1,651 results on '"Melander,O"'
Search Results
2. Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries: 23 million person-years of observation
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Kaptoge, S, Seshasai, SRK, Sun, L, Walker, M, Bolton, T, Spackman, S, Ataklte, F, Willeit, P, Bell, S, Burgess, S, Pennells, L, Altay, S, Assmann, G, Ben-Shlomo, Y, Best, LG, Björkelund, C, Blazer, DG, Brenner, H, Brunner, EJ, Dagenais, GR, Cooper, JA, Cooper, C, Crespo, CJ, Cushman, M, D'Agostino, RB, Sr, Daimon, M, Daniels, LB, Danker, R, Davidson, KW, de Jongh, RT, Donfrancesco, C, Ducimetiere, P, Elders, PJM, Engström, G, Ford, I, Gallacher, I, Bakker, SJL, Goldbourt, U, de La Cámara, G, Grimsgaard, S, Gudnason, V, Hansson, PO, Imano, H, Jukema, JW, Kabrhel, C, Kauhanen, J, Kavousi, M, Kiechl, S, Knuiman, MW, Kromhout, D, Krumholz, HM, Kuller, LH, Laatikainen, T, Lowler, DA, Meyer, HE, Mukamal, K, Nietert, PJ, Ninomiya, T, Nitsch, D, Nordestgaard, BG, Palmieri, L, Price, JF, Ridker, PM, Sun, Q, Rosengren, A, Roussel, R, Sakurai, M, Salomaa, V, Schöttker, B, Shaw, JE, Strandberg, TE, Sundström, J, Tolonen, H, Tverdal, A, Verschuren, WMM, Völzke, H, Wagenknecht, L, Wallace, RB, Wannamethee, SG, Wareham, NJ, Wassertheil-Smoller, S, Yamagishi, K, Yeap, BB, Harrison, S, Inouye, M, Griffin, S, Butterworth, AS, Wood, AM, Thompson, SG, Sattar, N, Danesh, J, Di Angelantonio, E, Tipping, RW, Russell, S, Johansen, M, Bancks, MP, Mongraw-Chaffin, M, Magliano, D, Barr, ELM, Zimmet, PZ, Whincup, PH, Willeit, J, Leitner, C, Lawlor, DA, Elwood, P, Sutherland, SE, Hunt, KJ, Selmer, RM, Haheim, LL, Ariansen, I, Tybjaer-Hansen, A, Frikkle-Schmidt, R, Langsted, A, Lo Noce, C, Balkau, B, Bonnet, F, Fumeron, F, Pablos, DL, Ferro, CR, Morales, TG, Mclachlan, S, Guralnik, J, Khaw, KT, Holleczek, B, Stocker, H, Nissinen, A, Vartiainen, E, Jousilahti, P, Harald, K, Massaro, JM, Pencina, M, Lyass, A, Susa, S, Oizumi, T, Kayama, T, Chetrit, A, Roth, J, Orenstein, L, Welin, L, Svärdsudd, K, Lissner, L, Hange, D, Mehlig, K, Tilvis, RS, Dennison, E, Westbury, L, Norman, PE, Almeida, OP, Hankey, GJ, Hata, J, Shibata, M, Furuta, Y, Bom, MT, Rutters, F, Muilwijk, M, Kraft, P, Lindstrom, S, Turman, C, Kiyama, M, Kitamura, A, Gerber, Y, Salonen, JT, van Schoor, LN, van Zutphen, EM, Melander, O, Psaty, BM, Blaha, M, de Boer, IH, Kronmal, RA, Grandits, G, Shin, H-C, Albertorio, JR, Gillum, RF, Hu, FB, Humphries, S, Hill- Briggs, F, Vrany, E, Butler, M, Schwartz, JE, Iso, H, Amouyel, P, Arveiler, D, Ferrieres, J, Gansevoort, RT, de Boer, R, Kieneker, L, Trompet, S, Kearney, P, Cantin, B, Després, JP, Lamarche, B, Laughlin, G, McEvoy, L, Aspelund, T, Thorsson, B, Sigurdsson, G, Tilly, M, Ikram, MA, Dorr, M, Schipf, S, Fretts, AM, Umans, JG, Ali, T, Shara, N, Davey-Smith, G, Can, G, Yüksel, H, Özkan, U, Nakagawa, H, Morikawa, Y, Ishizaki, M, Njølstad, I, Wilsgaard, T, Mathiesen, E, Buring, J, Cook, N, Arndt, V, Rothenbacher, D, Manson, J, Tinker, L, Shipley, M, Tabak, AG, Kivimaki, M, Packard, C, Robertson, M, Feskens, E, and Geleijnse, M
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- 2023
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3. Myocardial injury defined as elevated high-sensitivity cardiac troponin T is associated with higher mortality in patients seeking care at emergency departments with acute dyspnea
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Wessman, T, Zorlak, A, Wändell, Per, Melander, O, Carlsson, AC, and Ruge, T
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- 2023
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4. Monogenic and Polygenic Contributions to Early Onset Advanced Heart Failure Based on Whole Genome Sequencing
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Linner, E., primary, Czuba, T., additional, Gidlöf, O., additional, Lundgren, J., additional, Bollano, E., additional, Hellberg, M., additional, Celik, S., additional, Pimpalwar, N., additional, Rentzsch, P., additional, Martorella, M., additional, Gummessson, A., additional, Melander, O., additional, Albinsson, S., additional, Dellgren, G., additional, Borén, J., additional, Jeppsson, A., additional, Lumbers, T., additional, Shah, S., additional, Nilsson, J., additional, Natarajan, P., additional, Lappalainen, T., additional, Levin, M., additional, Ehrencrona, H., additional, and Smith, J., additional
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- 2024
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5. Socioeconomic and Clinical Predictors of Mortality in Patients with Acute Dyspnea
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Wessman T, Tofik R, Ruge T, and Melander O
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acute dyspnea ,emergency department ,risk factor ,immigrant ,smoking ,socioeconomic status ,mortality ,comorbidity ,metts. ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Torgny Wessman,1,2 Rafid Tofik,1,2 Thoralph Ruge,1,2 Olle Melander2,3 1Department of Emergency Medicine, Skåne University Hospital, Malmö, Sweden; 2Department of Clinical Sciences, Lund University, Malmö, Sweden; 3Department of Internal Medicine, Skåne University Hospital, Malmö, SwedenCorrespondence: Torgny WessmanDepartment of Emergency Medicine, University Hospital of Skåne, Malmö, SwedenEmail torgny.wessman@med.lu.seBackground: Factors predicting long-term prognosis in patients with acute dyspnea may guide both acute management and follow-up. The aim of this study was to identify socioeconomic and clinical risk factors for all-cause mortality among acute dyspnea patients admitted to an Emergency Department.Methods: We included 798 patients with acute dyspnea admitted to the ED of Skåne University Hospital, Malmö, Sweden from 2013 to 2016. Exposures were living in the immigrant-dense urban part of Malmö (IDUD), country of birth, annual income, comorbidities, smoking habits, medical triage priority and severity of dyspnea. Mean follow-up time was 2.2 years. Exposures were related to risk of all-cause mortality using Cox proportional hazard model.Results: During follow-up 40% died. In models adjusted for age and gender, low annual income, previous or ongoing smoking, certain comorbidities, high medical triage priority and severe dyspnea were all significantly associated with increased mortality. After adjusting for age, gender and all significant exposures, the lowest quintile of income, ongoing or previous smoking, history of serious infection, anemia, hip fracture, high medical triage priority and severe dyspnea significantly and independently predicted mortality. In contrast, neither country of birth nor living in IDUD predicted a mortality risk.Conclusion: Apart from several clinical risk factors, low annual income predicts two-year mortality risk in patients with acute dyspnea. This is not the case for country of birth and living in IDUD. Our results underline the wide range of mortality risk factors in acute dyspnea patients. Knowledge of patients’ annual income as well as certain clinical features may aid risk stratification and determining the need of follow-up both in hospital and after discharge from an ED.Keywords: acute dyspnea, emergency department, risk factor, immigrant, smoking, socioeconomic status, mortality, comorbidity, METTS
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- 2021
6. Endostatin predicts mortality in patients with acute dyspnea – A cohort study of patients seeking care in emergency departments
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Carlsson, A.C., Wessman, T., Larsson, A., Leijonberg, G., Tofik, R., Ärnlöv, J., Melander, O., and Ruge, T.
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- 2020
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7. Monogenic and Polygenic Contributions to Early Onset Advanced Heart Failure Based on Whole Genome Sequencing
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Linner, E., Czuba, T., Gidlof, O., Lundgren, J., Bollano, E., Hellberg, M., Celik, S., Pimpalwar, N., Rentzsch, Philipp, Martorella, M., Gummessson, A., Melander, O., Albinsson, S., Dellgren, G., Boren, J., Jeppsson, A., Lumbers, T., Shah, S., Nilsson, J., Natarajan, P., Lappalainen, T., Levin, M., Ehrencrona, H., Smith, J., Linner, E., Czuba, T., Gidlof, O., Lundgren, J., Bollano, E., Hellberg, M., Celik, S., Pimpalwar, N., Rentzsch, Philipp, Martorella, M., Gummessson, A., Melander, O., Albinsson, S., Dellgren, G., Boren, J., Jeppsson, A., Lumbers, T., Shah, S., Nilsson, J., Natarajan, P., Lappalainen, T., Levin, M., Ehrencrona, H., and Smith, J.
- Abstract
QC 20240828
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- 2024
8. TNFR1 is associated with short-term mortality in patients with diabetes and acute dyspnea seeking care at the emergency department
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Wändell, P., Carlsson, A. C., Larsson, A., Melander, O., Wessman, T., Ärnlöv, J., and Ruge, T.
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- 2020
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9. Impact of a short-term Mediterranean diet intervention on plasma metabolites: a pilot study.
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Smith, E., Ottosson, F., Ericson, U., Hellstrand, S., Rizzo, M., Sukruang, K., Pizza, V., Orho-Melander, M., Nilsson, P. M., Kennbäck, C., Fernandez, C., Antonini, P., Di Somma, S., and Melander, O.
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DIETARY patterns ,MEDITERRANEAN diet ,TYPE 2 diabetes ,CORONARY artery disease ,HEART metabolism disorders - Abstract
Background: Dietary habits significantly influence the risks of type 2 diabetes and cardiovascular disease. Through metabolomics, we've previously measured plasma metabolites to gauge dietary quality, introducing a healthy dietary metabolic signature (HDMS) linked to a decreased risk of future type 2 diabetes and coronary artery disease. Objectives: To assess the impact of a 6-day dietary intervention on plasma metabolites and the HDMS. Methods: Fifty-nine Swedish participants (71% women, mean age 69 years) underwent a 6-day Mediterranean diet (MD) intervention in Italy's Cilento region. All meals, crafted from local recipes and ingredients, were provided. Metabolite profiling pre- and post-intervention was conducted with a UHPLC-QTOF. Alterations in metabolite levels and the HDMS were examined using paired T-test. Results: The MD intervention notably enhanced the HDMS across participants (mean increase: 1.3 standard deviations (SD), 95% CI 1.1–1.4, p = 6E-25). Out of 109 metabolites, 66 exhibited significant alterations (fdr adjusted p < 0.05). Among the 10 most significant changes, increases were observed in several diet related metabolites such as pipecolate, hippurate, caffeine, homostachydrine, acylcarnitine C11:0, acetylornithine, beta-carotene and 7-methylguanine. The most significant decreases manifested in piperine and 3-methylhistidine. Conclusions: The HDMS, which is linked to a healthy diet and inversely associated with cardiometabolic disease, was significantly improved by the 6-day Mediterranean diet intervention. Notably, metabolite markers previously shown to be indicative of the intake of vegetables, fruits, grains, and legumes increased, while markers previously associated with red meat consumption decreased. These findings highlight the potential of short-term dietary interventions to induce significant changes in plasma metabolite profiles. [ABSTRACT FROM AUTHOR]
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- 2024
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10. ST2 Predicts Mortality In Patients With Acute Hypercapnic Respiratory Failure Treated With Noninvasive Positive Pressure Ventilation
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Jónsdóttir B, Ziebell Severinsen M, von Wowern F, San Miguel C, Goetze JP, and Melander O
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Acute Hypercapnic Respiratory Failure ,Noninvasive Positive Pressure Ventilation ,Chronic Obstructive Pulmonary Disease ,Heart Failure ,Obesity Hypoventilation Syndrome ,Predictive Biomarkers ,Diseases of the respiratory system ,RC705-779 - Abstract
Brynja Jónsdóttir,1–3 Marie Ziebell Severinsen,4 Fredrik von Wowern,1,3 Carmen San Miguel,3 Jens P Goetze,4 Olle Melander1,3 1Department of Clinical Sciences Malmo, Faculty of Medicine, Lund University, Lund, Sweden; 2Department of Pulmonary Medicine and Allergology, Skåne University Hospital, Malmö, Sweden; 3Department of Internal Medicine and Emergency Medicine, Skåne University Hospital, Malmö, Sweden; 4Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, DenmarkCorrespondence: Brynja JónsdóttirDepartment of Pulmonary Medicine and Allergology, Skånes Universitetssjukhus Malmö, Södra Förstadsgatan, Malmö 20502, SwedenEmail brynjajo@gmail.comBackground: Patients with Acute Hypercapnic Respiratory Failure (AHRF) are often treated with Noninvasive Positive Pressure Ventilation (NPPV). In this heterogeneous patient group, there is a lack of clinical tools for predicting mortality and outcome.Aims: In order to facilitate the choice of treatment in patients with AHRF we evaluated the protein ST2, an established biomarker for cardiac stress, and its role in predicting mortality in patients with AHRF treated with NPPV. We also examined if ST2 baseline levels and changes during the first 12 hrs of treatment were predictive of treatment outcome.Methods: The study population consisted of 46 patients treated with NPPV for AHRF. Background data and clinical parameters were obtained and blood samples taken at various time points during the treatment. During the follow-up period of 18 months, the prognostic value of ST2 with regards to mortality was evaluated using Cox proportional hazard model.Results: Of the 46 patients, there were 3 subgroups in regards to primary diagnosis: Acute Exacerbation of COPD (n=34), Acute Heart Failure (n=8) and Acute Exacerbation in Obesity Hypoventilation Syndrome (n=4). We found that ST2 was an independent predictor of both short-term and long-term mortality during the follow-up period. The Hazard Ratio (HR) per 1-SD increment of ST2 for 28-day mortality was 11.00 (95% CI 1.8–67.2, p 0.009) and for 18-month mortality 2.11 (95% CI 1.4–3.2, p 0.001). The results seem to be driven by the largest subgroup of patients, with Acute Exacerbation of COPD, and deaths within the first 28 days. Furthermore, changes in ST2 values during the first 12 hrs of treatment were not predictive of treatment outcome.Conclusion: Our results show that ST2 is a target to explore further as a predictor of short-term mortality in patients with AHRF treated with NPPV.Keywords: acute hypercapnic respiratory failure, noninvasive positive pressure ventilation, chronic obstructive pulmonary disease, heart failure
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- 2019
11. Genome‐wide analysis of genetic determinants of circulating factor VII‐activating protease (FSAP) activity
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Olsson, M., Stanne, T.M., Pedersen, A., Lorentzen, E., Kara, E., Martinez‐Palacian, A., Rønnow Sand, N.P., Jacobsen, A.F., Sandset, P.M., Sidelmann, J.J., Engström, G., Melander, O., Kanse, S.M., and Jern, C.
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- 2018
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12. A genetic risk score for hypertension is associated with risk of thoracic aortic aneurysm
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Tagetti, A., Bonafini, S., Ohlsson, T., Engström, G., Almgren, P., Minuz, P., Smith, G., Melander, O., and Fava, C.
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- 2019
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13. Increased mortality among acute respiratory distress patients from immigrant dense urban districts
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Wessman T, Tofik R, Gränsbo K, and Melander O
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Dyspnea ,Emergency department ,Mortality ,Socioeconomic ,Income ,ADAPT. ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Torgny Wessman,1,2 Rafid Tofik,1,2 Klas Gränsbo,2,3 Olle Melander2,3 1Department of Emergency Medicine, Skåne University Hospital, Malmö, Sweden; 2Department of Clinical Sciences, Lund University, Malmö, Sweden; 3Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden Purpose: This study investigated whether living in immigrant dense urban districts (IDUDs) and low-income areas in the city of Malmö predicted 5-year mortality among patients admitted to the emergency department (ED) because of acute respiratory distress. Patients and methods: We randomly selected 184 patients with acute respiratory distress during 2007, visiting the ED at Skåne University Hospital, Malmö. In 2007, Malmö had 36% first- and second-generation immigrants. The main exposure was defined as being resident in any of the five IDUDs of Malmö compared to being resident in the five districts of Malmö with the highest proportion of Sweden-born inhabitants (SDUDs). We recorded vital parameters; medical triage priority according to Adaptive Process Triage (ADAPT), ICD-10 diagnoses, and the mean annual income for the patient’s urban district. We examined 5-year mortality risk using Cox proportional hazards model. Results: After adjustment for age and gender, patients from IDUDs (n=100, 54%) had an HR (95% CI) of 1.65 (1.087–2.494; P=0.019) regarding mortality at 5-year follow-up. Patients in the lowest vs highest income quartile had an HR of 2.00 (1.06–3.79; P=0.032) regarding mortality at 5-year follow-up. Age, male gender, presence of cardiopulmonary disease, and ADAPT priority also independently predicted the 5-year mortality. The excess risk of 5-year mortality associated with living in IDUDs remained significant after adjustment for age, gender, ADAPT priority, presence of cardiopulmonary disease, and income with an HR of 1.79 (1.15–2.78; P=0.010). Conclusion: Living in an IDUD is a strong independent risk factor for 5-year mortality in patients with acute respiratory distress. The cause is unknown. Our study suggests a need for better structured follow-up of cardiopulmonary disease in such patients. Keywords: dyspnea, emergency department, mortality, socioeconomic, income, ADAPT
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- 2019
14. High circulating levels of midregional proenkephalin A predict vascular dementia: a population-based prospective study
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Holm, H., Nägga, K., Nilsson, E. D., Ricci, F., Melander, O., Hansson, O., Bachus, E., Fedorowski, A., and Magnusson, M.
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- 2020
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15. Association between systemic leptin and neurotensin concentration in adult individuals with and without type 2 diabetes mellitus
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Barchetta, I., Ciccarelli, G., Cimini, F. A., Ceccarelli, V., Orho-Melander, M., Melander, O., and Cavallo, M. G.
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- 2018
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16. The association between plasma proneurotensin and glucose regulation is modified by country of birth
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Fawad, A., Nilsson, P. M., Struck, J., Bergmann, A., Melander, O., and Bennet, L.
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- 2019
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17. Genetic insights into resting heart rate and its role in cardiovascular disease.
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Vegte, Y.J. van de, Eppinga, R.N., Ende, M.Y. van der, Hagemeijer, Y.P., Mahendran, Y., Salfati, E., Smith, A.V., Tan, V.Y., Arking, D.E., Ntalla, I., Appel, E.V., Schurmann, C., Brody, J.A., Rueedi, R., Polasek, O., Sveinbjornsson, G., Lecoeur, C., Ladenvall, C., Zhao, J.H., Isaacs, A., Wang, L., Luan, Jian'an, Hwang, S.J., Mononen, N., Auro, K., Jackson, A.U., Bielak, L.F., Zeng, L., Shah, N., Nethander, M., Campbell, A., Rankinen, T., Pechlivanis, S., Qi, L., Zhao, Wei, Rizzi, F., Tanaka, T., Robino, A., Cocca, M., Lange, L., Müller-Nurasyid, M., Roselli, C., Zhang, W, Kleber, M.E., Guo, X., Lin, H.J., Pavani, F., Galesloot, T.E., Noordam, R., Milaneschi, Y., Schraut, K.E., Hoed, M. den, Degenhardt, F., Trompet, S., Berg, M.E. van den, Pistis, G., Tham, Y.C., Weiss, S., Sim, X.S., Li, H.L., Most, P.J. van der, Nolte, I.M., Lyytikäinen, L.P., Said, M.A., Witte, D.R., Iribarren, C., Launer, L., Ring, S.M., Vries, P.S. de, Sever, P., Linneberg, A., Bottinger, E.P., Padmanabhan, S., Psaty, B.M., Sotoodehnia, N., Kolcic, I., Arnar, D.O., Gudbjartsson, D.F., Holm, H., Balkau, B., Silva, C.T., Newton-Cheh, C.H., Nikus, K., Salo, P., Mohlke, K.L., Peyser, P.A., Schunkert, H., Lorentzon, M., Lahti, J., Rao, D.C., Cornelis, M.C., Faul, J.D., Smith, J.A., Stolarz-Skrzypek, K., Bandinelli, S., Concas, M.P., Sinagra, G., Meitinger, T., Waldenberger, M., Sinner, M.F., Strauch, K., Delgado, G.E., Taylor, K.D., Yao, J., Foco, L., Melander, O., Graaf, J. de, Mutsert, R. de, Geus, E.J.C. de, Johansson, Å., Joshi, P.K., Lind, L., Franke, A., Macfarlane, P.W., Tarasov, K.V., Tan, N., Felix, S.B., Tai, E.S., Quek, D.Q., Snieder, H., Ormel, J., Ingelsson, M., Lindgren, C., Morris, A.P., Raitakari, O.T., Hansen, T., Assimes, T., Gudnason, V., Timpson, N.J., Morrison, A.C., Munroe, P.B., Strachan, D.P., Grarup, N., Loos, R.J.F., Heckbert, S.R., Vollenweider, P., Hayward, C., Stefansson, K., Froguel, P., Groop, L., Wareham, N.J., Duijn, C.M. van, Feitosa, M.F., O'Donnell, C.J., Kähönen, M., Perola, M., Boehnke, M., Kardia, S.L.R., Erdmann, J., Palmer, C.N.A., Ohlsson, C., Porteous, D.J., Eriksson, J.G., Bouchard, C., Moebus, S., Kraft, P., Weir, D.R., Cusi, D., Ferrucci, L., Ulivi, S., Girotto, G., Correa, A., Kääb, S., Peters, A., Chambers, J.C., Kooner, J.S., März, W., Rotter, J.I., Hicks, A.A., Smith, J.G., Kiemeney, L.A.L.M., Mook-Kanamori, D.O., Penninx, B.W.J.H., Gyllensten, U., Wilson, J.F., Burgess, S., Sundström, J., Lieb, W., Jukema, J.W., Eijgelsheim, M., Lakatta, E.L.M., Cheng, C.Y., Dörr, M., Wong, T.Y., Sabanayagam, C., Oldehinkel, A.J., Riese, H., Lehtimäki, T., Verweij, N., Harst, P. van der, Vegte, Y.J. van de, Eppinga, R.N., Ende, M.Y. van der, Hagemeijer, Y.P., Mahendran, Y., Salfati, E., Smith, A.V., Tan, V.Y., Arking, D.E., Ntalla, I., Appel, E.V., Schurmann, C., Brody, J.A., Rueedi, R., Polasek, O., Sveinbjornsson, G., Lecoeur, C., Ladenvall, C., Zhao, J.H., Isaacs, A., Wang, L., Luan, Jian'an, Hwang, S.J., Mononen, N., Auro, K., Jackson, A.U., Bielak, L.F., Zeng, L., Shah, N., Nethander, M., Campbell, A., Rankinen, T., Pechlivanis, S., Qi, L., Zhao, Wei, Rizzi, F., Tanaka, T., Robino, A., Cocca, M., Lange, L., Müller-Nurasyid, M., Roselli, C., Zhang, W, Kleber, M.E., Guo, X., Lin, H.J., Pavani, F., Galesloot, T.E., Noordam, R., Milaneschi, Y., Schraut, K.E., Hoed, M. den, Degenhardt, F., Trompet, S., Berg, M.E. van den, Pistis, G., Tham, Y.C., Weiss, S., Sim, X.S., Li, H.L., Most, P.J. van der, Nolte, I.M., Lyytikäinen, L.P., Said, M.A., Witte, D.R., Iribarren, C., Launer, L., Ring, S.M., Vries, P.S. de, Sever, P., Linneberg, A., Bottinger, E.P., Padmanabhan, S., Psaty, B.M., Sotoodehnia, N., Kolcic, I., Arnar, D.O., Gudbjartsson, D.F., Holm, H., Balkau, B., Silva, C.T., Newton-Cheh, C.H., Nikus, K., Salo, P., Mohlke, K.L., Peyser, P.A., Schunkert, H., Lorentzon, M., Lahti, J., Rao, D.C., Cornelis, M.C., Faul, J.D., Smith, J.A., Stolarz-Skrzypek, K., Bandinelli, S., Concas, M.P., Sinagra, G., Meitinger, T., Waldenberger, M., Sinner, M.F., Strauch, K., Delgado, G.E., Taylor, K.D., Yao, J., Foco, L., Melander, O., Graaf, J. de, Mutsert, R. de, Geus, E.J.C. de, Johansson, Å., Joshi, P.K., Lind, L., Franke, A., Macfarlane, P.W., Tarasov, K.V., Tan, N., Felix, S.B., Tai, E.S., Quek, D.Q., Snieder, H., Ormel, J., Ingelsson, M., Lindgren, C., Morris, A.P., Raitakari, O.T., Hansen, T., Assimes, T., Gudnason, V., Timpson, N.J., Morrison, A.C., Munroe, P.B., Strachan, D.P., Grarup, N., Loos, R.J.F., Heckbert, S.R., Vollenweider, P., Hayward, C., Stefansson, K., Froguel, P., Groop, L., Wareham, N.J., Duijn, C.M. van, Feitosa, M.F., O'Donnell, C.J., Kähönen, M., Perola, M., Boehnke, M., Kardia, S.L.R., Erdmann, J., Palmer, C.N.A., Ohlsson, C., Porteous, D.J., Eriksson, J.G., Bouchard, C., Moebus, S., Kraft, P., Weir, D.R., Cusi, D., Ferrucci, L., Ulivi, S., Girotto, G., Correa, A., Kääb, S., Peters, A., Chambers, J.C., Kooner, J.S., März, W., Rotter, J.I., Hicks, A.A., Smith, J.G., Kiemeney, L.A.L.M., Mook-Kanamori, D.O., Penninx, B.W.J.H., Gyllensten, U., Wilson, J.F., Burgess, S., Sundström, J., Lieb, W., Jukema, J.W., Eijgelsheim, M., Lakatta, E.L.M., Cheng, C.Y., Dörr, M., Wong, T.Y., Sabanayagam, C., Oldehinkel, A.J., Riese, H., Lehtimäki, T., Verweij, N., and Harst, P. van der
- Abstract
Contains fulltext : 296013.pdf (Publisher’s version ) (Open Access), Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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- 2023
18. Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality
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Magnussen, C, Ojeda, F, Leong, D, Alegre-Diaz, J, Amouyel, P, Aviles-Santa, L, De Bacquer, D, Ballantyne, C, Bernabé-Ortiz, A, Bobak, M, Brenner, H, Carrillo-Larco, R, de Lemos, J, Dobson, A, Dörr, M, Donfrancesco, C, Drygas, W, Dullaart, R, Engström, G, Ferrario, M, Ferrières, J, de Gaetano, G, Goldbourt, U, Gonzalez, C, Grassi, G, Hodge, A, Hveem, K, Iacoviello, L, Ikram, M, Irazola, V, Jobe, M, Jousilahti, P, Kaleebu, P, Kavousi, M, Kee, F, Khalili, D, Koenig, W, Kontsevaya, A, Kuulasmaa, K, Lackner, K, Leistner, D, Lind, L, Linneberg, A, Lorenz, T, Lyngbakken, M, Malekzadeh, R, Malyutina, S, Mathiesen, E, Melander, O, Metspalu, A, Miranda, J, Moitry, M, Mugisha, J, Nalini, M, Nambi, V, Ninomiya, T, Oppermann, K, D'Orsi, E, Pająk, A, Palmieri, L, Panagiotakos, D, Perianayagam, A, Peters, A, Poustchi, H, Prentice, A, Prescott, E, Risérus, U, Salomaa, V, Sans, S, Sakata, S, Schöttker, B, Schutte, A, Sepanlou, S, Sharma, S, Shaw, J, Simons, L, Söderberg, S, Tamosiunas, A, Thorand, B, Tunstall-Pedoe, H, Twerenbold, R, Vanuzzo, D, Veronesi, G, Waibel, J, Wannamethee, S, Watanabe, M, Wild, P, Yao, Y, Zeng, Y, Ziegler, A, Blankenberg, S, Magnussen, Christina, Ojeda, Francisco M, Leong, Darryl P, Alegre-Diaz, Jesus, Amouyel, Philippe, Aviles-Santa, Larissa, De Bacquer, Dirk, Ballantyne, Christie M, Bernabé-Ortiz, Antonio, Bobak, Martin, Brenner, Hermann, Carrillo-Larco, Rodrigo M, de Lemos, James, Dobson, Annette, Dörr, Marcus, Donfrancesco, Chiara, Drygas, Wojciech, Dullaart, Robin P, Engström, Gunnar, Ferrario, Marco M, Ferrières, Jean, de Gaetano, Giovanni, Goldbourt, Uri, Gonzalez, Clicerio, Grassi, Guido, Hodge, Allison M, Hveem, Kristian, Iacoviello, Licia, Ikram, M Kamran, Irazola, Vilma, Jobe, Modou, Jousilahti, Pekka, Kaleebu, Pontiano, Kavousi, Maryam, Kee, Frank, Khalili, Davood, Koenig, Wolfgang, Kontsevaya, Anna, Kuulasmaa, Kari, Lackner, Karl J, Leistner, David M, Lind, Lars, Linneberg, Allan, Lorenz, Thiess, Lyngbakken, Magnus Nakrem, Malekzadeh, Reza, Malyutina, Sofia, Mathiesen, Ellisiv B, Melander, Olle, Metspalu, Andres, Miranda, J Jaime, Moitry, Marie, Mugisha, Joseph, Nalini, Mahdi, Nambi, Vijay, Ninomiya, Toshiharu, Oppermann, Karen, d'Orsi, Eleonora, Pająk, Andrzej, Palmieri, Luigi, Panagiotakos, Demosthenes, Perianayagam, Arokiasamy, Peters, Annette, Poustchi, Hossein, Prentice, Andrew M, Prescott, Eva, Risérus, Ulf, Salomaa, Veikko, Sans, Susana, Sakata, Satoko, Schöttker, Ben, Schutte, Aletta E, Sepanlou, Sadaf G, Sharma, Sanjib Kumar, Shaw, Jonathan E, Simons, Leon A, Söderberg, Stefan, Tamosiunas, Abdonas, Thorand, Barbara, Tunstall-Pedoe, Hugh, Twerenbold, Raphael, Vanuzzo, Diego, Veronesi, Giovanni, Waibel, Julia, Wannamethee, S Goya, Watanabe, Masafumi, Wild, Philipp S, Yao, Yao, Zeng, Yi, Ziegler, Andreas, Blankenberg, Stefan, Magnussen, C, Ojeda, F, Leong, D, Alegre-Diaz, J, Amouyel, P, Aviles-Santa, L, De Bacquer, D, Ballantyne, C, Bernabé-Ortiz, A, Bobak, M, Brenner, H, Carrillo-Larco, R, de Lemos, J, Dobson, A, Dörr, M, Donfrancesco, C, Drygas, W, Dullaart, R, Engström, G, Ferrario, M, Ferrières, J, de Gaetano, G, Goldbourt, U, Gonzalez, C, Grassi, G, Hodge, A, Hveem, K, Iacoviello, L, Ikram, M, Irazola, V, Jobe, M, Jousilahti, P, Kaleebu, P, Kavousi, M, Kee, F, Khalili, D, Koenig, W, Kontsevaya, A, Kuulasmaa, K, Lackner, K, Leistner, D, Lind, L, Linneberg, A, Lorenz, T, Lyngbakken, M, Malekzadeh, R, Malyutina, S, Mathiesen, E, Melander, O, Metspalu, A, Miranda, J, Moitry, M, Mugisha, J, Nalini, M, Nambi, V, Ninomiya, T, Oppermann, K, D'Orsi, E, Pająk, A, Palmieri, L, Panagiotakos, D, Perianayagam, A, Peters, A, Poustchi, H, Prentice, A, Prescott, E, Risérus, U, Salomaa, V, Sans, S, Sakata, S, Schöttker, B, Schutte, A, Sepanlou, S, Sharma, S, Shaw, J, Simons, L, Söderberg, S, Tamosiunas, A, Thorand, B, Tunstall-Pedoe, H, Twerenbold, R, Vanuzzo, D, Veronesi, G, Waibel, J, Wannamethee, S, Watanabe, M, Wild, P, Yao, Y, Zeng, Y, Ziegler, A, Blankenberg, S, Magnussen, Christina, Ojeda, Francisco M, Leong, Darryl P, Alegre-Diaz, Jesus, Amouyel, Philippe, Aviles-Santa, Larissa, De Bacquer, Dirk, Ballantyne, Christie M, Bernabé-Ortiz, Antonio, Bobak, Martin, Brenner, Hermann, Carrillo-Larco, Rodrigo M, de Lemos, James, Dobson, Annette, Dörr, Marcus, Donfrancesco, Chiara, Drygas, Wojciech, Dullaart, Robin P, Engström, Gunnar, Ferrario, Marco M, Ferrières, Jean, de Gaetano, Giovanni, Goldbourt, Uri, Gonzalez, Clicerio, Grassi, Guido, Hodge, Allison M, Hveem, Kristian, Iacoviello, Licia, Ikram, M Kamran, Irazola, Vilma, Jobe, Modou, Jousilahti, Pekka, Kaleebu, Pontiano, Kavousi, Maryam, Kee, Frank, Khalili, Davood, Koenig, Wolfgang, Kontsevaya, Anna, Kuulasmaa, Kari, Lackner, Karl J, Leistner, David M, Lind, Lars, Linneberg, Allan, Lorenz, Thiess, Lyngbakken, Magnus Nakrem, Malekzadeh, Reza, Malyutina, Sofia, Mathiesen, Ellisiv B, Melander, Olle, Metspalu, Andres, Miranda, J Jaime, Moitry, Marie, Mugisha, Joseph, Nalini, Mahdi, Nambi, Vijay, Ninomiya, Toshiharu, Oppermann, Karen, d'Orsi, Eleonora, Pająk, Andrzej, Palmieri, Luigi, Panagiotakos, Demosthenes, Perianayagam, Arokiasamy, Peters, Annette, Poustchi, Hossein, Prentice, Andrew M, Prescott, Eva, Risérus, Ulf, Salomaa, Veikko, Sans, Susana, Sakata, Satoko, Schöttker, Ben, Schutte, Aletta E, Sepanlou, Sadaf G, Sharma, Sanjib Kumar, Shaw, Jonathan E, Simons, Leon A, Söderberg, Stefan, Tamosiunas, Abdonas, Thorand, Barbara, Tunstall-Pedoe, Hugh, Twerenbold, Raphael, Vanuzzo, Diego, Veronesi, Giovanni, Waibel, Julia, Wannamethee, S Goya, Watanabe, Masafumi, Wild, Philipp S, Yao, Yao, Zeng, Yi, Ziegler, Andreas, and Blankenberg, Stefan
- Abstract
BACKGROUND: Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking. METHODS: We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality. RESULTS: Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6). CONCLUSIONS: Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the
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- 2023
19. Association between copeptin and declining glomerular filtration rate in people with newly diagnosed diabetes. The Skaraborg Diabetes Register
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Pikkemaat, M., Melander, O., and Bengtsson Boström, K.
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- 2015
- Full Text
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20. Risk factors for the progression of carotid intima-media thickness over a 16-year follow-up period: The Malmö Diet and Cancer Study
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Rosvall, M., Persson, M., Östling, G., Nilsson, P.M., Melander, O., Hedblad, B., and Engström, G.
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- 2015
- Full Text
- View/download PDF
21. Additional file 1 of Myocardial injury defined as elevated high-sensitivity cardiac troponin T is associated with higher mortality in patients seeking care at emergency departments with acute dyspnea
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Wessman, T, Zorlak, A, Wändell, Per, Melander, O, Carlsson, AC, and Ruge, T
- Abstract
Supplementary Material 1
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- 2023
- Full Text
- View/download PDF
22. ESICM LIVES 2016: part two: Milan, Italy. 1–5 October 2016
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Sivakumar, S., Taccone, F. S., Desai, K. A., Lazaridis, C., Skarzynski, M., Sekhon, M., Henderson, W., Griesdale, D., Chapple, L., Deane, A., Williams, L., Strickland, R., Lange, K., Heyland, D., Chapman, M., Rowland, M. J., Garry, P., Westbrook, J., Corkill, R., Antoniades, C. A., Pattinson, K. T., Fatania, G., Strong, A. J., Myers, R. B., Lazaridis, C., Jermaine, C. M., Robertson, C. S., Rusin, C. G., Hofmeijer, J., Sondag, L., Tjepkema-Cloostermans, M. C., Beishuizen, A., Bosch, F. H., van Putten, M. J. A. M., Carteron, L., Patet, C., Solari, D., Oddo, M., Ali, M. A., Dias, C., Almeida, R., Vaz-Ferreira, A., Silva, J., Monteiro, E., Cerejo, A., Rocha, A. P., Elsayed, A. A., Abougabal, A. M., Beshey, B. N., Alzahaby, K. M., Pozzebon, S., Ortiz, A. Blandino, Cristallini, S., Lheureux, O., Brasseur, A., Vincent, J. L., Creteur, J., Taccone, F. S., Hravnak, M., Yousef, K., Chang, Y., Crago, E., Friedlander, R. M., Abdelmonem, S. A., Tahon, S. A., Helmy, T. A., Meligy, H. S., Puig, F., Dunn-Siegrist, I., Pugin, J., Gupta, S., Govil, D., Srinivasan, S., Patel, S. J., N, J. K., Gupta, A., Tomar, D. S., Shafi, M., Harne, R., Arora, D. P., Talwar, N., Mazumdar, S., Papakrivou, E. E., Makris, D., Manoulakas, E., Tsolaki, B., Karadodas, B., Zakynthinos, E., Garcia, I. Palacios, Martin, A. Diaz, Encinares, V. Sanchez, Ibañez, M. Pachón, Montero, J. Garnacho, Labrador, G., Cangueiro, T. Cebrero, Poulose, V., Koh, J., Kam, J. W., Yeter, H., Kara, A., Aktepe, O., Topeli, A., Tsolakoglou, I., Intas, G., Stergiannis, P., Kolaros, A. A., Chalari, E., Athanasiadou, E., Martika, A., Fildisis, G., Faivre, V., Mengelle, C., Favier, B., Payen, D., Poppe, A., Winkler, M. S., Mudersbach, E., Schreiber, J., Wruck, M. L., Schwedhelm, E., Kluge, S., Zöllner, C., Tavladaki, T., Spanaki, A. M., Dimitriou, H., Kondili, E., Choulaki, C., Meleti, E., Kafetzopoulos, D., Georgopoulos, D., Briassoulis, G., la Torre, A. García-de, de la Torre-Prados, M. V., Tsvetanova-Spasova, T., Nuevo-Ortega, P., Rueda-Molina, C., Fernández-Porcel, A., Camara-Sola, E., Salido-Díaz, L., García-Alcántara, A., Tavladaki, T., Spanaki, A. M., Dimitriou, H., Kondili, E., Choulaki, C., Meleti, D. E., Kafetzopoulos, D., Georgopoulos, D., Briassoulis, G., Suberviola, B., Riera, J., Rellan, L., Sanchez, M., Robles, J. C., Lopez, E., Vicente, R., Miñambres, E., Santibañez, M., Le Guen, M., Moore, J., Mason, N., Windpassinger, M., Plattner, O., Mascha, E., Sessler, D. I., Research, Outcomes, Melia, U., Fontanet, J., van den Berg, J. P., Struys, M. M. R. F., Vereecke, H. E. M., Jensen, E. W., Rood, P. J. T., van de Schoor, F., van Tertholen, K., Pickkers, P., van den Boogaard, M., Beardow, Z. J., Redhead, H., Paramasivam, K., Numan, T., van den Boogaard, M., Kamper, A. M., Rood, P., Peelen, L. M., Zeman, P. M., Slooter, A. J., van Ewijk, C. E., Jacobs, G. E., Girbes, A. R. J., Myatra, S. N., Harish, M. M., Prabu, N. R., Siddiqui, S., Kulkarni, A. P., Divatia, J. V., Murbach, L. D., Leite, M. A., Osaku, E. F., Costa, C. R. L. M., Pelenz, M., Neitzke, N. M., Moraes, M. M., Jaskowiak, J. L., Silva, M. M. M., Zaponi, R. S., Abentroth, L. R. L., Ogasawara, S. M., Jorge, A. C., Duarte, P. A. D., Hernández-Sánchez, N., Sánchez-Hurtado, L. A., García-Guillen, F. J., Ñamendys-Silva, S. A., Maghsoudi, B., Emami, M., Khosravi, M. B., Zand, F., Tabatabaie, H. R., Masjedi, M., Sabetiyan, G., Mokri, A., Troubleyn, J., Diltoer, M., Jacobs, R., Nguyen, D. N., De Waele, E., De Regt, J., Honoré, P. M., Van Gorp, V., Spapen, H. D., Contreras, R. S., Toapanta, N. D., Moreno, G., Sabater, J., Torrado, H., Gonzalez, M., Marin, M., Farigola, E., Gonzalez, A., Fernandez, J., Vera, A., Gisbert, X., Juliá, C., Uya, J., Corral, L., Elias-Jones, I., Gemmell, L., MacKay, A., Randall, D., Adwaney, A., Blunden, M., Prowle, J. R., Kirwan, C. J., Thomas, N., Martin, A., Owen, H., Darwin, L., Conway, D., Atkinson, D., Sharman, M., Moore, J., Barbanti, C., Amour, J., Gaudard, P., Rozec, B., Mauriat, P., M’rini, M., Leger, P. L., Cambonie, G., Liet, J. M., Girard, C., Laroche, S., Damas, P., Assaf, Z., Loron, G., Lecourt, L., Pouard, P., Randall, D., Adwaney, A., Blunden, M., Prowle, J.R., Kirwan, C. J., Kim, S. H., Na, S., Kim, J., Oh, S. Y., Jung, C. W., Yoo, S. H., Min, S. H., Chung, E. J., Lee, H., Lee, N. J., Lee, K. W., Suh, K. S., Ryu, H. G., Marshall, D. C., Goodson, R. J., Salciccioli, J. D., Shalhoub, J., Potter, E. K., Kirk-Bayley, J., Karanjia, N. D., Forni, L. G., Creagh-Brown, B. C., Bossy, M., Nyman, M., Tailor, A., Creagh-Brown, B., D’Antini, D., Spadaro, S., Valentino, F., Sollitto, F., Cinnella, G., Mirabella, L., Calvo, F. J. Redondo, Bejarano, N., Padilla, D., Baladron, V., Villajero, P., Villazala, R., Redondo, J., Yuste, A. S., Liu, J., Shen, F., Teboul, J. L., Anguel, N., Beurton, A., Bezaz, N., Richard, C., Monnet, X., Fossali, T., Colombo, R., Ottolina, D., Rossetti, M., Mazzucco, C., Marchi, A., Porta, A., Catena, E., Tollisen, K. H., Andersen, G. Ø., Heyerdahl, F., Jacobsen, D., de Waard, M. C., Girbes, A. R. J., van IJzendoorn, M. C. O., Buter, H., Kingma, W. P., Navis, G. J., Boerma, E. C., Rulisek, J., Balik, M., Zacharov, S., Kim, H. S., Jeon, S. J., Namgung, H., Lee, E., Lee, E., Cho, Y. J., Lee, Y. J., Huang, A., Cioccari, L., Luethi, N., Mårtensson, J., Bellomo, R., Forsberg, M., Edman, G., Höjer, J., Forsberg, S., Freile, M. T. Chiquito, Hidalgo, F. N., Molina, J. A. Martinez, Lecumberri, R., Rosselló, A. Figuerola, Travieso, P. Medrano, Leon, G. Tuero, Sanchez, J. Gonzalez, Frias, L. Sahuquillo, Rosello, D. Balsells, Verdejo, J. A. Garcia, Serrano, J. A. Noria, Winterwerp, D., van Galen, T., Vazin, A., Karimzade, I., Zand, A., Ozen, E., Ekemen, S., Akcan, A., Sen, E., Yelken, B. Buyukkidan, Kureshi, N., Fenerty, L., Thibault-Halman, G., Erdogan, M., Walling, S., Green, R. S., Clarke, D. B., Briassoulis, P., Kalimeris, K., Ntzouvani, A., Nomikos, T., Papaparaskeva, K., Politi, E., Kostopanagiotou, G., Crewdson, K., Rehn, M., Weaver, A., Brohi, K., Lockey, D., Wright, S., Thomas, K., Baker, C., Mansfield, L., Stafford, V., Wade, C., Watson, G., Bryant, A., Chadwick, T., Shen, J., Wilkinson, J., Furneval, J., Henderson, A., Hugill, K., Howard, P., Roy, A., Bonner, S., Baudouin, S., Ramírez, C. Sánchez, Escalada, S. Hípola, Viera, M. A. Hernández, Santana, M. Cabrera, Balcázar, L. Caipe, Monroy, N. Sangil, Campelo, F. Artiles, Vázquez, C. F. Lübbe, Santana, P. Saavedra, Santana, S. Ruiz, Carteron, L., Patet, C., Quintard, H., Solari, D., Bouzat, P., Oddo, M., Wollersheim, T., Malleike, J., Haas, K., Carbon, N., Schneider, J., Birchmeier, C., Fielitz, J., Spuler, S., Weber-Carstens, S., Enseñat, L., Pérez-Madrigal, A., Saludes, P., Proença, L., Gruartmoner, G., Espinal, C., Mesquida, J., Huber, W., Eckmann, M., Elkmann, F., Gruber, A., Lahmer, T., Mayr, U., Herner, A., Schellnegger, R., Schneider, J., Schmid, R. M., Ayoub, W., Samy, W., Esmat, A., Battah, A., Mukhtar, S., Mongkolpun, W., Cortés, D. Orbegozo, Cordeiro, C. P. R., Vincent, J. L., Creteur, J., Funcke, S., Groesdonk, H., Saugel, B., Wagenpfeil, G., Wagenpfeil, S., Reuter, D. A., Fernandez, M. M., Fernandez, R., Magret, M., González-Castro, A., Bouza, M. T., Ibañez, M., García, C., Balerdi, B., Mas, A., Arauzo, V., Añón, J. M., Ruiz, F., Ferreres, J., Tomás, R., Alabert, M., Tizón, A. I., Altaba, S., Llamas, N., Goligher, E C., Fan, E., Herridge, M., Vorona, S., Sklar, M., Dres, M., Rittayamai, N., Lanys, A., Urrea, C., Tomlinson, G., Reid, W. D., Rubenfeld, G. D., Kavanagh, B. P., Brochard, L. J., Ferguson, N. D., Neto, A. Serpa, de Abreu, M. Gama, Pelosi, P., Schultz, M. J., Guérin, C., Papazian, L., Reignier, J., Ayzac, L., Loundou, A., Forel, J. M., Rolland-Debord, C., Bureau, C., Poitou, T., Clavel, M., Perbet, S., Terzi, N., Kouatchet, A., Similowski, T., Demoule, A., Hunfeld, N., Trogrlic, Z., Ladage, S., Osse, R. J., Koch, B., Rietdijk, W., Devlin, J., van der Jagt, M., Picetti, E., Ceccarelli, P., Mensi, F., Malchiodi, L., Risolo, S., Rossi, I., Antonini, M. V., Servadei, F., Caspani, M. L., Roquilly, A., Lasocki, S., Seguin, P., Geeraerts, T., Perrigault, P. F., Dahyot-Fizelier, C., Paugam-Burtz, C., Cook, F., Cinotti, R., dit Latte, D. Demeure, Mahe, P. J., Fortuit, C., Feuillet, F., Asehnoune, K., Marzorati, C., Spina, S., Scaravilli, V., Vargiolu, A., Riva, M., Giussani, C., Sganzerla, E., Citerio, G., Barbadillo, S., de Molina, F. J. González, Álvarez-Lerma, F., Rodríguez, A., Zakharkina, T., Martin-Loeches, I., Matamoros, S., Povoa, P., Torres, A., Kastelijn, J., Hofstra, J. J., de Jong, M., Schultz, M., Sterk, P., Artigas, A., Bos, L. J., Moreau, A. S., Martin-Loeches, I., Povoa, P., Salluh, J., Rodriguez, A., Nseir, S., de Jong, E., van Oers, J. A., Beishuizen, A., Girbes, A. R. J., Nijsten, M. W. N., de Lange, D. W., Bonvicini, D., Labate, D., Benacchio, L., Olivieri, A., Pizzirani, E., Lopez-Delgado, J. C., Gonzalez-Romero, M., Fuentes-Mila, V., Berbel-Franco, D., Romera-Peregrina, I., Martinez-Pascual, A., Perez-Sanchez, J., Abellan-Lencina, R., Ávila-Espinoza, R. E., Moreno-Gonzalez, G., Sbraga, F., Griffiths, S., Grocott, M. P. W., Creagh-Brown, B., Doyle, J., Wilkerson, P., Soon, Y., Huddart, S., Dickinson, M., Riga, A., Zuleika, A., Miyamoto, K., Kawazoe, Y., Morimoto, T., Yamamoto, T., Fuke, A., Hashimoto, A., Koami, H., Beppu, S., Katayama, Y., Ito, M., Ohta, Y., Yamamura, H., Rygård, S. L., Holst, L B., Wetterslev, J., Johansson, P. I., Perner, A., Soliman, I. W., de Lange, D. W., van Dijk, D., van Delden, J. J. M., Cremer, O. L., Slooter, A. J. C., Peelen, L. M., McWilliams, D., Snelson, C., Neves, A. Das, Loudet, C. I., Busico, M., Vazquez, D., Villalba, D., Veronesi, M., Lischinsky, A., López, F. J. L., Mori, L. Benito, Plotnikow, G., Díaz, A., Giannasi, S., Hernandez, R., Krzisnik, L., Cecotti, C., Viola, L., Lopez, R., Sottile, J. P., Benavent, G., Estenssoro, E., Chen, C. M., Lai, C. C., Cheng, K. C., Chou, W., Chan, K. S., Roeker, L. E., Horkan, C. M., Gibbons, F. K., Christopher, K. B., Weijs, P. J. M., Mogensen, K. M., Rawn, J. D., Robinson, M. K., Christopher, K. 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C., Vieira, Jr, J. M., Azevedo, L. C. P., Nurses of the Central and General ICUs of Shiraz Namazi Hospital, Sedation an Delirium Group Hospital Universitari de Bellvitge, SPACeR group (Surrey Peri-operative, Anaesthesia and Critical Care Collaborative Research Group), for the PRoVENT investigators and the PROVE Network, SEMICYUC/GETGAG Working Group, TAVeM study group, POPC-CB investigators, DESIRE (DExmedetomidine for Sepsis in ICU Randomized Evaluation) Trial Investigators, GEMINI, Bioethics work group of SEMICYUC, The FINNAKI Study Group, Queen Square Neuroanaesthesia and Neurocritical Care Resreach Group, Renal Transplantation HUVR, GEMINI, EDISVAL Group, EDISVAL Group, PLUG Working group, TAVeM study Group, The FINNAKI Study Group, on behalf of Department of Professional Development, ESICM, Critical Care Research Group, SIRAKI group, and Grupo ESBAGA
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- 2016
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23. Selenoprotein-P deficiency is associated with higher risk of incident heart failure
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Jujic, A, primary, Molvin, J, additional, Schomburg, L, additional, Struck, J, additional, Bergmann, A, additional, Melander, O, additional, and Magnusson, M, additional
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- 2022
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24. Biomarkers associated with prevalent hypertension and higher blood pressure in a population-based cohort: a proteomic approach
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Dieden, A, primary, Holm, H, additional, Melander, O, additional, Pareek, M, additional, Molvin, J, additional, Rastam, L, additional, Lindblad, U, additional, Daka, B, additional, Leosdottir, M, additional, Nilsson, P M, additional, Olsen, M H, additional, Gudmundsson, P, additional, Jujic, A, additional, and Magnusson, M, additional
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- 2022
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25. Vanin-1 T26I polymorphism, hypertension and cardiovascular events in two large urban-based prospective studies in Swedes
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Fava, C., Montagnana, M., Danese, E., Sjögren, M., Almgren, P., Engström, G., Hedblad, B., Guidi, G.C., Minuz, P., and Melander, O.
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- 2013
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26. SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe
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Hageman, S., Pennells, L., Ojeda, F., Kaptoge, S., Kuulasmaa, K., Vries, T. de, Xu, Z., Kee, F., Chung, R., Wood, A., McEvoy, J.W., Veronesi, G., Bolton, T., Dendale, P., Ference, B.A., Halle, M., Timmis, A., Vardas, P., Danesh, J., Graham, I., Salomaa, V., Visseren, F., Bacquer, D. de, Blankenberg, S., Dorresteijn, J., Angelantonio, E. di, Achenbach, S., Aleksandrova, K., Amiano, P., Amouyel, P., Andersson, J., Bakker, S.J.L., Costa, R.B.D., Beulens, J.W.J., Blaha, M., Bobak, M., Boer, J.M.A., Bonet, C., Bonnet, F., Boutron-Ruault, M.C., Braaten, T., Brenner, H., Brunner, F., Brunner, E.J., Brunstrom, M., Buring, J., Butterworth, A.S., Capkova, N., Cesana, G., Chrysohoou, C., Colorado-Yohar, S., Cook, N.R., Cooper, C., Dahm, C.C., Davidson, K., Dennison, E., Castelnuovo, A. di, Donfrancesco, C., Dorr, M., Dorynska, A., Eliasson, M., Engstrom, G., Ferrari, P., Ferrario, M., Ford, I., Fu, M., Gansevoort, R.T., Giampaoli, S., Gillum, R.F., Camara, A.G. de la, Grassi, G., Hansson, P.O., Huculeci, R., Hveem, K., Iacoviello, L., Ikram, M.K., Jorgensen, T., Joseph, B., Jousilahti, P., Jukema, J.W., Kaaks, R., Katzke, V., Kavousi, M., Kiechl, S., Klotsche, J., Konig, W., Kronmal, R.A., Kubinova, R., Kucharska-Newton, A., Lall, K., Lehmann, N., Leistner, D., Linneberg, A., Pablos, D.L., Lorenz, T., Lu, W.T., Luksiene, D., Lyngbakken, M., Magnussen, C., Malyutina, S., Ibanez, A.M., Masala, G., Mathiesen, E.B., Matsushita, K., Meade, T.W., Melander, O., Meyer, H.E., Moons, K.G.M., Moreno-Iribas, C., Muller, D., Munzel, T., Nikitin, Y., Nordestgaard, B.G., Omland, T., Onland, C., Overvad, K., Packard, C., Pajak, A., Palmieri, L., Panagiotakos, D., Panico, S., Perez-Cornago, A., Peters, A., Pietila, A., Pikhart, H., Psaty, B.M., Quarti-Trevano, F., Garcia, J.R.Q., Riboli, E., Ridker, P.M., Rodriguez, B., Rodriguez-Barranco, M., Rosengren, A., Roussel, R., Sacerdote, C., Sans, S., Sattar, N., Schiborn, C., Schmidt, B., Schottker, B., Schulze, M., Schwartz, J.E., Selmer, R.M., Shea, S., Shipley, M.J., Sieri, S., Soderberg, S., Sofat, R., Tamosiunas, A., Thorand, B., Tillmann, T., Tjonneland, A., Tong, T.Y.N., Trichopoulou, A., Tumino, R., Tunstall-Pedoe, H., Tybjaerg-Hansen, A., Tzoulaki, J., Heijden, A. van der, Schouw, Y.T. van der, Verschuren, W.M.M., Volzke, H., Waldeyer, C., Wareham, N.J., Weiderpass, E., Weidinger, F., Wild, P., Willeit, J., Willeit, P., Wilsgaard, T., Woodward, M., Zeller, T., Zhang, D.D., Zhou, B., SCORE2 Working Grp, ESC Cardiovasc Risk Collaboration, collaboration, SCORE2 working group and ESC Cardiovascular risk, Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Epidemiology, Neurology, Achenbach, S, Aleksandrova, K, Amiano, P, San Sebastian, D, Amouyel, P, Andersson, J, Bakker, S, Da Providencia Costa, R, Beulens, J, Blaha, M, Bobak, M, Boer, J, Bonet, C, Bonnet, F, Boutron-Ruault, M, Braaten, T, Brenner, H, Brunner, F, Brunner, E, Brunström, M, Buring, J, Butterworth, A, Capkova, N, Cesana, G, Chrysohoou, C, Colorado-Yohar, S, Cook, N, Cooper, C, Dahm, C, Davidson, K, Dennison, E, Di Castelnuovo, A, Donfrancesco, C, Dörr, M, Doryńska, A, Eliasson, M, Engström, G, Ferrari, P, Ferrario, M, Ford, I, Fu, M, Gansevoort, R, Giampaoli, S, Gillum, R, Gómez de la Cámara, A, Grassi, G, Hansson, P, Huculeci, R, Hveem, K, Iacoviello, L, Ikram, M, Jørgensen, T, Joseph, B, Jousilahti, P, Wouter Jukema, J, Kaaks, R, Katzke, V, Kavousi, M, Kiechl, S, Klotsche, J, König, W, Kronmal, R, Kubinova, R, Kucharska-Newton, A, Läll, K, Lehmann, N, Leistner, D, Linneberg, A, Pablos, D, Lorenz, T, Lu, W, Luksiene, D, Lyngbakken, M, Magnussen, C, Malyutina, S, Ibañez, A, Masala, G, Mathiesen, E, Matsushita, K, Meade, T, Melander, O, Meyer, H, Moons, K, Moreno-Iribas, C, Muller, D, Münzel, T, Nikitin, Y, Nordestgaard, B, Omland, T, Onland, C, Overvad, K, Packard, C, Pająk, A, Palmieri, L, Panagiotakos, D, Panico, S, Perez-Cornago, A, Peters, A, Pietilä, A, Pikhart, H, Psaty, B, Quarti-Trevano, F, Garcia, J, Riboli, E, Ridker, P, Rodriguez, B, Rodriguez-Barranco, M, Rosengren, A, Roussel, R, Sacerdote, C, S, S, Sattar, N, Schiborn, C, Schmidt, B, Schöttker, B, Schulze, M, Schwartz, J, Selmer, R, Shea, S, Shipley, M, Sieri, S, Söderberg, S, Sofat, R, Tamosiunas, A, Thorand, B, Tillmann, T, Tjønneland, A, Tong, T, Trichopoulou, A, Tumino, R, Tunstall-Pedoe, H, Tybjaerg-Hansen, A, Tzoulaki, J, van der Heijden, A, van der Schouw, Y, Verschuren, W, Völzke, H, Waldeyer, C, Wareham, N, Weiderpass, E, Weidinger, F, Wild, P, Willeit, J, Willeit, P, Wilsgaard, T, Woodward, M, Zeller, T, Zhang, D, Zhou, B, and Apollo - University of Cambridge Repository
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Male ,Cardiology ,RATIONALE ,Blood Pressure ,Disease ,030204 cardiovascular system & hematology ,PROFILE ,ACUTE CORONARY EVENTS ,VALIDATION ,Europe/epidemiology ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,DESIGN ,Clinical Research ,Risk Factors ,Diabetes mellitus ,medicine ,PARTICIPANTS ,Humans ,030212 general & internal medicine ,Risk factor ,Aged ,Primary prevention ,business.industry ,10-year CVD risk ,Incidence (epidemiology) ,Cardiovascular Diseases/epidemiology ,Risk Prediction ,Cardiovascular Disease ,Primary Prevention ,10-year Cvd Risk ,External validation ,PRIMARY-CARE ,Middle Aged ,medicine.disease ,Cardiovascular disease ,Risk prediction ,3. Good health ,Europe ,Prediction algorithms ,Blood pressure ,Cardiovascular Diseases ,Smoking status ,Female ,Cardiology and Cardiovascular Medicine ,business ,Algorithms ,Demography - Abstract
Aims The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40-69 years in Europe.Methods and results We derived risk prediction models using individual-participant data from 45 cohorts in 13 countries (677 684 individuals, 30 121 CVD events). We used sex-specific and competing risk-adjusted models, including age, smoking status, systolic blood pressure, and total- and HDL-cholesterol. We defined four risk regions in Europe according to country-specific CVD mortality, recalibrating models to each region using expected incidences and risk factor distributions. Region-specific incidence was estimated using CVD mortality and incidence data on 10 776 466 individuals. For external validation, we analysed data from 25 additional cohorts in 15 European countries (1 133 181 individuals, 43 492 CVD events). After applying the derived risk prediction models to external validation cohorts, C-indices ranged from 0.67 (0.65-0.68) to 0.81 (0.76-0.86). Predicted CVD risk varied several-fold across European regions. For example, the estimated 10-year CVD risk for a 50-year-old smoker, with a systolic blood pressure of 140 mmHg, total cholesterol of 5.5 mmol/L, and HDL-cholesterol of 1.3 mmol/L, ranged from 5.9% for men in low- risk countries to 14.0% for men in very high-risk countries, and from 4.2% for women in low-risk countries to 13.7% for women in very high-risk countries.Conclusion SCORE2-a new algorithm derived, calibrated, and validated to predict 10-year risk of first-onset CVD in European populations-enhances the identification of individuals at higher risk of developing CVD across Europe. Acknowledgements We thank investigators and participants of the several studies that contributed data to the Emerging Risk Factors Collaboration (ERFC). This research has been conducted using the UK Biobank Resource under Application Number 26865. Data from the Clinical Practice Research Datalink (CPRD) were obtained under licence from the UK Medicines and Healthcare products Regulatory Agency (protocol 162RMn2). CPRD uses data provided by patients and collected by the NHS as part of their care and support. We thank all EPIC participants and staff for their contribution to the study, the laboratory teams at the Medical Research Council Epidemiology Unit for sample management and Cambridge Genomic Services for genotyping, Sarah Spackman for data management and the team at the EPIC-CVD Coordinating Centre for study co-ordination and administration. Funding The ERFC co-ordinating centre was underpinned by programme grants from the British Heart Foundation (SP/09/002; RG/13/13/30194; RG/18/13/33946), BHF Centre of Research Excellence (RE/18/1/34212), the UK Medical Research Council (MR/L003120/1), and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC1215-20014), with project-specific support received from the UK NIHR [*], British United Provident Association UK Foundation and an unrestricted educational grant from GlaxoSmithKline. A variety of funding sources have supported recruitment, follow-up, and laboratory measurements in the studies contributing data to the ERFC, which are listed on the ERFC website (www.phpc.cam.ac.uk/ceu/erfc/list-of-studies). *The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation, and Wellcome. The MORGAM Project has received funding from EU projects MORGAM (Biomed BMH4-CT98-3183), GenomEUtwin (FP5, QLG2-CT-2002-01254), ENGAGE (FP7, HEALTH-F4-2007-201413),CHANCES (FP7, HEALTH-F3-2010-242244), BiomarCaRE (FP7,HEALTH-F2-2011-278913), euCanSHare (Horizon 2020, No. 825903) and AFFECT-EU (Horizon 2020, No. 847770); and Medical Research Council, London (G0601463, No. 80983: Biomarkers in the MORGAM Populations). This has supported central coordination, workshops and part of the activities of the MORGAM Data Centre, the MORGAM Laboratories and the MORGAM Participating Centres EPIC-CVD was funded by the European Research Council (268834), and the European Commission Framework Programme 7 (HEALTH-F2-2012-279233). This work was supported by the Estonian Research Council grant PUTs (PRG687, PUT1660, PUT1665, PRG184), by European Union through the European Regional Development Fund project no. MOBERA5 (Norface Network project no 462.16.107), by the Green ICT programme under Norway Grants 2014 – 2021 (grant number EU53928), by the European Union through Horizon 2020 grant no. 810645 and through the European Regional Development Fund (Project No. 2014-2020.4.01.16-0125) and by the PRECISE4Q consortium. PRECISE4Q project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement 777107. This work was partly funded through the CoMorMent project. CoMorMent has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement 847776. The KORA study was initiated and financed by the Helmholtz Zentrum Mu¨nchen—German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. The KORA study was supported by a research grant from the Virtual Institute of Diabetes Research (Helmholtz Zentrum Mu¨nchen), the Clinical Cooperation Group Diabetes between Ludwig-Maximilians-Universita¨t Mu¨nchen and Helmholtz Zentrum Mu¨nchen, and by the German Diabetes Center (DDZ). The HAPIEE project, Institute, was supported by grants from the Wellcome Trust (064947/Z/01/Z; WT081081) and US National Institute on Aging (1R01 and AG23522). The co-ordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Ge´ne´rale de l’Education Nationale, Institut National de la Sante´ et de la Recherche Me´dicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch 2448 SCORE2 working group and ESC Cardiovascular Risk Collaboration Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucı´a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Ska˚ne and Va¨sterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom)
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- 2021
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27. Vasopressin: novel roles for a new hormone – Emerging therapies in cardiometabolic and renal diseases
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Melander, O.
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- 2017
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28. [OP.7C.03] CHARACTERISTICS OF SUBJECTS AT LOWER END OF CAROTID-FEMORAL PULSE WAVE VELOCITY DISTRIBUTION, WHY ARE THEY HEALTHY?
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Gottsäter, M., Engström, G., Melander, O., and Nilsson, P.
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- 2017
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29. [OP.2A.08] RELATIONSHIP BETWEEN SELECTED DNA POLYMORPHISMS AND CORONARY ARTERY DISEASE COMPLICATIONS
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Wirtwein, M., Melander, O., Sjogren, M., Narkiewicz, K., Gruchala, M., and Sobiczewski, W.
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- 2017
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30. [OP.2A.01] IMPACT OF A 29 SNPS-BASED GENETIC RISK SCORE FOR HYPERTENSION ON AORTIC DISEASE
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Fava, C., Tagetti, A., Ohlsson, T., Engström, G., Smith, G., and Melander, O.
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- 2017
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31. Cardiovascular disease linked plasma proteins relate mainly to lung volumes
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Rydell, A, primary, Nerpin, E, additional, Zhou, X W, additional, Lind, L, additional, Lindberg, E, additional, Theorell Haglöw, J, additional, Fall, T, additional, Janson, C, additional, Lisspers, K, additional, Elmståhl, S, additional, Zaigham, S, additional, Melander, O, additional, Nilsson, P, additional, Orhu-Melander, M, additional, Ärnlöv, J, additional, and Malinovschi, A, additional
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- 2022
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32. Milk intake and incident stroke and coronary heart disease in populations of European descent : a mendelian randomization study
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Vissers, L.E.T., Sluijs, I., Burgess, S., Forouhi, N.G., Freisling, H., Imamura, F., Nilsson, Torbjörn K., Renström, Frida, Weiderpass, E., Aleksandrova, K., Dahm, C.C., Perez-Cornago, A., Schulze, M.B., Tong, T.Y.N., Aune, D., Bonet, C., Boer, J.M.A., Boeing, H., Chirlaque, M.D., Conchi, M.I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M.J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W.M.M., Riboli, E., Wareham, N.J., Danesh, J., Butterworth, A.S., Van Der Schouw, Y.T., Vissers, L.E.T., Sluijs, I., Burgess, S., Forouhi, N.G., Freisling, H., Imamura, F., Nilsson, Torbjörn K., Renström, Frida, Weiderpass, E., Aleksandrova, K., Dahm, C.C., Perez-Cornago, A., Schulze, M.B., Tong, T.Y.N., Aune, D., Bonet, C., Boer, J.M.A., Boeing, H., Chirlaque, M.D., Conchi, M.I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M.J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W.M.M., Riboli, E., Wareham, N.J., Danesh, J., Butterworth, A.S., and Van Der Schouw, Y.T.
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MEGASTROKE
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- 2022
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33. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses
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Gaziano, L, Sun, L, Arnold, M, Bell, S, Cho, K, Kaptoge, SK, Song, RJ, Burgess, S, Posner, DC, Mosconi, K, Robinson-Cohen, C, Mason, AM, Bolton, TR, Tao, R, Allara, E, Schubert, P, Chen, L, Staley, JR, Staplin, N, Altay, S, Amiano, P, Arndt, V, Ärnlöv, J, Barr, ELM, Björkelund, C, Boer, JMA, Brenner, H, Casiglia, E, Chiodini, P, Cooper, JA, Coresh, J, Cushman, M, Dankner, R, Davidson, KW, De Jongh, RT, Donfrancesco, C, Engström, G, Freisling, H, De La Cámara, AG, Gudnason, V, Hankey, GJ, Hansson, PO, Heath, AK, Hoorn, EJ, Imano, H, Jassal, SK, Kaaks, R, Katzke, V, Kauhanen, J, Kiechl, S, Koenig, W, Kronmal, RA, Kyrø, C, Lawlor, DA, Ljungberg, B, MacDonald, C, Masala, G, Meisinger, C, Melander, O, Moreno Iribas, C, Ninomiya, T, Nitsch, D, Nordestgaard, BG, Onland-Moret, C, Palmieri, L, Petrova, D, Garcia, JRQ, Rosengren, A, Sacerdote, C, Sakurai, M, Santiuste, C, Schulze, MB, Sieri, S, Sundström, J ; https://orcid.org/0000-0003-2247-8454, Tikhonoff, V, Tjønneland, A, Tong, T, Tumino, R, Tzoulaki, I, Van Der Schouw, YT, Monique Verschuren, WM, Völzke, H, Wallace, RB, Wannamethee, SG, Weiderpass, E, Willeit, P, Woodward, M ; https://orcid.org/0000-0001-9800-5296, Yamagishi, K, Zamora-Ros, R, Akwo, EA, Pyarajan, S, Gagnon, DR, Tsao, PS, Muralidhar, S, Edwards, TL, Damrauer, SM, Joseph, J, Pennells, L, Wilson, PWF, Harrison, S, Gaziano, L, Sun, L, Arnold, M, Bell, S, Cho, K, Kaptoge, SK, Song, RJ, Burgess, S, Posner, DC, Mosconi, K, Robinson-Cohen, C, Mason, AM, Bolton, TR, Tao, R, Allara, E, Schubert, P, Chen, L, Staley, JR, Staplin, N, Altay, S, Amiano, P, Arndt, V, Ärnlöv, J, Barr, ELM, Björkelund, C, Boer, JMA, Brenner, H, Casiglia, E, Chiodini, P, Cooper, JA, Coresh, J, Cushman, M, Dankner, R, Davidson, KW, De Jongh, RT, Donfrancesco, C, Engström, G, Freisling, H, De La Cámara, AG, Gudnason, V, Hankey, GJ, Hansson, PO, Heath, AK, Hoorn, EJ, Imano, H, Jassal, SK, Kaaks, R, Katzke, V, Kauhanen, J, Kiechl, S, Koenig, W, Kronmal, RA, Kyrø, C, Lawlor, DA, Ljungberg, B, MacDonald, C, Masala, G, Meisinger, C, Melander, O, Moreno Iribas, C, Ninomiya, T, Nitsch, D, Nordestgaard, BG, Onland-Moret, C, Palmieri, L, Petrova, D, Garcia, JRQ, Rosengren, A, Sacerdote, C, Sakurai, M, Santiuste, C, Schulze, MB, Sieri, S, Sundström, J ; https://orcid.org/0000-0003-2247-8454, Tikhonoff, V, Tjønneland, A, Tong, T, Tumino, R, Tzoulaki, I, Van Der Schouw, YT, Monique Verschuren, WM, Völzke, H, Wallace, RB, Wannamethee, SG, Weiderpass, E, Willeit, P, Woodward, M ; https://orcid.org/0000-0001-9800-5296, Yamagishi, K, Zamora-Ros, R, Akwo, EA, Pyarajan, S, Gagnon, DR, Tsao, PS, Muralidhar, S, Edwards, TL, Damrauer, SM, Joseph, J, Pennells, L, Wilson, PWF, and Harrison, S
- Abstract
Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches th
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34. Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
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Gorski, M, Rasheed, H, Teumer, A, Thomas, LF, Graham, SE, Sveinbjornsson, G, Winkler, TW, Günther, F, Stark, KJ, Chai, JF, Tayo, BO, Wuttke, M, Li, Y, Tin, A, Ahluwalia, TS, Ärnlöv, J, Åsvold, BO, Bakker, SJL, Banas, B, Bansal, N, Biggs, ML, Biino, G, Böhnke, M, Boerwinkle, E, Bottinger, EP, Brenner, H, Brumpton, B, Carroll, RJ, Chaker, L, Chalmers, J ; https://orcid.org/0000-0002-9931-0580, Chee, ML, Cheng, CY, Chu, AY, Ciullo, M, Cocca, M, Cook, JP, Coresh, J, Cusi, D, de Borst, MH, Degenhardt, F, Eckardt, KU, Endlich, K, Evans, MK, Feitosa, MF, Franke, A, Freitag-Wolf, S, Fuchsberger, C, Gampawar, P, Gansevoort, RT, Ghanbari, M, Ghasemi, S, Giedraitis, V, Gieger, C, Gudbjartsson, DF, Hallan, S, Hamet, P, Hishida, A, Ho, K, Hofer, E, Holleczek, B, Holm, H, Hoppmann, A, Horn, K, Hutri-Kähönen, N, Hveem, K, Hwang, SJ, Ikram, MA, Josyula, NS, Jung, B, Kähönen, M, Karabegović, I, Khor, CC, Koenig, W, Kramer, H, Krämer, BK, Kühnel, B, Kuusisto, J, Laakso, M, Lange, LA, Lehtimäki, T, Li, M, Lieb, W, Lind, L, Lindgren, CM, Loos, RJF, Lukas, MA, Lyytikäinen, LP, Mahajan, A, Matias-Garcia, PR, Meisinger, C, Meitinger, T, Melander, O, Milaneschi, Y, Mishra, PP, Mononen, N, Morris, AP, Mychaleckyj, JC, Nadkarni, GN, Naito, M, Woodward, Mark ; https://orcid.org/0000-0001-9800-5296, Gorski, M, Rasheed, H, Teumer, A, Thomas, LF, Graham, SE, Sveinbjornsson, G, Winkler, TW, Günther, F, Stark, KJ, Chai, JF, Tayo, BO, Wuttke, M, Li, Y, Tin, A, Ahluwalia, TS, Ärnlöv, J, Åsvold, BO, Bakker, SJL, Banas, B, Bansal, N, Biggs, ML, Biino, G, Böhnke, M, Boerwinkle, E, Bottinger, EP, Brenner, H, Brumpton, B, Carroll, RJ, Chaker, L, Chalmers, J ; https://orcid.org/0000-0002-9931-0580, Chee, ML, Cheng, CY, Chu, AY, Ciullo, M, Cocca, M, Cook, JP, Coresh, J, Cusi, D, de Borst, MH, Degenhardt, F, Eckardt, KU, Endlich, K, Evans, MK, Feitosa, MF, Franke, A, Freitag-Wolf, S, Fuchsberger, C, Gampawar, P, Gansevoort, RT, Ghanbari, M, Ghasemi, S, Giedraitis, V, Gieger, C, Gudbjartsson, DF, Hallan, S, Hamet, P, Hishida, A, Ho, K, Hofer, E, Holleczek, B, Holm, H, Hoppmann, A, Horn, K, Hutri-Kähönen, N, Hveem, K, Hwang, SJ, Ikram, MA, Josyula, NS, Jung, B, Kähönen, M, Karabegović, I, Khor, CC, Koenig, W, Kramer, H, Krämer, BK, Kühnel, B, Kuusisto, J, Laakso, M, Lange, LA, Lehtimäki, T, Li, M, Lieb, W, Lind, L, Lindgren, CM, Loos, RJF, Lukas, MA, Lyytikäinen, LP, Mahajan, A, Matias-Garcia, PR, Meisinger, C, Meitinger, T, Melander, O, Milaneschi, Y, Mishra, PP, Mononen, N, Morris, AP, Mychaleckyj, JC, Nadkarni, GN, Naito, M, and Woodward, Mark ; https://orcid.org/0000-0001-9800-5296
- Abstract
Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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- 2022
35. Genetically Determined Reproductive Aging and Coronary Heart Disease: A Bidirectional 2-sample Mendelian Randomization
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Dam, V. Onland-Moret, N.C. Burgess, S. Chirlaque, M.-D. Peters, S.A.E. Schuit, E. Tikk, K. Weiderpass, E. Oliver-Williams, C. Wood, A.M. Tjønneland, A. Dahm, C.C. Overvad, K. Boutron-Ruault, M.-C. Schulze, M.B. Trichopoulou, A. Ferrari, P. Masala, G. Krogh, V. Tumino, R. Matullo, G. Panico, S. Boer, J.M.A. Verschuren, W.M.M. Waaseth, M. PCrossed D sign©rez, M.J.S. Amiano, P. Imaz, L. Moreno-Iribas, C. Melander, O. Harlid, S. Nordendahl, M. Wennberg, P. Key, T.J. Riboli, E. Santiuste, C. Kaaks, R. Katzke, V. Langenberg, C. Wareham, N.J. Schunkert, H. Erdmann, J. Willenborg, C. Hengstenberg, C. Kleber, M.E. Delgado, G. März, W. Kanoni, S. Dedoussis, G. Deloukas, P. Nikpay, M. Mcpherson, R. Scholz, M. Teren, A. Butterworth, A.S. Van Der Schouw, Y.T. and Dam, V. Onland-Moret, N.C. Burgess, S. Chirlaque, M.-D. Peters, S.A.E. Schuit, E. Tikk, K. Weiderpass, E. Oliver-Williams, C. Wood, A.M. Tjønneland, A. Dahm, C.C. Overvad, K. Boutron-Ruault, M.-C. Schulze, M.B. Trichopoulou, A. Ferrari, P. Masala, G. Krogh, V. Tumino, R. Matullo, G. Panico, S. Boer, J.M.A. Verschuren, W.M.M. Waaseth, M. PCrossed D sign©rez, M.J.S. Amiano, P. Imaz, L. Moreno-Iribas, C. Melander, O. Harlid, S. Nordendahl, M. Wennberg, P. Key, T.J. Riboli, E. Santiuste, C. Kaaks, R. Katzke, V. Langenberg, C. Wareham, N.J. Schunkert, H. Erdmann, J. Willenborg, C. Hengstenberg, C. Kleber, M.E. Delgado, G. März, W. Kanoni, S. Dedoussis, G. Deloukas, P. Nikpay, M. Mcpherson, R. Scholz, M. Teren, A. Butterworth, A.S. Van Der Schouw, Y.T.
- Abstract
Background: Accelerated reproductive aging, in women indicated by early natural menopause, is associated with increased coronary heart disease (CHD) risk in observational studies. Conversely, an adverse CHD risk profile has been suggested to accelerate menopause. Objectives: To study the direction and evidence for causality of the relationship between reproductive aging and (non-)fatal CHD and CHD risk factors in a bidirectional Mendelian randomization (MR) approach, using age at natural menopause (ANM) genetic variants as a measure for genetically determined reproductive aging in women. We also studied the association of these variants with CHD risk (factors) in men. Design: Two-sample MR, using both cohort data as well as summary statistics, with 4 methods: simple and weighted median-based, standard inverse-variance weighted (IVW) regression, and MR-Egger regression. Participants: Data from EPIC-CVD and summary statistics from UK Biobank and publicly available genome-wide association studies were pooled for the different analyses. Main Outcome Measures: CHD, CHD risk factors, and ANM. Results: Across different methods of MR, no association was found between genetically determined reproductive aging and CHD risk in women (relative risk estimateIVW = 0.99; 95% confidence interval (CI), 0.97-1.01), or any of the CHD risk factors. Similarly, no associations were found in men. Neither did the reversed analyses show evidence for an association between CHD (risk factors) and reproductive aging. Conclusion: Genetically determined reproductive aging is not causally associated with CHD risk (factors) in women, nor were the genetic variants associated in men. We found no evidence for a reverse association in a combined sample of women and men. © 2022 The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.
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- 2022
36. Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants
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Aragam, K.G. Jiang, T. Goel, A. Kanoni, S. Wolford, B.N. Atri, D.S. Weeks, E.M. Wang, M. Hindy, G. Zhou, W. Grace, C. Roselli, C. Marston, N.A. Kamanu, F.K. Surakka, I. Venegas, L.M. Sherliker, P. Koyama, S. Ishigaki, K. Åsvold, B.O. Brown, M.R. Brumpton, B. de Vries, P.S. Giannakopoulou, O. Giardoglou, P. Gudbjartsson, D.F. Güldener, U. Haider, S.M.I. Helgadottir, A. Ibrahim, M. Kastrati, A. Kessler, T. Kyriakou, T. Konopka, T. Li, L. Ma, L. Meitinger, T. Mucha, S. Munz, M. Murgia, F. Nielsen, J.B. Nöthen, M.M. Pang, S. Reinberger, T. Schnitzler, G. Smedley, D. Thorleifsson, G. von Scheidt, M. Ulirsch, J.C. Danesh, J. Arnar, D.O. Burtt, N.P. Costanzo, M.C. Flannick, J. Ito, K. Jang, D.-K. Kamatani, Y. Khera, A.V. Komuro, I. Kullo, I.J. Lotta, L.A. Nelson, C.P. Roberts, R. Thorgeirsson, G. Thorsteinsdottir, U. Webb, T.R. Baras, A. Björkegren, J.L.M. Boerwinkle, E. Dedoussis, G. Holm, H. Hveem, K. Melander, O. Morrison, A.C. Orho-Melander, M. Rallidis, L.S. Ruusalepp, A. Sabatine, M.S. Stefansson, K. Zalloua, P. Ellinor, P.T. Farrall, M. Danesh, J. Ruff, C.T. Finucane, H.K. Hopewell, J.C. Clarke, R. Gupta, R.M. Erdmann, J. Samani, N.J. Schunkert, H. Watkins, H. Willer, C.J. Deloukas, P. Kathiresan, S. Butterworth, A.S. de Vries, P.S. von Scheidt, M. Biobank Japan EPIC-CVD The CARDIoGRAMplusC4D Consortium and Aragam, K.G. Jiang, T. Goel, A. Kanoni, S. Wolford, B.N. Atri, D.S. Weeks, E.M. Wang, M. Hindy, G. Zhou, W. Grace, C. Roselli, C. Marston, N.A. Kamanu, F.K. Surakka, I. Venegas, L.M. Sherliker, P. Koyama, S. Ishigaki, K. Åsvold, B.O. Brown, M.R. Brumpton, B. de Vries, P.S. Giannakopoulou, O. Giardoglou, P. Gudbjartsson, D.F. Güldener, U. Haider, S.M.I. Helgadottir, A. Ibrahim, M. Kastrati, A. Kessler, T. Kyriakou, T. Konopka, T. Li, L. Ma, L. Meitinger, T. Mucha, S. Munz, M. Murgia, F. Nielsen, J.B. Nöthen, M.M. Pang, S. Reinberger, T. Schnitzler, G. Smedley, D. Thorleifsson, G. von Scheidt, M. Ulirsch, J.C. Danesh, J. Arnar, D.O. Burtt, N.P. Costanzo, M.C. Flannick, J. Ito, K. Jang, D.-K. Kamatani, Y. Khera, A.V. Komuro, I. Kullo, I.J. Lotta, L.A. Nelson, C.P. Roberts, R. Thorgeirsson, G. Thorsteinsdottir, U. Webb, T.R. Baras, A. Björkegren, J.L.M. Boerwinkle, E. Dedoussis, G. Holm, H. Hveem, K. Melander, O. Morrison, A.C. Orho-Melander, M. Rallidis, L.S. Ruusalepp, A. Sabatine, M.S. Stefansson, K. Zalloua, P. Ellinor, P.T. Farrall, M. Danesh, J. Ruff, C.T. Finucane, H.K. Hopewell, J.C. Clarke, R. Gupta, R.M. Erdmann, J. Samani, N.J. Schunkert, H. Watkins, H. Willer, C.J. Deloukas, P. Kathiresan, S. Butterworth, A.S. de Vries, P.S. von Scheidt, M. Biobank Japan EPIC-CVD The CARDIoGRAMplusC4D Consortium
- Abstract
The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in the pathogenesis of CAD. We prioritized 220 candidate causal genes, combining eight complementary approaches, including 123 supported by three or more approaches. Using CRISPR–Cas9, we experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility. Our analysis identifies and systematically characterizes >250 risk loci for CAD to inform experimental interrogation of putative causal mechanisms for CAD. © 2022, The Author(s).
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- 2022
37. Milk intake and incident stroke and coronary heart disease in populations of European descent:A Mendelian Randomization study
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Vissers, L. E.T., Sluijs, I., Burgess, S., Forouhi, N. G., Freisling, H., Imamura, F., Nilsson, T. K., Renström, F., Weiderpass, E., Aleksandrova, K., Dahm, C. C., Perez-Cornago, A., Schulze, M. B., Tong, T. Y.N., Aune, D., Bonet, C., Boer, J. M.A., Boeing, H., Chirlaque, M. D., Conchi, M. I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M. J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W. M.M., Riboli, E., Wareham, N. J., Danesh, J., Butterworth, A. S., Van Der Schouw, Y. T., Vissers, L. E.T., Sluijs, I., Burgess, S., Forouhi, N. G., Freisling, H., Imamura, F., Nilsson, T. K., Renström, F., Weiderpass, E., Aleksandrova, K., Dahm, C. C., Perez-Cornago, A., Schulze, M. B., Tong, T. Y.N., Aune, D., Bonet, C., Boer, J. M.A., Boeing, H., Chirlaque, M. D., Conchi, M. I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M. J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W. M.M., Riboli, E., Wareham, N. J., Danesh, J., Butterworth, A. S., and Van Der Schouw, Y. T.
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- 2022
38. Stroke genetics informs drug discovery and risk prediction across ancestries
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Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, Vlieg, AVH, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianin, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Lopez, OL, Carty, CL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Mueller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, and Gravel, S
- Abstract
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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- 2022
39. Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
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Pervjakova, N. (Natalia), Moen, G.-H. (Gunn-Helen), Borges, M.-C. (Maria-Carolina), Ferreira, T. (Teresa), Cook, J. P. (James P.), Allard, C. (Catherine), Beaumont, R. N. (Robin N.), Canouil, M. (Mickael), Hatem, G. (Gad), Heiskala, A. (Anni), Joensuu, A. (Anni), Karhunen, V. (Ville), Kwak, S. H. (Soo Heon), Lin, F. T. (Frederick T. J.), Liu, J. (Jun), Rifas-Shiman, S. (Sheryl), Tam, C. H. (Claudia H.), Tam, W. H. (Wing Hung), Thorleifsson, G. (Gudmar), Andrew, T. (Toby), Auvinen, J. (Juha), Bhowmik, B. (Bishwajit), Bonnefond, A. (Amelie), Delahaye, F. (Fabien), Demirkan, A. (Ayse), Froguel, P. (Philippe), Haller-Kikkatalo, K. (Kadri), Hardardottir, H. (Hildur), Hummel, S. (Sandra), Hussain, A. (Akhtar), Kajantie, E. (Eero), Keikkala, E. (Elina), Khamis, A. (Amna), Lahti, J. (Jari), Lekva, T. (Tove), Mustaniemi, S. (Sanna), Sommer, C. (Christine), Tagoma, A. (Aili), Tzala, E. (Evangelia), Uibo, R. (Raivo), Vääräsmäki, M. (Marja), Villa, P. M. (Pia M.), Birkeland, K. I. (Kare, I), Bouchard, L. (Luigi), Duijn, C. M. (Cornelia M.), Finer, S. (Sarah), Groop, L. (Leif), Hamalainen, E. (Esa), Hayes, G. M. (Geoffrey M.), Hitman, G. A. (Graham A.), Jang, H. C. (Hak C.), Järvelin, M.-R. (Marjo-Riitta), Jenum, A. K. (Anne Karen), Laivuori, H. (Hannele), Ma, R. C. (Ronald C.), Melander, O. (Olle), Oken, E. (Emily), Park, K. S. (Kyong Soo), Perron, P. (Patrice), Prasad, R. B. (Rashmi B.), Qvigstad, E. (Elisabeth), Sebert, S. (Sylvain), Stefansson, K. (Kari), Steinthorsdottir, V. (Valgerdur), Tuomi, T. (Tiinamaija), Hivert, M.-F. (Marie-France), Franks, P. W. (Paul W.), McCarthy, M. I. (Mark, I), Lindgren, C. M. (Cecilia M.), Freathy, R. M. (Rachel M.), Lawlor, D. A. (Deborah A.), Morris, A. P. (Andrew P.), Magi, R. (Reedik), Pervjakova, N. (Natalia), Moen, G.-H. (Gunn-Helen), Borges, M.-C. (Maria-Carolina), Ferreira, T. (Teresa), Cook, J. P. (James P.), Allard, C. (Catherine), Beaumont, R. N. (Robin N.), Canouil, M. (Mickael), Hatem, G. (Gad), Heiskala, A. (Anni), Joensuu, A. (Anni), Karhunen, V. (Ville), Kwak, S. H. (Soo Heon), Lin, F. T. (Frederick T. J.), Liu, J. (Jun), Rifas-Shiman, S. (Sheryl), Tam, C. H. (Claudia H.), Tam, W. H. (Wing Hung), Thorleifsson, G. (Gudmar), Andrew, T. (Toby), Auvinen, J. (Juha), Bhowmik, B. (Bishwajit), Bonnefond, A. (Amelie), Delahaye, F. (Fabien), Demirkan, A. (Ayse), Froguel, P. (Philippe), Haller-Kikkatalo, K. (Kadri), Hardardottir, H. (Hildur), Hummel, S. (Sandra), Hussain, A. (Akhtar), Kajantie, E. (Eero), Keikkala, E. (Elina), Khamis, A. (Amna), Lahti, J. (Jari), Lekva, T. (Tove), Mustaniemi, S. (Sanna), Sommer, C. (Christine), Tagoma, A. (Aili), Tzala, E. (Evangelia), Uibo, R. (Raivo), Vääräsmäki, M. (Marja), Villa, P. M. (Pia M.), Birkeland, K. I. (Kare, I), Bouchard, L. (Luigi), Duijn, C. M. (Cornelia M.), Finer, S. (Sarah), Groop, L. (Leif), Hamalainen, E. (Esa), Hayes, G. M. (Geoffrey M.), Hitman, G. A. (Graham A.), Jang, H. C. (Hak C.), Järvelin, M.-R. (Marjo-Riitta), Jenum, A. K. (Anne Karen), Laivuori, H. (Hannele), Ma, R. C. (Ronald C.), Melander, O. (Olle), Oken, E. (Emily), Park, K. S. (Kyong Soo), Perron, P. (Patrice), Prasad, R. B. (Rashmi B.), Qvigstad, E. (Elisabeth), Sebert, S. (Sylvain), Stefansson, K. (Kari), Steinthorsdottir, V. (Valgerdur), Tuomi, T. (Tiinamaija), Hivert, M.-F. (Marie-France), Franks, P. W. (Paul W.), McCarthy, M. I. (Mark, I), Lindgren, C. M. (Cecilia M.), Freathy, R. M. (Rachel M.), Lawlor, D. A. (Deborah A.), Morris, A. P. (Andrew P.), and Magi, R. (Reedik)
- Abstract
Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 x 10-8) with GDM, mapping to/near MTNR1B (P = 4.3 x 10-54), TCF7L2 (P = 4.0 x 10-16), CDKAL1 (P = 1.6 x 10-14), CDKN2A-CDKN2B (P = 4.1 x 10-9) and HKDC1 (P = 2.9 x 10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.
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- 2022
40. Milk intake and incident stroke and CHD in populations of European descent: A Mendelian randomisation study
- Author
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Cardiovasculaire Epi Team 1, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Public Health Practice, Public Health Epidemiologie, Vissers, L. E.T., Sluijs, I., Burgess, S., Forouhi, N. G., Freisling, H., Imamura, F., Nilsson, T. K., Renström, F., Weiderpass, E., Aleksandrova, K., Dahm, C. C., Perez-Cornago, A., Schulze, M. B., Tong, T. Y.N., Aune, D., Bonet, C., Boeing, H., Chirlaque, M. D., Conchi, M. I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M. J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W. M.M., Riboli, E., Wareham, N. J., Danesh, J., Butterworth, A. S., Van Der Schouw, Y. T., Cardiovasculaire Epi Team 1, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Public Health Practice, Public Health Epidemiologie, Vissers, L. E.T., Sluijs, I., Burgess, S., Forouhi, N. G., Freisling, H., Imamura, F., Nilsson, T. K., Renström, F., Weiderpass, E., Aleksandrova, K., Dahm, C. C., Perez-Cornago, A., Schulze, M. B., Tong, T. Y.N., Aune, D., Bonet, C., Boeing, H., Chirlaque, M. D., Conchi, M. I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M. J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W. M.M., Riboli, E., Wareham, N. J., Danesh, J., Butterworth, A. S., and Van Der Schouw, Y. T.
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- 2022
41. Outcomes of primary vs. delayed strategy of implanting a cardiac monitor for unexplained syncope
- Author
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Yasa, E, Intzilakis, T, Ricci, F, Melander, O, Hamrefors, V, Sutton, R, and Fedorowski, A
- Subjects
orthostatic hypotension ,implantable loop recorder ,cardiac arrhythmias ,syncope ,autonomic nervous system ,1103 Clinical Sciences ,electrocardiographic monitoring ,cardiovascular autonomic testing ,pacemaker - Abstract
OBJECTIVE: Implantable cardiac monitors (ILR) have an important role in diagnosing unexplained syncope. However, outcomes of primary vs. delayed ILR implantation after initial syncope evaluation have not been explored. METHODS: A total of 1705 patients with unexplained syncope were prospectively enrolled in the SYSTEMA (Syncope Study of Unselected Population in Malmö) cohort. Patients who underwent cardiovascular autonomic testing (CAT) and ILR were grouped into those referred to CAT after ILR implantation (primary ILR) and those in whom ILR was indicated after CAT (post-CAT ILR). RESULTS: One-hundred-and-fifteen patients (6.7%) received ILRs. ILR recipients were older (58 vs. 52 years; p = 0.002), had more syncope recurrences (6 vs. 4; p < 0.001), more traumatic falls (72% vs. 53%; p < 0.001), and less prodrome (40% vs. 55%; p = 0.005) than patients without ILRs. During follow-up ≥16 months after ILR, 67 (58%) had normal sinus rhythm, 10 (8.7%) had sinus arrest, 10 (8.7%) AV-block, 13 (11.3%) atrial fibrillation, 9 (7.8%) supraventricular tachycardia, 4 (3.5%) sinus tachycardia and 2 (1.7%) ventricular tachycardia with clinical symptom reproduction. There were 52 patients (45%) in the primary-ILR group and 63 (55%) in the post-CAT ILR group. Proportions of negative ILR monitoring (17/52 vs. 25/63; p = 0.56) and pacemaker implantations (7/52 vs. 15/63; p = 0.23) did not differ between groups. Baseline ECG conduction disorders predicted pacemaker implantation (n = 11/17; odds ratio:10.6; 95%CI: 3.15-35.3; p < 0.001). CAT was more often positive (73% vs. 40%; p < 0.001) in primary-ILR group. CONCLUSIONS: Primary ILR implantation was associated with more positive CAT compared with delayed ILR implantation, but negative monitoring and pacemaker implantations were not different between groups. ECG conduction disorders predicted subsequent pacemaker implantation.
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- 2022
42. Iam hiQ—a novel pair of accuracy indices for imputed genotypes
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Rosenberger, A., Tozzi, V., Bickeböller, H., Hung, R.J., Christiani, D.C., Caporaso, N.E., Liu, G., Bojesen, S.E., Le Marchand, L., Albanes, D., Aldrich, M.C., Tardon, A., Fernández-Tardón, G., Rennert, G., Field, J.K., Davies, M., Liloglou, T., Kiemeney, L.A., Lazarus, P., Haugen, A., Zienolddiny, S., Lam, S., Schabath, M.B., Andrew, A.S., Duell, E.J., Arnold, S.M., Brunnström, H., Melander, O., Goodman, G.E., Chen, C., Doherty, J.A., Teare, M.D., Cox, A., Woll, P.J., Risch, A., Muley, T.R., Johansson, M., Brennan, P., Landi, M.T., Shete, S.S., and Amos, C.I.
- Abstract
Background\ud \ud Imputation of untyped markers is a standard tool in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However, high accuracy with which genotypes are imputed is fundamental. Several accuracy measures have been proposed and some are implemented in imputation software, unfortunately diversely across platforms. In the present paper, we introduce Iam hiQ, an independent pair of accuracy measures that can be applied to dosage files, the output of all imputation software. Iam (imputation accuracy measure) quantifies the average amount of individual-specific versus population-specific genotype information in a linear manner. hiQ (heterogeneity in quantities of dosages) addresses the inter-individual heterogeneity between dosages of a marker across the sample at hand.\ud \ud \ud \ud Results\ud \ud Applying both measures to a large case–control sample of the International Lung Cancer Consortium (ILCCO), comprising 27,065 individuals, we found meaningful thresholds for Iam and hiQ suitable to classify markers of poor accuracy. We demonstrate how Manhattan-like plots and moving averages of Iam and hiQ can be useful to identify regions enriched with less accurate imputed markers, whereas these regions would by missed when applying the accuracy measure info (implemented in IMPUTE2).\ud \ud \ud \ud Conclusion\ud \ud We recommend using Iam hiQ additional to other accuracy scores for variant filtering before stepping into the analysis of imputed GWAS data.
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- 2022
43. Bioactive adrenomedullin in sepsis patients in the emergency department is associated with mortality, organ failure and admission to intensive care
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Lundberg OHM, Rosenqvist M, Bronton K, Schulte J, Friberg H, Melander O
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- 2022
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44. Metabolome-Defined Obesity and the Risk of Future Type 2 Diabetes and Mortality
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Ottosson F, Smith E, Ericson U, Brunkwall L, Orho-Melander M, Di Somma S, Antonini P, Nilsson PM, Fernandez C, Melander O
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- 2022
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45. Gene variance in the nicotinic receptor cluster (CHRNA5-CHRNA3-CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers
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Halldén, S., Sjögren, M., Hedblad, B., Engström, G., Hamrefors, V., Manjer, J., and Melander, O.
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- 2016
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46. (379) - Monogenic and Polygenic Contributions to Early Onset Advanced Heart Failure Based on Whole Genome Sequencing
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Czuba, T., Gidlöf, O., Lundgren, J., Bollano, E., Hellberg, M., Celik, S., Pimpalwar, N., Rentzsch, P., Martorella, M., Gummessson, A., Melander, O., Albinsson, S., Dellgren, G., Borén, J., Jeppsson, A., Lumbers, T., Shah, S., Nilsson, J., Natarajan, P., Lappalainen, T., Levin, M., Ehrencrona, H., and Smith, J.
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- 2024
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47. Female Sex and Angiotensin-Converting Enzyme (ACE) Insertion/Deletion Polymorphism Amplify the Effects of Adiposity on Blood Pressure
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Chiriacò, Martina, primary, Tricò, Domenico, additional, Leonetti, Simone, additional, Petrie, John R., additional, Balkau, Beverley, additional, Højlund, Kurt, additional, Pataky, Zoltan, additional, Nilsson, Peter M, additional, Natali, Andrea, additional, Heine, R.J., additional, Dekker, J., additional, de Rooij, S., additional, Nijpels, G., additional, Boorsma, W., additional, Mitrakou, A., additional, Tournis, S., additional, Kyriakopoulou, K., additional, Thomakos, P., additional, Lalic, N., additional, Lalic, K., additional, Jotic, A., additional, Lukic, L., additional, Civcic, M., additional, Nolan, J., additional, Yeow, T.P., additional, Murphy, M., additional, DeLong, C., additional, Neary, G., additional, Colgan, M.P., additional, Hatunic, M., additional, Konrad, T., additional, Böhles, H., additional, Fuellert, S., additional, Baer, F., additional, Zuchhold, H., additional, Golay, A., additional, Harsch Bobbioni, E., additional, Barthassat, V., additional, Makoundou, V., additional, Lehmann, T.N.O., additional, Merminod, T., additional, Perry, C., additional, Neary, F., additional, MacDougall, C., additional, Shields, K., additional, Malcolm, L., additional, Laakso, M., additional, Salmenniemi, U., additional, Aura, A., additional, Raisanen, R., additional, Ruotsalainen, U., additional, Sistonen, T., additional, Laitinen, M., additional, Saloranta, H., additional, Coppack, S.W., additional, McIntosh, N., additional, Ross, J., additional, Pettersson, L., additional, Khadobaksh, P., additional, Laville, M., additional, Bonnet, F., additional, Brac de la Perriere, A., additional, Louche-Pelissier, C., additional, Maitrepierre, C., additional, Peyrat, J., additional, Beltran, S., additional, Serusclat, A., additional, Gabriel, R., additional, Sánchez, E.M., additional, Carraro, R., additional, Friera, A., additional, Novella, B., additional, Nilsson, P., additional, Persson, M., additional, Östling, G., additional, Melander, O., additional, Burri, P., additional, Piatti, P.M., additional, Monti, L.D., additional, Setola, E., additional, Galluccio, E., additional, Minicucci, F., additional, Colleluori, A., additional, Walker, M., additional, Ibrahim, I.M., additional, Jayapaul, M., additional, Carman, D., additional, Ryan, C., additional, Short, K., additional, McGrady, Y., additional, Richardson, D., additional, Beck-Nielsen, H., additional, Staehr, P., additional, Vestergaard, V., additional, Olsen, C., additional, Hansen, L., additional, Bolli, G.B., additional, Porcellati, F., additional, Fanelli, C., additional, Lucidi, P., additional, Calcinaro, F., additional, Saturni, A., additional, Ferrannini, E., additional, Muscelli, E., additional, Pinnola, S., additional, Kozakova, M., additional, Casolaro, A., additional, Astiarraga, B.D., additional, Mingrone, G., additional, Guidone, C., additional, Favuzzi, A., additional, Di Rocco, P., additional, Anderwald, C., additional, Bischof, M., additional, Promintzer, M., additional, Krebs, M., additional, Mandl, M., additional, Hofer, A., additional, Luger, A., additional, Waldhäusl, W., additional, Roden, M., additional, Dekker, J.M., additional, Mari, A., additional, Petrie, J., additional, Gaffney, P., additional, Boran, G., additional, Kok, A., additional, Patel, S., additional, Gastaldelli, A., additional, Ciociaro, D., additional, Guillanneuf, M.T., additional, Mhamdi, L., additional, Landucci, L., additional, Hills, S., additional, Mota, L., additional, Pacini, G., additional, Cavaggion, C., additional, Tura, A., additional, and Hills, S.A., additional
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- 2022
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48. Milk intake and incident stroke and coronary heart disease in populations of European descent: A Mendelian Randomization study
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Vissers, L.E.T., Sluijs, I., Burgess, S., Forouhi, N.G., Freisling, H., Imamura, F., Nilsson, Torbjörn K., Renström, Frida, Weiderpass, E., Aleksandrova, K., Dahm, C.C., Perez-Cornago, A., Schulze, M.B., Tong, T.Y.N., Aune, D., Bonet, C., Boer, J.M.A., Boeing, H., Chirlaque, M.D., Conchi, M.I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M.J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W.M.M., Riboli, E., Wareham, N.J., Danesh, J., Butterworth, A.S., and Van Der Schouw, Y.T.
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Näringslära ,Nutrition and Dietetics ,CHD ,Milk ,Mendelian Randomization ,dairy ,stroke - Abstract
Higher milk intake has been associated with a lower stroke risk, but not with risk of coronary heart disease (CHD). Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29,328 participants (4,611 stroke; 9,828 CHD) of the EPIC-CVD (8 European countries) and EPIC-NL case-cohort studies. rs4988235, a lactase persistence (LP) single nucleotide polymorphism which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777,024 participants (50,804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483,966 participants (61,612 cases) from CARDIoGRAM, UK Biobank and EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β=13.7 g/day; 95%CI: 8.4-19.1) and EPIC-NL (36.8 g/day; 20.0-53.5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/day 1.05; 95%CI: 0.94-1.16) or CHD (1.02; 0.96-1.08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (odds ratios 1.02; 0.99-1.05) or CHD (0.99; 0.95-1.03). Current Mendelian Randomization analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk. MEGASTROKE
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- 2021
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49. Inverse relationship between a genetic risk score of 31 BMI loci and weight change before and after reaching middle age
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Rukh, G, Ahmad, S, Ericson, U, Hindy, G, Stocks, T, Renström, F, Almgren, P, Nilsson, P M, Melander, O, Franks, P W, and Orho-Melander, M
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- 2016
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50. The Swedish CArdioPulmonary BioImage Study: objectives and design
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Bergström, G., Berglund, G., Blomberg, A., Brandberg, J., Engström, G., Engvall, J., Eriksson, M., de Faire, U., Flinck, A., Hansson, M. G., Hedblad, B., Hjelmgren, O., Janson, C., Jernberg, T., Johnsson, Å., Johansson, L., Lind, L., Löfdahl, C.-G., Melander, O., Östgren, C. J., Persson, A., Persson, M., Sandström, A., Schmidt, C., Söderberg, S., Sundström, J., Toren, K., Waldenström, A., Wedel, H., Vikgren, J., Fagerberg, B., and Rosengren, A.
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- 2015
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