional, Borrego, F. J., additional, Borrego, M. J., additional, Liebana, A., additional, Krzanowski, M., additional, Janda, K., additional, Dumnicka, P., additional, Krasniak, A., additional, Sulowicz, W., additional, Kim, Y.-O., additional, Yoon, S.-A., additional, Yun, Y.-S., additional, Song, H.-C., additional, Kim, B.-S., additional, Cheong, M. A., additional, Pasch, A., additional, Farese, S., additional, Floege, J., additional, Jahnen-Dechent, W., additional, Ohtake, T., additional, Furuya, R., additional, Iwagami, M., additional, Tsutsumi, D., additional, Mochida, Y., additional, Ishioka, K., additional, Oka, M., additional, Maesato, K., additional, Moriya, H., additional, Hidaka, S., additional, Kobayashi, S., additional, Guedes, A., additional, Malho Guedes, A., additional, Pinho, A., additional, Fragoso, A., additional, Cruz, A., additional, Mendes, P., additional, Morgado, E., additional, Bexiga, I., additional, Silva, A. P., additional, Neves, P., additional, Oyake, N., additional, Suzuki, K., additional, Itoh, S., additional, Yano, S., additional, Turkmen, K., additional, Kayikcioglu, H., additional, Ozbek, O., additional, Saglam, M., additional, Toker, A., additional, Tonbul, H. Z., additional, Gelev, S., additional, Trajceska, L., additional, Srbinovska, E., additional, Pavleska, S., additional, Amitov, V., additional, Selim, G., additional, Dzekova, P., additional, Sikole, A., additional, Bouarich, H., additional, Lopez, S., additional, Alvarez, C., additional, Arribas, I., additional, DE Sequera, P., additional, Rodriguez, D., additional, Tanaka, S., additional, Kanemitsu, T., additional, Sugahara, M., additional, Kobayashi, M., additional, Uchida, L., additional, Ishimoto, Y., additional, Kotera, N., additional, Tanimoto, S., additional, Tanabe, K., additional, Hara, K., additional, Sugimoto, T., additional, Mise, N., additional, Goldstein, B., additional, Turakhia, M., additional, Arce, C., additional, Winkelmayer, W., additional, Zayed, B. E.-D., additional, Said, K., additional, Nishimura, M., additional, Okamoto, Y., additional, Tokoro, T., additional, Nishida, M., additional, Hashimoto, T., additional, Iwamoto, N., additional, Takahashi, H., additional, Ono, T., additional, Sato, N., additional, Raimann, J., additional, Usvyat, L. A., additional, Sands, J., additional, Levin, N. W., additional, Kotanko, P., additional, Iwasaki, M., additional, Joki, N., additional, Tanaka, Y., additional, Ikeda, N., additional, Hayashi, T., additional, Kubo, S., additional, Imamura, T.-A., additional, Takahashi, Y., additional, Hirahata, K., additional, Imamura, Y., additional, Hase, H., additional, Claes, K., additional, Meijers, B., additional, Bammens, B., additional, Kuypers, D., additional, Naesens, M., additional, Vanrenterghem, Y., additional, Evenepoel, P., additional, Boscutti, G., additional, Calabresi, L., additional, Bosco, M., additional, Simonelli, S., additional, Boer, E., additional, Vitali, C., additional, Martone, M., additional, Mattei, P. L., additional, Franceschini, G., additional, Baligh, E., additional, El-Shafey, E., additional, Ezaat, A., additional, Zawada, A., additional, Rogacev, K., additional, Hummel, B., additional, Grun, O., additional, Friedrich, A., additional, Rotter, B., additional, Winter, P., additional, Geisel, J., additional, Fliser, D., additional, Heine, G. H., additional, Makino, J.-I., additional, Makino, K.-S., additional, Ito, T., additional, Genovesi, S., additional, Santoro, A., additional, Fabbrini, P., additional, Rossi, E., additional, Pogliani, D., additional, Stella, A., additional, Bonforte, G., additional, Remuzzi, G., additional, Bertoli, S., additional, Pozzi, C., additional, Pasquali, S., additional, Cagnoli, L., additional, Conte, F., additional, Buzadzic, I., additional, Tosic, J., additional, Dimkovic, N., additional, Djuric, Z., additional, Popovic, J., additional, Pejin Grubisa, I., additional, Barjaktarevic, N., additional, DI Napoli, A., additional, DI Lallo, D., additional, Salvatori, M. F., additional, Franco, F., additional, Chicca, S., additional, Guasticchi, G., additional, Onofriescu, M., additional, Hogas, S., additional, Luminita, V., additional, Mugurel, A., additional, Gabriel, V., additional, Laura, F., additional, Irina, M., additional, Adrian, C., additional, Bosch, E., additional, Baamonde, E., additional, Culebras, C., additional, Perez, G., additional, El Hayek, B., additional, Ramirez, J. I., additional, Ramirez, A., additional, Garcia, C., additional, Lago, M., additional, Toledo, A., additional, Checa, M. D., additional, Taira, T., additional, Hirano, T., additional, Nohtomi, K., additional, Hyodo, T., additional, Chiba, T., additional, Saito, A., additional, Kim, Y. K., additional, Choi, E. J., additional, Yang, C. W., additional, Kim, Y.-S., additional, Lim, P. S., additional, Ming Ying, W., additional, Ya-Chung, J., additional, Zaripova, I., additional, Kayukov, I., additional, Essaian, A., additional, Nimgirova, A., additional, Young, H., additional, Dungey, M., additional, Watson, E. L., additional, Baines, R., additional, Burton, J. O., additional, Smith, A. C., additional, Yamazaki, K., additional, Bossola, M., additional, Colacicco, L., additional, Scribano, D., additional, Vulpio, C., additional, Tazza, L., additional, Okada, T., additional, Okada, N., additional, Michibata, I., additional, Yura, T., additional, Montero, N., additional, Soler, M., additional, Pascual, M., additional, Barrios, C., additional, Marquez, E., additional, Rodriguez, E., additional, Orfila, M. A., additional, Cao, H., additional, Arcos, E., additional, Comas, J., additional, Pascual, J., additional, Ferrario, M., additional, Garzotto, F., additional, Sironi, T., additional, Monacizzo, S., additional, Basso, F., additional, Cruz, D. N., additional, Moissl, U., additional, Tetta, C., additional, Signorini, M. G., additional, Cerutti, S., additional, Ronco, C., additional, Mostovaya, I., additional, Grooteman, M., additional, Van den Dorpel, M., additional, Penne, L., additional, Van der Weerd, N., additional, Mazairac, A., additional, Den Hoedt, C., additional, Levesque, R., additional, Nube, M., additional, Ter Wee, P., additional, Bots, M., additional, Blankestijn, P., additional, Liu, J., additional, MA, K. L., additional, Zhang, X., additional, Liu, B. C., additional, Vladu, I.-D., additional, Mustafa, R., additional, Cana-Ruiu, D., additional, Vaduva, C., additional, Grauntanu, C., additional, Mota, E., additional, Singh, R., additional, Abbasian, N., additional, Stover, C., additional, Brunskill, N., additional, Burton, J., additional, Herbert, K., additional, Bevington, A., additional, Wu, M., additional, Tang, R.-N., additional, Gao, M., additional, Liu, H., additional, Chen, L., additional, LV, L.-L., additional, Liu, B.-C., additional, Nikodimopoulou, M., additional, Liakos, S., additional, Kapoulas, S., additional, Karvounis, C., additional, Fedak, D., additional, Kuzniewski, M., additional, Paulina, D., additional, Kusnierz-Cabala, B., additional, Kapusta, M., additional, Solnica, B., additional, Junque, A., additional, Vicent, E. S., additional, Moreno, L., additional, Fulquet, M., additional, Duarte, V., additional, Saurina, A., additional, Pou, M., additional, Macias, J., additional, Lavado, M., additional, Ramirez de Arellano, M., additional, Ryuzaki, M., additional, Nakamoto, H., additional, Kinoshita, S., additional, Kobayashi, E., additional, Takimoto, C., additional, Shishido, T., additional, Enia, G., additional, Torino, C., additional, Tripepi, R., additional, Panuccio, V., additional, Postorino, M., additional, Clementi, A., additional, Garozzo, M., additional, Bonanno, G., additional, Boito, R., additional, Natale, G., additional, Cicchetti, T., additional, Chippari, A., additional, Logozzo, D., additional, Alati, G., additional, Cassani, S., additional, Sellaro, A., additional, Zoccali, C., additional, Quiroga, B., additional, Verde, E., additional, Abad, S., additional, Vega, A., additional, Goicoechea, M., additional, Reque, J., additional, Lopez-Gomez, J. M., additional, Luno, J., additional, Cabre Menendez, C., additional, Moles, V., additional, Vives, J. P., additional, Villa, D., additional, Vinas, J., additional, Compte, T., additional, Arruche, M., additional, Diaz, C., additional, Soler, J., additional, Aguilera, J., additional, Martinez Vea, A., additional, De Mauri, A., additional, David, P., additional, Conte, M. M., additional, Chiarinotti, D., additional, Ruva, C. E., additional, De Leo, M., additional, Bargnoux, A.-S., additional, Morena, M., additional, Jaussent, I., additional, Chalabi, L., additional, Bories, P., additional, Dion, J.-J., additional, Henri, P., additional, Delage, M., additional, Dupuy, A.-M., additional, Badiou, S., additional, Canaud, B., additional, Cristol, J.-P., additional, Sironi, E., additional, Pieruzzi, F., additional, Galbiati, E., additional, Vigano, M. R., additional, Anpalakhan, S., additional, Rocha, S., additional, Chitalia, N., additional, Sharma, R., additional, Kaski, J. C., additional, Chambers, J., additional, Goldsmith, D., additional, Banerjee, D., additional, Cernaro, V., additional, Lacquaniti, A., additional, Lupica, R., additional, Lucisano, S., additional, Fazio, M. R., additional, Donato, V., additional, Buemi, M., additional, Segalen, I., additional, Vinsonneau, U., additional, Tanquerel, T., additional, Quiniou, G., additional, Le Meur, Y., additional, Seibert, E., additional, Girndt, M., additional, Zohles, K., additional, Ulrich, C., additional, Kluttig, A., additional, Nuding, S., additional, Swenne, C., additional, Kors, J., additional, Werdan, K., additional, Fiedler, R., additional, Van der Weerd, N. C., additional, Grooteman, M. P., additional, Van den Dorpel, M. A., additional, Nube, M. J., additional, Wetzels, J., additional, Swinkels, D. W., additional, Ter Wee, P. M., additional, Khandekar, A., additional, Khandge, J., additional, Lee, J. E., additional, Moon, S. J., additional, Choi, K. H., additional, Lee, H. Y., additional, Kim, B. S., additional, Tuaillon, E., additional, Rodriguez, A., additional, Chenine, L., additional, Vendrell, J.-P., additional, Sue, Y.-M., additional, Tang, C.-H., additional, Chen, Y.-C., additional, Segura, P., additional, Garcia Cortes, M. J., additional, Gil, J. M., additional, Biechy, M. M., additional, Poulikakos, D., additional, Shah, A., additional, Persson, M., additional, Dattolo, P., additional, Amidone, M., additional, Michelassi, S., additional, Moriconi, L., additional, Betti, G., additional, Conti, P., additional, Rosati, A., additional, Mannarino, A., additional, Panichi, V., additional, Pizzarelli, F., additional, Klejna, K., additional, Naumnik, B., additional, Koc-Zorawska, E., additional, Mysliwiec, M., additional, Dimitrie, S., additional, Simona, H., additional, Mihaela, O., additional, Gabriela, O., additional, Radu, S., additional, Octavian, P., additional, Akdam, H., additional, Akar, H., additional, Yenicerioglu, Y., additional, Kucuk, O., additional, Kurt Omurlu, I., additional, Thambiah, S., additional, Roplekar, R., additional, Manghat, P., additional, Fogelman, I., additional, Fraser, W., additional, Hampson, G., additional, Likaj, E., additional, Caco, G., additional, Seferi, S., additional, Rroji, M., additional, Barbullushi, M., additional, Thereska, N., additional, Serban, A., additional, Carmen, V., additional, Cristian, S., additional, Silvia, L., additional, and Covic, A., additional

Published
2012
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47. Genome-wide association analysis identifies multiple loci related to resting heart rate

Author

Eijgelsheim, M., primary, Newton-Cheh, C., additional, Sotoodehnia, N., additional, de Bakker, P. I. W., additional, Muller, M., additional, Morrison, A. C., additional, Smith, A. V., additional, Isaacs, A., additional, Sanna, S., additional, Dorr, M., additional, Navarro, P., additional, Fuchsberger, C., additional, Nolte, I. M., additional, de Geus, E. J. C., additional, Estrada, K., additional, Hwang, S.-J., additional, Bis, J. C., additional, Ruckert, I.-M., additional, Alonso, A., additional, Launer, L. J., additional, Hottenga, J. J., additional, Rivadeneira, F., additional, Noseworthy, P. A., additional, Rice, K. M., additional, Perz, S., additional, Arking, D. E., additional, Spector, T. D., additional, Kors, J. A., additional, Aulchenko, Y. S., additional, Tarasov, K. V., additional, Homuth, G., additional, Wild, S. H., additional, Marroni, F., additional, Gieger, C., additional, Licht, C. M., additional, Prineas, R. J., additional, Hofman, A., additional, Rotter, J. I., additional, Hicks, A. A., additional, Ernst, F., additional, Najjar, S. S., additional, Wright, A. F., additional, Peters, A., additional, Fox, E. R., additional, Oostra, B. A., additional, Kroemer, H. K., additional, Couper, D., additional, Volzke, H., additional, Campbell, H., additional, Meitinger, T., additional, Uda, M., additional, Witteman, J. C. M., additional, Psaty, B. M., additional, Wichmann, H.-E., additional, Harris, T. B., additional, Kaab, S., additional, Siscovick, D. S., additional, Jamshidi, Y., additional, Uitterlinden, A. G., additional, Folsom, A. R., additional, Larson, M. G., additional, Wilson, J. F., additional, Penninx, B. W., additional, Snieder, H., additional, Pramstaller, P. P., additional, van Duijn, C. M., additional, Lakatta, E. G., additional, Felix, S. B., additional, Gudnason, V., additional, Pfeufer, A., additional, Heckbert, S. R., additional, Stricker, B. H. C., additional, Boerwinkle, E., additional, and O'Donnell, C. J., additional

Published
2010
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49. Cohort Profile: The Study of Health in Pomerania

Author

Volzke, H., primary, Alte, D., additional, Schmidt, C. O., additional, Radke, D., additional, Lorbeer, R., additional, Friedrich, N., additional, Aumann, N., additional, Lau, K., additional, Piontek, M., additional, Born, G., additional, Havemann, C., additional, Ittermann, T., additional, Schipf, S., additional, Haring, R., additional, Baumeister, S. E., additional, Wallaschofski, H., additional, Nauck, M., additional, Frick, S., additional, Arnold, A., additional, Junger, M., additional, Mayerle, J., additional, Kraft, M., additional, Lerch, M. M., additional, Dorr, M., additional, Reffelmann, T., additional, Empen, K., additional, Felix, S. B., additional, Obst, A., additional, Koch, B., additional, Glaser, S., additional, Ewert, R., additional, Fietze, I., additional, Penzel, T., additional, Doren, M., additional, Rathmann, W., additional, Haerting, J., additional, Hannemann, M., additional, Ropcke, J., additional, Schminke, U., additional, Jurgens, C., additional, Tost, F., additional, Rettig, R., additional, Kors, J. A., additional, Ungerer, S., additional, Hegenscheid, K., additional, Kuhn, J.-P., additional, Kuhn, J., additional, Hosten, N., additional, Puls, R., additional, Henke, J., additional, Gloger, O., additional, Teumer, A., additional, Homuth, G., additional, Volker, U., additional, Schwahn, C., additional, Holtfreter, B., additional, Polzer, I., additional, Kohlmann, T., additional, Grabe, H. J., additional, Rosskopf, D., additional, Kroemer, H. K., additional, Kocher, T., additional, Biffar, R., additional, John, U., additional, and Hoffmann, W., additional

Published
2010
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