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251. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice: Developed by the Task Force for cardiovascular disease prevention in clinical practice with representatives of the European Society of Cardiology and 12 medical societies With the special contribution of the European Association of Preventive Cardiology (EAPC)

Author

Visseren, Frank L J, Mach, François, Smulders, Yvo M, Carballo, David, Koskinas, Konstantinos C, Bäck, Maria, Benetos, Athanase, Biffi, Alessandro, Boavida, José-Manuel, Capodanno, Davide, Cosyns, Bernard, Crawford, Carolyn, Davos, Constantinos H, Desormais, Ileana, Angelantonio, Emanuele Di, Franco, Oscar H, Halvorsen, Sigrun, Hobbs, F D Richard, Hollander, Monika, and Jankowska, Ewa A

Published
2022
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254. Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales

Author

Knight, Rochelle, Walker, Venexia, Ip, Samantha, Cooper, Jennifer A., Bolton, Thomas, Keene, Spencer, Denholm, Rachel, Akbari, Ashley, Abbasizanjani, Hoda, Torabi, Fatemeh, Omigie, Efosa, Hollings, Sam, North, Teri-Louise, Toms, Renin, Jiang, Xiyun, Angelantonio, Emanuele Di, Denaxas, Spiros, Thygesen, Johan H., Tomlinson, Christopher, Bray, Ben, Smith, Craig J., Barber, Mark, Khunti, Kamlesh, Davey Smith, George, Chaturvedi, Nishi, Sudlow, Cathie, Whiteley, William N., Wood, Angela M., and Sterne, Jonathan A.C.

Published
2022
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255. COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

Author

Thygesen, Johan H, Tomlinson, Christopher, Hollings, Sam, Mizani, Mehrdad A, Handy, Alex, Akbari, Ashley, Banerjee, Amitava, Cooper, Jennifer, Lai, Alvina G, Li, Kezhi, Mateen, Bilal A, Sattar, Naveed, Sofat, Reecha, Torralbo, Ana, Wu, Honghan, Wood, Angela, Sterne, Jonathan A C, Pagel, Christina, Whiteley, William N, Sudlow, Cathie, Hemingway, Harry, Denaxas, Spiros, Abbasizanjani, Hoda, Ahmed, Nida, Ahmed, Badar, Akbari, Ashley, Akinoso-Imran, Abdul Qadr, Allara, Elias, Allery, Freya, Angelantonio, Emanuele Di, Ashworth, Mark, Ayyar-Gupta, Vandana, Babu-Narayan, Sonya, Bacon, Seb, Ball, Steve, Banerjee, Ami, Barber, Mark, Barrett, Jessica, Bennie, Marion, Berry, Colin, Beveridge, Jennifer, Birney, Ewan, Bojanić, Lana, Bolton, Thomas, Bone, Anna, Boyle, Jon, Braithwaite, Tasanee, Bray, Ben, Briffa, Norman, Brind, David, Brown, Katherine, Buch, Maya, Canoy, Dexter, Caputo, Massimo, Carragher, Raymond, Carson, Alan, Cezard, Genevieve, Chang, Jen-Yu Amy, Cheema, Kate, Chin, Richard, Chudasama, Yogini, Cooper, Jennifer, Copland, Emma, Crallan, Rebecca, Cripps, Rachel, Cromwell, David, Curcin, Vasa, Curry, Gwenetta, Dale, Caroline, Danesh, John, Das-Munshi, Jayati, Dashtban, Ashkan, Davies, Alun, Davies, Joanna, Davies, Gareth, Davies, Neil, Day, Joshua, Delmestri, Antonella, Denaxas, Spiros, Denholm, Rachel, Dennis, John, Denniston, Alastair, Deo, Salil, Dhillon, Baljean, Docherty, Annemarie, Dong, Tim, Douiri, Abdel, Downs, Johnny, Dregan, Alexandru, Ellins, Elizabeth A, Elwenspoek, Martha, Falck, Fabian, Falter, Florian, Fan, Yat Yi, Firth, Joseph, Fraser, Lorna, Friebel, Rocco, Gavrieli, Amir, Gerstung, Moritz, Gilbert, Ruth, Gillies, Clare, Glickman, Myer, Goldacre, Ben, Goldacre, Raph, Greaves, Felix, Green, Mark, Grieco, Luca, Griffiths, Rowena, Gurdasani, Deepti, Halcox, Julian, Hall, Nick, Hama, Tuankasfee, Handy, Alex, Hansell, Anna, Hardelid, Pia, Hardy, Flavien, Harris, Daniel, Harrison, Camille, Harron, Katie, Hassaine, Abdelaali, Hassan, Lamiece, Healey, Russell, Hemingway, Harry, Henderson, Angela, Herz, Naomi, Heyl, Johannes, Hidajat, Mira, Higginson, Irene, Hinchliffe, Rosie, Hippisley-Cox, Julia, Ho, Frederick, Hocaoglu, Mevhibe, Hollings, Sam, Horne, Elsie, Hughes, David, Humberstone, Ben, Inouye, Mike, Ip, Samantha, Islam, Nazrul, Jackson, Caroline, Jenkins, David, Jiang, Xiyun, Johnson, Shane, Kadam, Umesh, Kallis, Costas, Karim, Zainab, Kasan, Jake, Katsoulis, Michalis, Kavanagh, Kim, Kee, Frank, Keene, Spencer, Kent, Seamus, Khalid, Sara, Khawaja, Anthony, Khunti, Kamlesh, Killick, Richard, Kinnear, Deborah, Knight, Rochelle, Kolamunnage-Dona, Ruwanthi, Kontopantelis, Evan, Kurdi, Amanj, Lacey, Ben, Lai, Alvina, Lambarth, Andrew, Larzjan, Milad Nazarzadeh, Lawler, Deborah, Lawrence, Thomas, Lawson, Claire, Li, Qiuju, Li, Ken, Llinares, Miguel Bernabeu, Lorgelly, Paula, Lowe, Deborah, Lyons, Jane, Lyons, Ronan, Machado, Pedro, Macleod, Mary Joan, Macleod, John, Malgapo, Evaleen, Mamas, Mamas, Mamouei, Mohammad, Manohar, Sinduja, Mapeta, Rutendo, Martelli, Javiera Leniz, Martos, David Moreno, Mateen, Bilal, McCarthy, Aoife, Melville, Craig, Milton, Rebecca, Mizani, Mehrdad, Moncusi, Marta Pineda, Morales, Daniel, Mordi, Ify, Morrice, Lynn, Morris, Carole, Morris, Eva, Mu, Yi, Mueller, Tanja, Murdock, Lars, Nafilyan, Vahé, Nicholson, George, Nikiphorou, Elena, Nolan, John, Norris, Tom, Norris, Ruth, North, Laura, North, Teri-Louise, O'Connell, Dan, Oliver, Dominic, Oluyase, Adejoke, Olvera-Barrios, Abraham, Omigie, Efosa, Onida, Sarah, Padmanabhan, Sandosh, Palmer, Tom, Pasea, Laura, Patel, Riyaz, Payne, Rupert, Pell, Jill, Petitjean, Carmen, Pherwani, Arun, Pickrell, Owen, Pierotti, Livia, Pirmohamed, Munir, Priedon, Rouven, Prieto-Alhambra, Dani, Proudfoot, Alastair, Quinn, Terry, Quint, Jennifer, Raffetti, Elena, Rahimi, Kazem, Rao, Shishir, Razieh, Cameron, Roberts, Brian, Rogers, Caroline, Rossdale, Jennifer, Salim, Safa, Samani, Nilesh, Sattar, Naveed, Schnier, Christian, Schwartz, Roy, Selby, David, Seminog, Olena, Shabnam, Sharmin, Shah, Ajay, Shelton, Jon, Sheppard, James, Sinha, Shubhra, Skrypak, Mirek, Slapkova, Martina, Sleeman, Katherine, Smith, Craig, Sofat, Reecha, Sosenko, Filip, Sperrin, Matthew, Steeg, Sarah, Sterne, Jonathan, Stoica, Serban, Sudell, Maria, Sudlow, Cathie, Sun, Luanluan, Suseeladevi, Arun Karthikeyan, Sweeting, Michael, Sydes, Matt, Takhar, Rohan, Tang, Howard, Thygesen, Johan, Tilston, George, Tochel, Claire, Toit, Clea du, Tomlinson, Christopher, Toms, Renin, Torabi, Fatemeh, Torralbo, Ana, Townson, Julia, Tufail, Adnan, Tungamirai, Tapiwa, Varma, Susheel, Vollmer, Sebastian, Walker, Venexia, Wang, Tianxiao, Wang, Huan, Warwick, Alasdair, Watkinson, Ruth, Watson, Harry, Whiteley, William, Whittaker, Hannah, Wilde, Harry, Wilkinson, Tim, Williams, Gareth, Williams, Michelle, Williams, Richard, Withnell, Eloise, Wolfe, Charles, Wood, Angela, Wright, Lucy, Wu, Honghan, Wu, Jinge, Wu, Jianhua, Yates, Tom, Zaccardi, Francesco, Zhang, Haoting, Zhang, Huayu, and Zuccolo, Luisa

Abstract

Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework.

Published
2022
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256. Longer-term efficiency and safety of increasing the frequency of whole blood donation (INTERVAL): extension study of a randomised trial of 20 757 blood donors

Author

Kaptoge, Stephen, Di Angelantonio, Emanuele, Moore, Carmel, Walker, Matthew, Armitage, Jane, Ouwehand, Willem H, Roberts, David J, Danesh, John, Thompson, Simon G, Donovan, Jenny, Ford, Ian, Henry, Rachel, Hunt, Beverley J, le Huray, Bridget, Mehenny, Susan, Miflin, Gail, Green, Jane, Stredder, Mike, Watkins, Nicholas A, McDermott, Alan, Ronaldson, Clive, Thomson, Claire, Tolkien, Zoe, Williamson, Lorna, Allan, David, Sambrook, Jennifer, Hammerton, Tracey, Bruce, David, Choudry, Fizzah, Ghvaert, Cedric, Jonston, Kirstie, Kelly, Anne, King, Andrew, Mo, Alfred, Page, Lizanne, Richardson, Penny, Senior, Peter, Umrania, Yagnesh, Wong, Henna, Burchell, Brendan, Gallacher, John, Murphy, Gavin, Newland, Adrian C, Wheatley, Keith, Greaves, Michael, Turner, Marc, Aziz, Tahir, Brain, Richard, Davies, Christine, Turner, Ruth, Wakeman, Paula, Dent, Alison, Wakeman, Alan, Anthony, Ben, Bland, Desmond, Parrondo, Willem H, Vincent, Helen, Weatherill, Candy, Forsyth, Andrea, Butterfield, Carol, Wright, Tracey, Ellis, Karen, Johnston, Kristie, Poynton, Pat, Brooks, Carolyn, Martin, Emma, Littler, Lara, Williamson, Lindsay, Blair, Donna, Ackerley, Karen, Woods, Lynn, Stanley, Sophie, Walsh, Gemma, Franklin, Gayle, Howath, Cheryl, Sharpe, Sarah, Smith, Deborah, Botham, Lauren, Williams, Caroline, Alexander, Claire, Sowerbutts, Gareth, Furnival, Diane, Thake, Michael, Patel, Shilpa, Roost, Carolyn, Sowerby, Sandra, Appleton, Mary Joy, Bays, Eileen, Bowyer, Geoff, Clarkson, Steven, Halson, Stuart, Holmes, Kate, Humphreys, Gareth, Parvin-Cooper, Lee, Towler, Jason, Addy, Joanne, Barrass, Patrica, Stennett, Louise, Burton, Susan, Dingwell, Hannah, Clarke, Victoria, Potton, Maria, Bolton, Thomas, Daynes, Michael, Spackman, Sarah, Walker, Michael, Momodu, Abudu, Fenton, James, King, Adam, Muhammad, Omer, Oates, Nicholas, Peakman, Tim, Ryan, Christine, Spreckley, Kristian, Stubbins, Craig, Williams, Joanna, Brannan, James, Mochon, Cedric, Taylor, Samantha, Warren, Kimberly, and Mant, Jonathan

Subjects
R1
Abstract

Background: \ud The INTERVAL trial showed that, over a 2-year period, inter-donation intervals for whole blood donation can be safely reduced to meet blood shortages. We extended the INTERVAL trial for a further 2 years to evaluate the longer-term risks and benefits of varying inter-donation intervals, and to compare routine versus more intensive reminders to help donors keep appointments.\ud \ud Methods: \ud The INTERVAL trial was a parallel group, pragmatic, randomised trial that recruited blood donors aged 18 years or older from 25 static donor centres of NHS Blood and Transplant across England, UK. Here we report on the prespecified analyses after 4 years of follow-up. Participants were whole blood donors who agreed to continue trial participation on their originally allocated inter-donation intervals (men: 12, 10, and 8 weeks; women: 16, 14, and 12 weeks). They were further block-randomised (1:1) to routine versus more intensive reminders using computer-generated random sequences. The prespecified primary outcome was units of blood collected per year analysed in the intention-to-treat population. Secondary outcomes related to safety were quality of life, self-reported symptoms potentially related to donation, haemoglobin and ferritin concentrations, and deferrals because of low haemoglobin and other factors. This trial is registered with ISRCTN, number ISRCTN24760606, and has completed.\ud \ud Findings: \ud Between Oct 19, 2014, and May 3, 2016, 20 757 of the 38 035 invited blood donors (10 843 [58%] men, 9914 [51%] women) participated in the extension study. 10 378 (50%) were randomly assigned to routine reminders and 10 379 (50%) were randomly assigned to more intensive reminders. Median follow-up was 1·1 years (IQR 0·7–1·3). Compared with routine reminders, more intensive reminders increased blood collection by a mean of 0·11 units per year (95% CI 0·04–0·17; p=0·0003) in men and 0·06 units per year (0·01–0·11; p=0·0094) in women. During the extension study, each week shorter inter-donation interval increased blood collection by a mean of 0·23 units per year (0·21–0·25) in men and 0·14 units per year (0·12–0·15) in women (both p0.0001 for tests of linear trend by inter-donation intervals) other than a higher reported frequency of doctor-diagnosed low iron concentrations and prescription of iron supplements in men (p

Published
2019

257. Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease : A Prospective Study of 7198 Incident Cases Among 409 885 Participants in the Pan-European EPIC Cohort

Author

Key, Timothy J., Appleby, Paul N., Bradbury, Kathryn E., Sweeting, Michael, Wood, Angela, Johansson, Ingegerd, Kühn, Tilman, Steur, Marinka, Weiderpass, Elisabete, Wennberg, Maria, Lund Würtz, Anne Mette, Agudo, Antonio, Andersson, Jonas, Arriola, Larraitz, Boeing, Heiner, Boer, Jolanda M.A., Bonnet, Fabrice, Boutron-Ruault, Marie Christine, Cross, Amanda J., Ericson, Ulrika, Fagherazzi, Guy, Ferrari, Pietro, Gunter, Marc, Huerta, José María, Katzke, Verena, Khaw, Kay Tee, Krogh, Vittorio, La Vecchia, Carlo, Matullo, Giuseppe, Moreno-Iribas, Conchi, Naska, Androniki, Nilsson, Lena Maria, Olsen, Anja, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Molina-Portillo, Elena, Quirós, J. Ramón, Skeie, Guri, Sluijs, Ivonne, Sonestedt, Emily, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T., Verschuren, W. M.Monique, di Angelantonio, Emanuele, and Langenberg, Claudia

Subjects
Journal Article, food and beverages
Abstract

BACKGROUND: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition). METHODS: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates. RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06-1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89-0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86-0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88-0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-high-density lipoprotein cholesterol. CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects.

Published
2019

258. Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease:A Prospective Study of 7198 Incident Cases Among 409,885 Participants in the Pan-European EPIC Cohort

Author

Key, Timothy J, Appleby, Paul N, Bradbury, Kathryn E, Sweeting, Michael, Wood, Angela, Johansson, Ingegerd, Kühn, Tilman, Steur, Marinka, Weiderpass, Elisabete, Wennberg, Maria, Würtz, Anne Mette Lund, Agudo, Antonio, Andersson, Jonas, Arriola, Larraitz, Boeing, Heiner, Boer, Jolanda M A, Bonnet, Fabrice, Boutron-Ruault, Marie-Christine, Cross, Amanda J, Ericson, Ulrika, Fagherazzi, Guy, Ferrari, Pietro, Gunter, Marc, Huerta, José María, Katzke, Verena, Khaw, Kay-Tee, Krogh, Vittorio, La Vecchia, Carlo, Matullo, Giuseppe, Moreno-Iribas, Conchi, Naska, Androniki, Nilsson, Lena Maria, Olsen, Anja, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Molina-Portillo, Elena, Quirós, J Ramón, Skeie, Guri, Sluijs, Ivonne, Sonestedt, Emily, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T, Verschuren, W M Monique, Di Angelantonio, Emanuele, Langenberg, Claudia, Forouhi, Nita, Wareham, Nick, Butterworth, Adam, Riboli, Elio, and Danesh, John

Subjects
Male, Adult, VASCULAR MORTALITY, Eggs/adverse effects, Time Factors, Myocardial Ischemia/blood, BLOOD-PRESSURE, Blood Pressure, Meat/adverse effects, Recommended Dietary Allowances, Diet Surveys, Risk Assessment, Europe/epidemiology, meat, Risk Factors, eggs, Humans, Prospective Studies, Aged, fish, CALIBRATION, INDIVIDUAL DATA, Cholesterol, HDL/blood, heart diseases, dairy products, CHOLESTEROL, food and beverages, UPDATED METAANALYSIS, ASSOCIATION, Middle Aged, Protective Factors, CANCER, Cross-Sectional Studies, RED MEAT, Seafood/adverse effects, LIFE-STYLE, Female, Diet, Healthy, Dairy Products/adverse effects, Nutritive Value, Risk Reduction Behavior, Biomarkers/blood
Abstract

Background: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition). Methods: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates. Results: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06-1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89-0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86-0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88-0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-high-density lipoprotein cholesterol. Conclusions: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects.

Published
2019
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259. A catalog of genetic loci associated with kidney function from analyses of a million individuals

Author

Wuttke, Matthias, Li, Yong, Li, Man, Sieber, Karsten B., Feitosa, Mary F., Gorski, Mathias, Tin, Adrienne, Wang, Lihua, Chu, Audrey Y., Hoppmann, Anselm, Kirsten, Holger, Giri, Ayush, Chai, Jin-Fang, Sveinbjornsson, Gardar, Tayo, Bamidele O., Nutile, Teresa, Fuchsberger, Christian, Marten, Jonathan, Cocca, Massimiliano, Ghasemi, Sahar, Xu, Yizhe, Horn, Katrin, Noce, Damia, van der Most, Peter J., Sedaghat, Sanaz, Yu, Zhi, Akiyama, Masato, Afaq, Saima, Ahluwalia, Tarunveer S., Almgren, Peter, Amin, Najaf, Ärnlöv, Johan, Bakker, Stephan J. L., Bansal, Nisha, Baptista, Daniela, Bergmann, Sven, Biggs, Mary L., Biino, Ginevra, Boehnke, Michael, Boerwinkle, Eric, Boissel, Mathilde, Bottinger, Erwin P., Boutin, Thibaud S., Brenner, Hermann, Brumat, Marco, Burkhardt, Ralph, Butterworth, Adam S., Campana, Eric, Campbell, Archie, Campbell, Harry, Canouil, Mickaël, Carroll, Robert J., Catamo, Eulalia, Chambers, John C., Chee, Miao-Ling, Chee, Miao-Li, Chen, Xu, Cheng, Ching-Yu, Cheng, Yurong, Christensen, Kaare, Cifkova, Renata, Ciullo, Marina, Pina Concas, Maria, Cook, James P., Coresh, Josef, Corre, Tanguy, Sala, Cinzia Felicita, Cusi, Daniele, Danesh, John, Daw, E. Warwick, de Borst, Martin H., De Grandi, Alessandro, de Mutsert, Renée, de Vries, Aiko P. J., Degenhardt, Frauke, Delgado, Graciela, Demirkan, Ayse, Di Angelantonio, Emanuele, Dittrich, Katalin, Divers, Jasmin, Dorajoo, Rajkumar, Eckardt, Kai-Uwe, Ehret, Georg, Elliott, Paul, Endlich, Karlhans, Evans, Michele K., Felix, Janine F., Foo, Valencia Hui Xian, Franco, Oscar H., Franke, Andre, Freedman, Barry I., Freitag-Wolf, Sandra, Friedlander, Yechiel, Froguel, Philippe, Gansevoort, Ron T., Gao, He, Gasparini, Paolo, Gaziano, J. Michael, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Giulianini, Franco, Gögele, Martin, Gordon, Scott D., Gudbjartsson, Daniel F., Gudnason, Vilmundur, Haller, Toomas, Hamet, Pavel, Harris, Tamara B., Hartman, Catharina A., Hayward, Caroline, Hellwege, Jacklyn N., Heng, Chew-Kiat, Hickst, Andrew A., Hofer, Edith, Huang, Wei, Hutri-Kähönen, Nina, Hwang, Shih-Jen, ikram, M. Arfan, indridason, Olafur S., Ingelsson, Erik, ising, Marcus, Jaddoe, Vincent W. V., Jakobsdottir, Johanna, Jonas, Jost B, Joshi, Peter K., Shilpa Josyula, Navya, Jung, Bettina, Kähönen, Mika, Kamatani, Yoichiro, Kammerer, Candace M., Kanai, Masahiro, Kastarinen, Mika, Kerr, Shona M., Khor, Chiea-Chuen, Kiess, Wieland, Kleber, Marcus E., Koenig, Wolfgang, Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kraja, Aldi T., Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard K., Kronenberg, Florian, Kubo, Michiaki, Kühnel, Brigitte, Kuokkanen, Mikko, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lange, Leslie A., Langefeld, Carl D., Jen-Mai Lee, Jeannette, Lehne, Benjamin, Lehtimäki, Terho, Lieb, Wolfgang, Cohort Study, Lifelines, Lim, Su-Chi, Lind, Lars, Lindgren, Cecilia M., Liu, Jun, Liu, Jianjun, Loeffler, Markus, Loos, Ruth J. F., Lucae, Susanne, Ann Lukas, Mary, Lyytikäinen, Leo-Pekka, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Martins, Jade, März, Winfried, Mascalzoni, Deborah, Matsuda, Koichi, Christa Meisinger, Meitinger, Thomas, Melander, Olle, Metspalu, Andres, Mikaelsdottir, Evgenia K., Milaneschi, Yuri, Miliku, Kozeta, Mishra, Pashupati P., Veteran Program, V. A. Million, Mohlke, Karen L., Mononen, Nina, Montgomery, Grant W., Mook-Kanamori, Dennis O., Mychaleckyj, Josyf C., Nadkarni, Girish N, Nalls, Mike A., Nauck, Matthias, Nikus, Kjell, Ning, Boting, Nolte, ilja M., Noordam, Raymond, O’Connell, Jeffrey, O’Donoghue, Michelle L., Olafsson, Isleifur, Oldehinkel, Albertine J., Orho-Melander, Marju, Ouwehand, Willem H., Padmanabhan, Sandosh, Palmer, Nicholette D., Palsson, Runolfur, Penninx, Brenda W. J. H., Perls, Thomas, Perola, Markus, Pirastu, Mario, Pirastu, Nicola, Pistis, Giorgio, Podgornaia, Anna I., Polasek, Ozren, Ponte, Belen, Porteous, David J., Poulain, Tanja, Pramstaller, Peter P., Preuss, Michael H., Prins, Bram P., Province, Michael A., Rabelink, Ton J., Raffield, Laura M., Raitakari, Olli T., Reilly, Dermot F., Rettig, Rainer, Rheinberger, Myriam, Rice, Kenneth M., Ridker, Paul M., Rivadeneira, Fernando, Rizzi, Federica, Roberts, David J., Robino, Antonietta, Rossing, Peter, Rudan, Igor, Rueedi, Rico, Ruggiero, Daniela, Ryan, Kathleen A., Saba, Yasaman, Sabanayagam, Charumathi, Salomaa, Veikko, Salvi, Erika, Saum, Kai-Uwe, Schmidt, Helena, Schmidt, Reinhold, Schöttker, Ben, Schulz, Christina-Alexandra, Schupf, Nicole, Shaffer, Christian M., Shi, Yuan, Smith, Albert V., Smith, Blair H., Soranzo, Nicole, Spracklen, Cassandra N., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Svensson, Per O., Szymczak, Silke, Tai, E-Shyong, Tajuddin, Salman M., Tan, Nicholas Y. Q., Taylor, Kent D., Teren, Andrej, Tham, Yih-Chung, Thiery, Joachim, Thio, Chris H. L., Thomsen, Hauke, Thorleifsson, Gudmar, Toniolo, Daniela, Tönjes, Anke, Tremblay, Johanne, Tzoulaki, Ioanna, Uitterlinden, André G., Vaccargiu, Simona, van Dam, Rob M., van der Harst, Pim, van Duijn, Cornelia M., Velez Edward, Digna R., Verweij, Niek, Vogelezang, suzanne, Völker, üwe, Vollenweider, Peter, Waeber, Gerard, Waldenberger, Melanie, Wallentin, Lars, Wang, Ya Xing, Wang, Chaolong, Waterworth, Dawn M., Bin Wei, Wen, White, Harvey, Whitfield, John B., Wild, Sarah H., Wilson, James F., Wojczynski, Mary K., Wong, Charlene, Wong, Tien-Yin, Xu, Liang, Yang, Qiong, Yasuda, Masayuki, Yerges-Armstrong, Laura M., Zhang, Weihua, Zonderman, Alan B., Rotter, Jerome I., Bochud, Murielle, Psaty, Bruce M., Vitart, Veronique, Wilson, James G., Dehghan, Abbas, Parsa, Afshin, Chasman, Daniel I., Ho, Kevin, Morris, Andrew P., Devuyst, Olivier, Akilesh, Shreeram, Pendergrass, Sarah A., Sim, Xueling, Böger, Carsten A., Okada, Yukinori, Edwards, Todd L., Snieder, Harold, Stefansson, Kari, Hung, Adriana M., Heid, Iris M., Markus Scholz, Teumer, Alexander, Köttgen, Anna, Pattaro, Cristian, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Internal Medicine, Epidemiology, Erasmus MC other, Pediatrics, Psychiatry, APH - Mental Health, APH - Digital Health, Wuttke, M, Li, Y, Li, M, Sieber, Kb, Feitosa, Mf, Gorski, M, Tin, A, Wang, L, Chu, Ay, Hoppmann, A, Kirsten, H, Giri, A, Chai, Jf, Sveinbjornsson, G, Tayo, Bo, Nutile, T, Fuchsberger, C, Marten, J, Cocca, M, Ghasemi, S, Xu, Y, Horn, K, Noce, D, van der Most, Pj, Sedaghat, S, Yu, Z, Akiyama, M, Afaq, S, Ahluwalia, T, Almgren, P, Amin, N, Ärnlöv, J, Bakker, Sjl, Bansal, N, Baptista, D, Bergmann, S, Biggs, Ml, Biino, G, Boehnke, M, Boerwinkle, E, Boissel, M, Bottinger, Ep, Boutin, T, Brenner, H, Brumat, M, Burkhardt, R, Butterworth, A, Campana, Eric, Campbell, A, Campbell, H, Canouil, M, Carroll, Rj, Catamo, E, Chambers, Jc, Chee, Ml, Chen, X, Cheng, Cy, Cheng, Y, Christensen, K, Cifkova, R, Ciullo, M, Concas, Mp, Cook, Jp, Coresh, J, Corre, T, Sala, Cf, Cusi, D, Danesh, J, Daw, Ew, de Borst, Mh, De Grandi, A, de Mutsert, R, de Vries, Apj, Degenhardt, F, Delgado, G, Demirkan, A, Di Angelantonio, E, Dittrich, K, Divers, J, Dorajoo, R, Eckardt, Ku, Ehret, G, Elliott, P, Endlich, K, Evans, Mk, Felix, Jf, Foo, Vhx, Franco, Oh, Franke, A, Freedman, Bi, Freitag-Wolf, S, Friedlander, Y, Froguel, P, Gansevoort, Rt, Gao, H, Gasparini, P, Gaziano, Jm, Giedraitis, V, Gieger, C, Girotto, G, Giulianini, F, Gögele, M, Gordon, Sd, Gudbjartsson, Df, Gudnason, V, Haller, T, Hamet, P, Harris, Tb, Hartman, Ca, Hayward, C, Hellwege, Jn, Heng, Ck, Hicks, Aa, Hofer, E, Huang, W, Hutri-Kähönen, N, Hwang, Sj, Ikram, Ma, Indridason, O, Ingelsson, E, Ising, M, Jaddoe, Vwv, Jakobsdottir, J, Jonas, Jb, Joshi, Pk, Josyula, N, Jung, B, Kähönen, M, Kamatani, Y, Kammerer, Cm, Kanai, M, Kastarinen, M, Kerr, Sm, Khor, Cc, Kiess, W, Kleber, Me, Koenig, W, Kooner, J, Körner, A, Kovacs, P, Kraja, At, Krajcoviechova, A, Kramer, H, Krämer, Bk, Kronenberg, F, Kubo, M, Kühnel, B, Kuokkanen, M, Kuusisto, J, La Bianca, M, Laakso, M, Lange, La, Langefeld, Cd, Lee, Jj, Lehne, B, Lehtimäki, T, Lieb, W, Lifelines Cohort, Study, Lim, Sc, Lind, L, Lindgren, Cm, Liu, J, Loeffler, M, Loos, Rjf, Lucae, S, Lukas, Ma, Lyytikäinen, Lp, Mägi, R, Magnusson, Pke, Mahajan, A, Martin, Ng, Martins, J, März, W, Mascalzoni, D, Matsuda, K, Meisinger, C, Meitinger, T, Melander, O, Metspalu, A, Mikaelsdottir, Ek, Milaneschi, Y, Miliku, K, Mishra, Pp, V. A., Million Veteran Program, Mohlke, Kl, Mononen, N, Montgomery, Gw, Mook-Kanamori, Do, Mychaleckyj, Jc, Nadkarni, Gn, Nalls, Ma, Nauck, M, Nikus, K, Ning, B, Nolte, Im, Noordam, R, O'Connell, J, O'Donoghue, Ml, Olafsson, I, Oldehinkel, Aj, Orho-Melander, M, Ouwehand, Wh, Padmanabhan, S, Palmer, Nd, Palsson, R, Penninx, Bwjh, Perls, T, Perola, M, Pirastu, M, Pirastu, N, Pistis, G, Podgornaia, Ai, Polasek, O, Ponte, B, Porteous, Dj, Poulain, T, Pramstaller, Pp, Preuss, Mh, Prins, Bp, Province, Ma, Rabelink, Tj, Raffield, Lm, Raitakari, Ot, Reilly, Df, Rettig, R, Rheinberger, M, Rice, Km, Ridker, Pm, Rivadeneira, F, Rizzi, F, Roberts, Dj, Robino, A, Rossing, P, Rudan, I, Rueedi, R, Ruggiero, D, Ryan, Ka, Saba, Y, Sabanayagam, C, Salomaa, V, Salvi, E, Saum, Ku, Schmidt, H, Schmidt, R, Schöttker, B, Schulz, Ca, Schupf, N, Shaffer, Cm, Shi, Y, Smith, Av, Smith, Bh, Soranzo, N, Spracklen, Cn, Strauch, K, Stringham, Hm, Stumvoll, M, Svensson, Po, Szymczak, S, Tai, E, Tajuddin, Sm, Tan, Nyq, Taylor, Kd, Teren, A, Tham, Yc, Thiery, J, Thio, Chl, Thomsen, H, Thorleifsson, G, Toniolo, D, Tönjes, A, Tremblay, J, Tzoulaki, I, Uitterlinden, Ag, Vaccargiu, S, van Dam, Rm, van der Harst, P, van Duijn, Cm, Velez Edward, Dr, Verweij, N, Vogelezang, S, Völker, U, Vollenweider, P, Waeber, G, Waldenberger, M, Wallentin, L, Wang, Yx, Wang, C, Waterworth, Dm, Bin Wei, W, White, H, Whitfield, Jb, Wild, Sh, Wilson, Jf, Wojczynski, Mk, Wong, C, Wong, Ty, Xu, L, Yang, Q, Yasuda, M, Yerges-Armstrong, Lm, Zhang, W, Zonderman, Ab, Rotter, Ji, Bochud, M, Psaty, Bm, Vitart, V, Wilson, Jg, Dehghan, A, Parsa, A, Chasman, Di, Ho, K, Morris, Ap, Devuyst, O, Akilesh, S, Pendergrass, Sa, Sim, X, Böger, Ca, Okada, Y, Edwards, Tl, Snieder, H, Stefansson, K, Hung, Am, Heid, Im, Scholz, M, Teumer, A, Köttgen, A, and Pattaro, C.

Subjects
catalog, Inheritance Patterns, Hasso-Plattner-Institut für Digital Engineering GmbH, Genome-wide association study, Disease, Kidney Function Tests, Bioinformatics, DISEASE, 0302 clinical medicine, Uromodulin/urine, kidney function, 11 Medical and Health Sciences, Genetics & Heredity, ddc:616, 0303 health sciences, Kidney, Genome-wide association, HERITABILITY, GENOME-WIDE ASSOCIATION, COMMON VARIANTS, RENAL-FUNCTION, TRANS-EQTLS, METAANALYSIS, TRANSPORTER, CLASSIFICATION, INTEGRATION, Chromosome Mapping, 3. Good health, Phenotype, medicine.anatomical_structure, Medical genetics, Common variants, Renal function, Trans-EQTLS, Metaanalysis, Heritability, Transporter, Life Sciences & Biomedicine, Glomerular Filtration Rate, Metaanalysi, medicine.medical_specialty, Genotype, European Continental Ancestry Group, Quantitative Trait Loci, Common variant, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Article, White People, V. A. Million Veteran Program, 03 medical and health sciences, Quantitative Trait, Heritable, Lifelines Cohort Study, Uromodulin, Genetics, medicine, Humans, Genetic Predisposition to Disease, Renal Insufficiency, Chronic, Genetic Association Studies, 030304 developmental biology, Genetic association, Science & Technology, urogenital system, association, genetic loci, 06 Biological Sciences, medicine.disease, Renal Insufficiency, Chronic/genetics/physiopathology/urine, Genetic Association Studies/methods, ddc:000, 030217 neurology & neurosurgery, Developmental Biology, Genome-Wide Association Study, Kidney disease
Abstract

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

Published
2019
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260. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Author

Justice, Anne E, Karaderi, Tugce, Highland, Heather M, Young, Kristin L, Graff, Mariaelisa, Lu, Yingchang, Turcot, Valérie, Auer, Paul L, Fine, Rebecca S, Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W, Locke, Adam E, Medina-Gomez, Carolina, Esko, Tõnu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie CY, Heard-Costa, Nancy L, Feitosa, Mary F, Manning, Alisa K, Willems, Sara M, Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S, Allison, Matthew, Amouyel, Philippe, Arzumanyan, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Caulfield, Mark J, Cesana, Giancarlo, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Collins, Francis S, Cook, James P, Cox, Amanda J, Crosslin, David S, Danesh, John, de Bakker, Paul IW, Denus, Simon de, Mutsert, Renée de, Dedoussis, George, Demerath, Ellen W, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Dörr, Marcus, Drenos, Fotios, Dubé, Marie-Pierre, Dunning, Alison M, Easton, Douglas F, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C, Fornage, Myriam, Fox, Caroline S, Franks, Paul W, Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Grove, Megan L, Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, and Hattersley, Andrew T

Subjects
Male, ReproGen Consortium, Cardiovascular, Medical and Health Sciences, EPIC-CVD Consortium, Body Mass Index, MAGIC Investigators, Gene Frequency, Risk Factors, Clinical Research, Genetics, Animals, Humans, Homeostasis, Body Fat Distribution, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Exome, Global Lipids Genetic Consortium, Obesity, Aetiology, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, Metabolic and endocrine, Nutrition, CHD Exome+ Consortium, Waist-Hip Ratio, Prevention, Human Genome, Proteins, Genetic Variation, T2D-Genes Consortium, Biological Sciences, Lipids, GoT2D Genes Consortium, InterAct, Case-Control Studies, Drosophila, Female, ExomeBP Consortium, Genome-Wide Association Study, Biotechnology, Developmental Biology
Abstract

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF

Published
2019

261. Body mass index and all cause mortality in HUNT and UK Biobank studies: linear and non-linear mendelian randomisation analyses

Author

Sun, Yi-Qian, Burgess, Stephen, Staley, James R, Wood, Angela M, Bell, Steven, Kaptoge, Stephen K, Guo, Qi, Bolton, Thomas R, Mason, Amy M, Butterworth, Adam S, Di Angelantonio, Emanuele, Vie, Gunnhild Å, Bjørngaard, Johan H, Kinge, Jonas Minet, Chen, Yue, and Mai, Xiao-Mei

Subjects
Adult, Male, Norway, Research, nutritional and metabolic diseases, Mendelian Randomization Analysis, Middle Aged, United Kingdom, Body Mass Index, Thinness, Cardiovascular Diseases, Risk Factors, Cause of Death, Neoplasms, Humans, Female, Obesity, Sex Distribution, Aged
Abstract

Objective To investigate the shape of the causal relation between body mass index (BMI) and mortality. Design Linear and non-linear mendelian randomisation analyses. Setting Nord-Trøndelag Health (HUNT) Study (Norway) and UK Biobank (United Kingdom). Participants Middle to early late aged participants of European descent: 56 150 from the HUNT Study and 366 385 from UK Biobank. Main outcome measures All cause and cause specific (cardiovascular, cancer, and non-cardiovascular non-cancer) mortality. Results 12 015 and 10 344 participants died during a median of 18.5 and 7.0 years of follow-up in the HUNT Study and UK Biobank, respectively. Linear mendelian randomisation analyses indicated an overall positive association between genetically predicted BMI and the risk of all cause mortality. An increase of 1 unit in genetically predicted BMI led to a 5% (95% confidence interval 1% to 8%) higher risk of mortality in overweight participants (BMI 25.0-29.9) and a 9% (4% to 14%) higher risk of mortality in obese participants (BMI ≥30.0) but a 34% (16% to 48%) lower risk in underweight (BMI

Published
2019
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262. Consumption of Meat, Fish, Dairy Products, Eggs and Risk of Ischemic Heart Disease : A Prospective Study of 7198 Incident Cases Among 409,885 Participants in the Pan-European EPIC Cohort

Author

Key, Timothy J., Appleby, Paul N., Bradbury, Kathryn E., Sweeting, Michael, Wood, Angela, Johansson, Ingegerd, Kühn, Tilman, Steur, Marinka, Weiderpass, Elisabete, Wennberg, Maria, Würtz, Anne Mette Lund, Agudo, Antonio, Andersson, Jonas, Arriola, Larraitz, Boeing, Heiner, Boer, Jolanda M. A., Bonnet, Fabrice, Boutron-Ruault, Marie-Christine, Cross, Amanda J., Ericson, Ulrika, Fagherazzi, Guy, Ferrari, Pietro, Gunter, Marc, Huerta, José María, Katzke, Verena, Khaw, Kay-Tee, Krogh, Vittorio, La Vecchia, Carlo, Matullo, Giuseppe, Moreno-Iribas, Conchi, Naska, Androniki, Nilsson, Lena Maria, Olsen, Anja, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Molina-Portillo, Elena, Quirós, J. Ramón, Skeie, Guri, Sluijs, Ivonne, Sonestedt, Emily, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T., Verschuren, W. M. Monique, Di Angelantonio, Emanuele, Langenberg, Claudia, Forouhi, Nita, Wareham, Nick, Butterworth, Adam, Riboli, Elio, and Danesh, John

Subjects
fish, meat, Medicin och hälsovetenskap, dairy products, eggs, food and beverages, Medical and Health Sciences
Abstract

BACKGROUND: There is uncertainty about the relevance of animal foods to the etiology of ischemic heart disease (IHD). We examined meat, fish, dairy products and eggs and risk for IHD in the pan-European EPIC cohort. METHODS: A prospective study of 409,885 men and women in nine European countries. Diet was assessed using validated questionnaires, calibrated using 24-hour recalls. Lipids and blood pressure were measured in a subsample. During 12.6 years mean follow up, 7198 participants had a myocardial infarction or died from IHD. The relationships of animal foods with risk were examined using Cox regression with adjustment for other animal foods and relevant covariates. RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI 1.06-1.33) for a 100 g/d increment in intake of red and processed meat, and this remained significant after excluding the first 4 years of follow-up (HR 1.25 [1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR 0.93 [0.89-0.98] per 100 g/d increment), cheese (HR 0.92 [0.86-0.98] per 30 g/d increment) and eggs (HR 0.93 [0.88-0.99] per 20 g/d increment); the associations with yogurt and eggs were attenuated and non-significant after excluding the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish or milk. In analyses modelling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese or eggs was associated with approximately 20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-HDL cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-HDL cholesterol. CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat, and inversely associated with consumption of yogurt, cheese and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-HDL cholesterol, and for red and processed meat with systolic blood pressure, which could mediate such effects.

Published
2019

268. Publisher Correction : Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas G D, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie C Y, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Gonçalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der I, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul I W, Groot, Mark C H, Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, Heijer, Martin, Hollander, Anneke I, Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, Easton, Douglas F, Edwards, Todd L, Ellinghaus, David, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Farooqi, I Sadaf, Faul, Jessica D, Fauser, Sascha, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franco, Oscar H, Franke, Andre, Franks, Paul W, Friedrich, Nele, Frikke-Schmidt, Ruth, Galesloot, Tessel E, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Gibson, Jane, Giedraitis, Vilmantas, Gjesing, Anette P, Gordon-Larsen, Penny, Gorski, Mathias, Grabe, Hans-Jörgen, Grant, Struan F A, Grarup, Niels, Griffiths, Helen L, Grove, Megan L, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeff, Hakonarson, Hakon, Hammerschlag, Anke R, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Have, Christian T, Hayward, Caroline, He, Liang, Heard-Costa, Nancy L, Heath, Andrew C, Heid, Iris M, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W, Holmen, Oddgeir L, Hovingh, G Kees, Howson, Joanna M M, Hu, Yao, Huang, Paul L, Huffman, Jennifer E, Ikram, M Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Håkan, Jarvik, Gail P, Jensen, Gorm B, Jia, Yucheng, Johansson, Stefan, Jørgensen, Marit E, Jørgensen, Torben, Jukema, J Wouter, Kahali, Bratati, Kahn, René S, Kähönen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L R, Karpe, Fredrik, Kathiresan, Sekar, Kee, Frank, Kiemeney, Lambertus A, Kim, Eric, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S, Kooperberg, Charles, Korhonen, Tellervo, Kovacs, Peter, Kuivaniemi, Helena, Kutalik, Zoltán, Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A, Lamparter, David, Lange, Ethan M, Lange, Leslie A, Langenberg, Claudia, Larson, Eric B, Lee, Nanette R, Lehtimäki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Keng-Hung, Lin, Li-An, Lin, Xu, Lind, Lars, Lindström, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J, Liu, Yongmei, Lo, Ken S, Lophatananon, Artitaya, Lotery, Andrew J, Loukola, Anu, Luan, Jian'an, Lubitz, Steven A, Lyytikäinen, Leo-Pekka, Männistö, Satu, Marenne, Gaëlle, Mazul, Angela L, McCarthy, Mark I, McKean-Cowdin, Roberta, Medland, Sarah E, Meidtner, Karina, Milani, Lili, Mistry, Vanisha, Mitchell, Paul, Mohlke, Karen L, Moilanen, Leena, Moitry, Marie, Montgomery, Grant W, Mook-Kanamori, Dennis O, Moore, Carmel, Mori, Trevor A, Morris, Andrew D, Morris, Andrew P, Müller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Narisu, Narisu, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njølstad, Pål R, Nordestgaard, Børge G, Nyholt, Dale R, O'Connel, Jeffrey R, O'Donoghue, Michelle L, Loohuis, Loes M Olde, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin N A, Palmer, Nicholette D, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John R B, Pers, Tune H, Person, Thomas N, Peters, Annette, Petersen, Eva R B, Peyser, Patricia A, Pirie, Ailith, Polasek, Ozren, Polderman, Tinca J, Puolijoki, Hannu, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Renström, Frida, Rheinberger, Myriam, Ridker, Paul M, Rioux, John D, Rivas, Manuel A, Roberts, David J, Robertson, Neil R, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sapkota, Yadav, Sattar, Naveed, Schoen, Robert E, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati H, Sheu, Wayne H-H, Sim, Xueling, Slater, Andrew J, Small, Kerrin S, Smith, Albert V, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E, Strauch, Konstantin, Stringham, Heather M, Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swift, Amy J, Tada, Hayato, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H, Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, André G, Uusitupa, Matti, Laan, Sander W, Duijn, Cornelia M, Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Edwards, Digna R Velez, Vermeulen, Sita H, Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E, Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Ware, Erin B, Wareham, Nicholas J, Warren, Helen R, Waterworth, Dawn M, Wessel, Jennifer, White, Harvey D, Willer, Cristen J, Wilson, James G, Witte, Daniel R, Wood, Andrew R, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I, Pospisilik, John A, Rivadeneira, Fernando, Borecki, Ingrid B, Deloukas, 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Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H, Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, André G, Uusitupa, Matti, Laan, Sander W, Duijn, Cornelia M, Leeuwen, Nienke, van Setten, Jessica, Vanhala, Mauno, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Edwards, Digna R Velez, Vermeulen, Sita H, Veronesi, Giovanni, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Völker, Uwe, Vuckovic, Dragana, Wagenknecht, Lynne E, Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Ware, Erin B, Wareham, Nicholas J, Warren, Helen R, Waterworth, Dawn M, Wessel, Jennifer, White, Harvey D, Willer, Cristen J, Wilson, James G, Witte, Daniel R, Wood, Andrew R, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zhou, Wei, Zondervan, Krina T, Rotter, Jerome I, Pospisilik, John A, Rivadeneira, Fernando, Borecki, Ingrid B, Deloukas, Panos, Frayling, Timothy M, Lettre, Guillaume, North, Kari E, Lindgren, Cecilia M, Hirschhorn, Joel N, and Loos, Ruth J F

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019
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269. World Health Organization cardiovascular disease risk charts : revised models to estimate risk in 21 global regions

Author

Kaptoge, Stephen, Sundström, Johan, Di Angelantonio, Emanuele, Kaptoge, Stephen, Sundström, Johan, and Di Angelantonio, Emanuele

Abstract

Background: To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions. Methods: In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40–80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance. Findings: Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629–0·741) to 0·833 (0·783–0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a, The WHO CVD Risk Chart Working Group, for complete list of authors see http://dx.doi.org/10.1016/S2214-109X(19)30318-3

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2019
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270. Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution

Author

Justice, Anne E., Karaderi, Tugce, Highland, Heather M., Young, Kristin L., Graff, Mariaelisa, Lu, Yingchang, Turcot, Valerie, Auer, Paul L., Fine, Rebecca S., Guo, Xiuqing, Schurmann, Claudia, Lempradl, Adelheid, Marouli, Eirini, Mahajan, Anubha, Winkler, Thomas W., Locke, Adam E., Medina-Gomez, Carolina, Esko, Tonu, Vedantam, Sailaja, Giri, Ayush, Lo, Ken Sin, Alfred, Tamuno, Mudgal, Poorva, Ng, Maggie C. Y., Heard-Costa, Nancy L., Feitosa, Mary F., Manning, Alisa K., Willems, Sara M., Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S., Allison, Matthew, Amouyel, Philippe, Arzumanyanm, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Broer, Linda, Burt, Amber A., Butterworth, Adam S., Caulfield, Markj, Cesana, Giancarlo, Chambers, John C., Chasman, Daniel, I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audreyy, Collins, Francis S., Cook, James P., Cox, Amanda J., Crosslin, David S., Danesh, John, de Bakker, Paul I. W., de Denus, Simon, de Mutsert, Renee, Dedoussis, George, Demerath, Ellen W., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Doerr, Marcus, Drenos, Fotios, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Fornage, Myriam, Fox, Caroline S., Franks, Paul W., Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Groves, Megan L., Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, Hattersley, Andrew T., Hayward, Caroline, Heid, Iris M., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Hung, Yi-Jen, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jarvik, Gail P., Jia, Yucheng, Jorgensen, Torben, Jousilahti, Pekka, Justesen, Johanne M., Kahali, Bratati, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kovacs, Peter, Kraemer, Bernhard K., Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, La Nge, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lee, Wen-Jane, Lehtimaeki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, RuifangLi-Gao, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstroem, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Luan, Jian'an, Lyytikainen, Leo-Pekka, MacGregor, Stuart, Magi, Reedik, Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Mascal, Nicholas G. D., McCarthy, Mark, I, Meidtner, Karina, Mihailov, Evelin, Moilanen, Leena, Moitry, Marie, Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Ntalla, Ioanna, Owen, Katharine R., Pedersen, Oluf, Peloso, Gina M., Pennell, Craig E., Perola, Markus, James, A., Perry, John R. B., Pers, Tune H., Ewing, Ailith, Polasek, Ozren, Rasheed, Asif, Raulerson, Chelsea K., Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Ridker, Paul M., Rivas, Manuel A., Robertson, Neil R., Robino, Antonietta, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo, Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Blair H., Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swart, Karin M. A., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Torres, Mina, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van Duijn, Cornelia M., Vanhala, Mauno, Varma, Rohit, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wareham, N. Icholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Verges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Zillikens, M. Carola, Rivadeneira, Fernando, Borecki, Ingrid B., Pospisilik, J. 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Y., Heard-Costa, Nancy L., Feitosa, Mary F., Manning, Alisa K., Willems, Sara M., Sivapalaratnam, Suthesh, Abecasis, Goncalo, Alam, Dewan S., Allison, Matthew, Amouyel, Philippe, Arzumanyanm, Zorayr, Balkau, Beverley, Bastarache, Lisa, Bergmann, Sven, Bielak, Lawrence F., Blueher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A., Bork-Jensen, Jette, Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Broer, Linda, Burt, Amber A., Butterworth, Adam S., Caulfield, Markj, Cesana, Giancarlo, Chambers, John C., Chasman, Daniel, I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audreyy, Collins, Francis S., Cook, James P., Cox, Amanda J., Crosslin, David S., Danesh, John, de Bakker, Paul I. W., de Denus, Simon, de Mutsert, Renee, Dedoussis, George, Demerath, Ellen W., Dennis, Joe G., Denny, Josh C., Di Angelantonio, Emanuele, Doerr, Marcus, Drenos, Fotios, Dube, Marie-Pierre, Dunning, Alison M., Easton, Douglas F., Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Feng, Shuang, Ferrannini, Ele, Ferrieres, Jean, Florez, Jose C., Fornage, Myriam, Fox, Caroline S., Franks, Paul W., Friedrich, Nele, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Girotto, Giorgia, Gorski, Mathias, Grallert, Harald, Grarup, Niels, Groves, Megan L., Gustafsson, Stefan, Haessler, Jeff, Hansen, Torben, Hattersley, Andrew T., Hayward, Caroline, Heid, Iris M., Holmen, Oddgeir L., Hovingh, G. Kees, Howson, Joanna M. M., Hu, Yao, Hung, Yi-Jen, Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jarvik, Gail P., Jia, Yucheng, Jorgensen, Torben, Jousilahti, Pekka, Justesen, Johanne M., Kahali, Bratati, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Kitajima, Hidetoshi, Komulainen, Pirjo, Kooner, Jaspal S., Kovacs, Peter, Kraemer, Bernhard K., Kuulasmaa, Kari, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A., Lamparter, David, La Nge, Leslie A., Langenberg, Claudia, Larson, Eric B., Lee, Nanette R., Lee, Wen-Jane, Lehtimaeki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, RuifangLi-Gao, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstroem, Jaana, Linneberg, Allan, Liu, Ching-Ti, Liu, Dajiang J., Luan, Jian'an, Lyytikainen, Leo-Pekka, MacGregor, Stuart, Magi, Reedik, Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Mascal, Nicholas G. D., McCarthy, Mark, I, Meidtner, Karina, Mihailov, Evelin, Moilanen, Leena, Moitry, Marie, Mook-Kanamori, Dennis O., Morgan, Anna, Morris, Andrew P., Mueller-Nurasyid, Martina, Munroe, Patricia B., Narisu, Narisu, Nelson, Christopher P., Neville, Matt, Ntalla, Ioanna, Owen, Katharine R., Pedersen, Oluf, Peloso, Gina M., Pennell, Craig E., Perola, Markus, James, A., Perry, John R. B., Pers, Tune H., Ewing, Ailith, Polasek, Ozren, Rasheed, Asif, Raulerson, Chelsea K., Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Ridker, Paul M., Rivas, Manuel A., Robertson, Neil R., Robino, Antonietta, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura-Lepe, Marcelo, Sim, Xueling, Slater, Andrew J., Small, Kerrin S., Smith, Blair H., Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Stefansson, Kari, Steinthorsdottir, Valgerdur, Stirrups, Kathleen E., Strauch, Konstantin, Stringham, Heather M., Stumvoll, Michael, Sun, Liang, Surendran, Praveen, Swart, Karin M. A., Tardif, Jean-Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thuesen, Betina H., Toenjes, Anke, Torres, Mina, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van Duijn, Cornelia M., Vanhala, Mauno, Varma, Rohit, Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vuckovic, Dragana, Wagenknecht, Lynne E., Walker, Mark, Wallentin, Lars, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wareham, N. Icholas J., Warren, Helen R., Waterworth, Dawn M., Wessel, Jennifer, White, Harvey D., Willer, Cristen J., Wilson, James G., Wood, Andrew R., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Verges-Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Zillikens, M. Carola, Rivadeneira, Fernando, Borecki, Ingrid B., Pospisilik, J. Andrew, Deloukas, Panos, Frayling, Timothy M., Lettre, Guillaume, Mohlke, Karen L., Rotter, Jerome, I, Kutalik, Zoltan, Hirschhorn, Joel N., Cupples, L. Adrienne, Loos, Ruth J. F., North, Kari E., Lindgren, Cecilia M., O'Connell, Jeffrey R., Raitakari, Olli T., Lange, Leslie A., Uitterlinden, Andr G., Grove, Megan L., Masca, Nicholas G. D., Luan, Jianan, Wareham, Nicholas J., Esko, Tnu, De Bakker, Paul Iw, Caulfield, Mark J., and Mller-Nurasyid, Martina

Abstract

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

Published
2019
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271. Association of menopausal characteristics and risk of coronary heart disease : A pan-European case-cohort analysis

Author

Dam, Veerle, Van Der Schouw, Yvonne T., Onland-Moret, N. Charlotte, Groenwold, Rolf H.H., Peters, Sanne A.E., Burgess, Stephen, Wood, Angela M., Chirlaque, Maria Dolores, Moons, Karel G.M., Oliver-Williams, Clare, Schuit, Ewoud, Tikk, Kaja, Weiderpass, Elisabete, Holm, Marianne, Tjønneland, Anne, Kühn, Tilman, Fortner, Renée T., Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Ferrari, Pietro, Gunter, Marc, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Panico, Salvatore, Boer, Jolanda M.A., Monique Verschuren, W. M., Salamanca-Fernández, Elena, Arriola, Larraitz, Moreno-Iribas, Conchi, Engström, Gunnar, Melander, Olle, Nordendahl, Maria, Wennberg, Patrik, Key, Timothy J., Colorado-Yohar, Sandra, Matullo, Giuseppe, Overvad, Kim, Clavel-Chapelon, Francoise, Boeing, Heiner, Ramon Quiros, J., Di Angelantonio, Emanuele, Langenberg, Claudia, Sweeting, Michael J., Riboli, Elio, Wareham, Nicholas J., Danesh, John, Butterworth, Adam, Dam, Veerle, Van Der Schouw, Yvonne T., Onland-Moret, N. Charlotte, Groenwold, Rolf H.H., Peters, Sanne A.E., Burgess, Stephen, Wood, Angela M., Chirlaque, Maria Dolores, Moons, Karel G.M., Oliver-Williams, Clare, Schuit, Ewoud, Tikk, Kaja, Weiderpass, Elisabete, Holm, Marianne, Tjønneland, Anne, Kühn, Tilman, Fortner, Renée T., Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Ferrari, Pietro, Gunter, Marc, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Panico, Salvatore, Boer, Jolanda M.A., Monique Verschuren, W. M., Salamanca-Fernández, Elena, Arriola, Larraitz, Moreno-Iribas, Conchi, Engström, Gunnar, Melander, Olle, Nordendahl, Maria, Wennberg, Patrik, Key, Timothy J., Colorado-Yohar, Sandra, Matullo, Giuseppe, Overvad, Kim, Clavel-Chapelon, Francoise, Boeing, Heiner, Ramon Quiros, J., Di Angelantonio, Emanuele, Langenberg, Claudia, Sweeting, Michael J., Riboli, Elio, Wareham, Nicholas J., Danesh, John, and Butterworth, Adam

Published
2019

272. Consumption of Meat, Fish, Dairy Products, and Eggs and Risk of Ischemic Heart Disease: A Prospective Study of 7198 Incident Cases Among 409 885 Participants in the Pan-European EPIC Cohort

Author

UMC Utrecht, Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Public Health Epidemiologie, Key, Timothy J., Appleby, Paul N., Bradbury, Kathryn E., Sweeting, Michael, Wood, Angela, Johansson, Ingegerd, Kühn, Tilman, Steur, Marinka, Weiderpass, Elisabete, Wennberg, Maria, Lund Würtz, Anne Mette, Agudo, Antonio, Andersson, Jonas, Arriola, Larraitz, Boeing, Heiner, Boer, Jolanda M.A., Bonnet, Fabrice, Boutron-Ruault, Marie Christine, Cross, Amanda J., Ericson, Ulrika, Fagherazzi, Guy, Ferrari, Pietro, Gunter, Marc, Huerta, José María, Katzke, Verena, Khaw, Kay Tee, Krogh, Vittorio, La Vecchia, Carlo, Matullo, Giuseppe, Moreno-Iribas, Conchi, Naska, Androniki, Nilsson, Lena Maria, Olsen, Anja, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Molina-Portillo, Elena, Quirós, J. Ramón, Skeie, Guri, Sluijs, Ivonne, Sonestedt, Emily, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T., Verschuren, W. M.Monique, di Angelantonio, Emanuele, Langenberg, Claudia, UMC Utrecht, Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Public Health Epidemiologie, Key, Timothy J., Appleby, Paul N., Bradbury, Kathryn E., Sweeting, Michael, Wood, Angela, Johansson, Ingegerd, Kühn, Tilman, Steur, Marinka, Weiderpass, Elisabete, Wennberg, Maria, Lund Würtz, Anne Mette, Agudo, Antonio, Andersson, Jonas, Arriola, Larraitz, Boeing, Heiner, Boer, Jolanda M.A., Bonnet, Fabrice, Boutron-Ruault, Marie Christine, Cross, Amanda J., Ericson, Ulrika, Fagherazzi, Guy, Ferrari, Pietro, Gunter, Marc, Huerta, José María, Katzke, Verena, Khaw, Kay Tee, Krogh, Vittorio, La Vecchia, Carlo, Matullo, Giuseppe, Moreno-Iribas, Conchi, Naska, Androniki, Nilsson, Lena Maria, Olsen, Anja, Overvad, Kim, Palli, Domenico, Panico, Salvatore, Molina-Portillo, Elena, Quirós, J. Ramón, Skeie, Guri, Sluijs, Ivonne, Sonestedt, Emily, Stepien, Magdalena, Tjønneland, Anne, Trichopoulou, Antonia, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T., Verschuren, W. M.Monique, di Angelantonio, Emanuele, and Langenberg, Claudia

Published
2019

273. Association of menopausal characteristics and risk of coronary heart disease: A pan-European case-cohort analysis

Author

Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 3, JC onderzoeksprogramma Methodologie, Cardiovasculaire Epi Team 5, Epi Methoden, Epi Methoden Team 4, Public Health Epidemiologie, Dam, Veerle, Van Der Schouw, Yvonne T., Onland-Moret, N. Charlotte, Groenwold, Rolf H.H., Peters, Sanne A.E., Burgess, Stephen, Wood, Angela M., Chirlaque, Maria Dolores, Moons, Karel G.M., Oliver-Williams, Clare, Schuit, Ewoud, Tikk, Kaja, Weiderpass, Elisabete, Holm, Marianne, Tjønneland, Anne, Kühn, Tilman, Fortner, Renée T., Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Ferrari, Pietro, Gunter, Marc, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Panico, Salvatore, Boer, Jolanda M.A., Monique Verschuren, W. M., Salamanca-Fernández, Elena, Arriola, Larraitz, Moreno-Iribas, Conchi, Engström, Gunnar, Melander, Olle, Nordendahl, Maria, Wennberg, Patrik, Key, Timothy J., Colorado-Yohar, Sandra, Matullo, Giuseppe, Overvad, Kim, Clavel-Chapelon, Francoise, Boeing, Heiner, Ramon Quiros, J., Di Angelantonio, Emanuele, Langenberg, Claudia, Sweeting, Michael J., Riboli, Elio, Wareham, Nicholas J., Danesh, John, Butterworth, Adam, Cardiovasculaire Epi Team 1, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiovasculaire Epidemiologie, Cardiovasculaire Epi Team 3, JC onderzoeksprogramma Methodologie, Cardiovasculaire Epi Team 5, Epi Methoden, Epi Methoden Team 4, Public Health Epidemiologie, Dam, Veerle, Van Der Schouw, Yvonne T., Onland-Moret, N. Charlotte, Groenwold, Rolf H.H., Peters, Sanne A.E., Burgess, Stephen, Wood, Angela M., Chirlaque, Maria Dolores, Moons, Karel G.M., Oliver-Williams, Clare, Schuit, Ewoud, Tikk, Kaja, Weiderpass, Elisabete, Holm, Marianne, Tjønneland, Anne, Kühn, Tilman, Fortner, Renée T., Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Ferrari, Pietro, Gunter, Marc, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Panico, Salvatore, Boer, Jolanda M.A., Monique Verschuren, W. M., Salamanca-Fernández, Elena, Arriola, Larraitz, Moreno-Iribas, Conchi, Engström, Gunnar, Melander, Olle, Nordendahl, Maria, Wennberg, Patrik, Key, Timothy J., Colorado-Yohar, Sandra, Matullo, Giuseppe, Overvad, Kim, Clavel-Chapelon, Francoise, Boeing, Heiner, Ramon Quiros, J., Di Angelantonio, Emanuele, Langenberg, Claudia, Sweeting, Michael J., Riboli, Elio, Wareham, Nicholas J., Danesh, John, and Butterworth, Adam

Published
2019

274. Equalization of four cardiovascular risk algorithms after systematic recalibration:individual-participant meta-analysis of 86 prospective studies

Author

Pennells, Lisa, Kaptoge, Stephen, Wood, Angela, Sweeting, Mike, Zhao, Xiaohui, White, Ian, Burgess, Stephen, Willeit, Peter, Bolton, Thomas, Moons, Karel G. M., van der Schouw, Yvonne T., Selmer, Randi, Khaw, Kay-Tee, Gudnason, Vilmundur, Assmann, Gerd, Amouyel, Philippe, Salomaa, Veikko, Kivimaki, Mika, Nordestgaard, Borge G., Blaha, Michael J., Kuller, Lewis H., Brenner, Hermann, Gillum, Richard F., Meisinger, Christa, Ford, Ian, Knuiman, Matthew W., Rosengren, Annika, Lawlor, Debbie A., Volzke, Henry, Cooper, Cyrus, Ibanez, Alejandro Marin, Casiglia, Edoardo, Kauhanen, Jussi, Cooper, Jackie A., Rodriguez, Beatriz, Sundstrom, Johan, Barrett-Connor, Elizabeth, Dankner, Rachel, Nietert, Paul J., Davidson, Karina W., Wallace, Robert B., Blazer, Dan G., Bjorkelund, Cecilia, Donfrancesco, Chiara, Krumholz, Harlan M., Nissinen, Aulikki, Davis, Barry R., Coady, Sean, Whincup, Peter H., Jørgensen, Torben, Ducimetiere, Pierre, Trevisan, Maurizio, Engstrom, Gunnar, Crespo, Carlos J., Meade, Tomw., Visser, Marjolein, Kromhout, Daan, Kiechl, Stefan, Daimon, Makoto, Price, Jackie F., de la Camara, Agustin Gomez, Jukema, J. Wouter, Lamarche, Benoit, Onat, Altan, Simons, Leon A., Kavousi, Maryam, Ben-Shlomo, Yoav, Gallacher, John, Dekker, Jacqueline M., Arima, Hisatomi, Shara, Nawar, Tipping, RobertW., Roussel, Ronan, Brunner, Eric J., Koenig, Wolfgang, Sakurai, Masaru, Pavlovic, Jelena, Gansevoort, Ron T., Nagel, Dorothea, Goldbourt, Uri, Barr, Elizabeth L. M., Palmieri, Luigi, Njølstad, Inger, Sato, Shinichi, Verschuren, W. M. Monique, Varghese, Cherian V., Graham, Ian, Onuma, Oyere, Greenland, Philip, Woodward, Mark, Ezzati, Majid, Psaty, Bruce M., Sattar, Naveed, Jackson, Rod, Ridker, Paul M., Cook, Nancy, D'Agostino, Ralph B., Sr., Thompson, Simon G., Danesh, John, Di Angelantonio, Emanuele, Tipping, Robert W., Simpson, Lara M., Pressel, Sara L., Couper, David J., Nambi, Vijay, Matsushita, Kunihiro, Folsom, Aaron R., Shaw, Jonathan E., Magliano, Dianna J., Zimmet, Paul Z., Wannamethee, S. Goya, Willeit, Johann, Santer, Peter, Egger, Georg, Casas, Juan Pablo, Amuzu, Antointtte, Tikhonoff, Valerie, Sutherland, Susan E., Cushman, Mary, Sogaard, Anne Johanne, Haheim, Lise Lund, Ariansen, Inger, Tybjærg-Hansen, Anne, Jensen, Gorm B., Schnohr, Peter, Giampaoli, Simona, Vanuzzo, Diego, Panico, Salvatore, Balkau, Beverley, Bonnet, Fabrice, Marre, Michel, Herrera, Miguel Angel Rubio, Friedlander, Yechiel, McCallum, John, McLachlan, Stela, Guralnik, Jack, Phillips, Caroline L., Wareham, Nick, Schottker, Ben, Saum, Kai-Uwe, Holleczek, Bernd, Tolonen, Hanna, Jousilahti, Pekka, Harald, Kennet, Massaro, Joseph M., Pencina, Michael, Vasan, Ramachandran, Kayama, Takamasa, Kato, Takeo, Oizumi, Toshihide, Jespersen, Jorgen, Møller, Lars, Bladbjerg, Else Marie, Chetrit, A., Wilhelmsen, Lars, Lissner, Lauren, Dennison, Elaine, Kiyohara, Yutaka, Ninomiya, Toshiharu, Doi, Yasufumi, Nijpels, Giel, Stehouwer, Coen D. A., Kazumasa, Yamagishi, Iso, Hiroyasu, Vartiainen, Erkki, Kurl, Sudhir, Tuomainen, Tomi-Pekka, Salonen, Jukka T., Deeg, Dorly J. H., Nilsson, Peter M., Hedblad, Bo, Melander, Olle, De Boer, Ian H., DeFilippis, Andrew Paul, Watt, Graham, Verschuren, Monique, Tverdal, Aage, Kirkland, Susan, Shimbo, Daichi, Shaffer, Jonathan, Bakker, Stephan J. L., van der Harst, Pim, Hillege, Hans L., Dallongeville, Jean, Schulte, Helmut, Trompet, Stella, Smit, Roelof A. J., Stott, David J., Despres, Jean-Pierre, Cantin, Bernard, Dagenais, Gilles R., Laughlin, Gail, Wingard, Deborah, Aspelund, Thor, Eiriksdottir, Gudny, Gudmundsson, Elias Freyr, Ikram, Arfan, van Rooij, Frank J. A., Franco, Oscar H., Rueda-Ochoa, Oscar L., Muka, Taulant, Glisic, Marija, Tunstall-Pedoe, Hugh, Howard, Barbara V., Zhang, Ying, Jolly, Stacey, Davey-Smith, George, Can, Gunay, Yuksel, Husniye, Nakagawa, Hideaki, Morikawa, Yuko, Miura, Katsuyuki, Ingelsson, Martin, Giedraitis, Vilmantas, Gaziano, J. Michael, Shipley, Martin, Arndt, Volker, Geleijnse, Johanna M., Pennells, Lisa, Kaptoge, Stephen, Wood, Angela, Sweeting, Mike, Zhao, Xiaohui, White, Ian, Burgess, Stephen, Willeit, Peter, Bolton, Thomas, Moons, Karel G. M., van der Schouw, Yvonne T., Selmer, Randi, Khaw, Kay-Tee, Gudnason, Vilmundur, Assmann, Gerd, Amouyel, Philippe, Salomaa, Veikko, Kivimaki, Mika, Nordestgaard, Borge G., Blaha, Michael J., Kuller, Lewis H., Brenner, Hermann, Gillum, Richard F., Meisinger, Christa, Ford, Ian, Knuiman, Matthew W., Rosengren, Annika, Lawlor, Debbie A., Volzke, Henry, Cooper, Cyrus, Ibanez, Alejandro Marin, Casiglia, Edoardo, Kauhanen, Jussi, Cooper, Jackie A., Rodriguez, Beatriz, Sundstrom, Johan, Barrett-Connor, Elizabeth, Dankner, Rachel, Nietert, Paul J., Davidson, Karina W., Wallace, Robert B., Blazer, Dan G., Bjorkelund, Cecilia, Donfrancesco, Chiara, Krumholz, Harlan M., Nissinen, Aulikki, Davis, Barry R., Coady, Sean, Whincup, Peter H., Jørgensen, Torben, Ducimetiere, Pierre, Trevisan, Maurizio, Engstrom, Gunnar, Crespo, Carlos J., Meade, Tomw., Visser, Marjolein, Kromhout, Daan, Kiechl, Stefan, Daimon, Makoto, Price, Jackie F., de la Camara, Agustin Gomez, Jukema, J. Wouter, Lamarche, Benoit, Onat, Altan, Simons, Leon A., Kavousi, Maryam, Ben-Shlomo, Yoav, Gallacher, John, Dekker, Jacqueline M., Arima, Hisatomi, Shara, Nawar, Tipping, RobertW., Roussel, Ronan, Brunner, Eric J., Koenig, Wolfgang, Sakurai, Masaru, Pavlovic, Jelena, Gansevoort, Ron T., Nagel, Dorothea, Goldbourt, Uri, Barr, Elizabeth L. M., Palmieri, Luigi, Njølstad, Inger, Sato, Shinichi, Verschuren, W. M. Monique, Varghese, Cherian V., Graham, Ian, Onuma, Oyere, Greenland, Philip, Woodward, Mark, Ezzati, Majid, Psaty, Bruce M., Sattar, Naveed, Jackson, Rod, Ridker, Paul M., Cook, Nancy, D'Agostino, Ralph B., Sr., Thompson, Simon G., Danesh, John, Di Angelantonio, Emanuele, Tipping, Robert W., Simpson, Lara M., Pressel, Sara L., Couper, David J., Nambi, Vijay, Matsushita, Kunihiro, Folsom, Aaron R., Shaw, Jonathan E., Magliano, Dianna J., Zimmet, Paul Z., Wannamethee, S. Goya, Willeit, Johann, Santer, Peter, Egger, Georg, Casas, Juan Pablo, Amuzu, Antointtte, Tikhonoff, Valerie, Sutherland, Susan E., Cushman, Mary, Sogaard, Anne Johanne, Haheim, Lise Lund, Ariansen, Inger, Tybjærg-Hansen, Anne, Jensen, Gorm B., Schnohr, Peter, Giampaoli, Simona, Vanuzzo, Diego, Panico, Salvatore, Balkau, Beverley, Bonnet, Fabrice, Marre, Michel, Herrera, Miguel Angel Rubio, Friedlander, Yechiel, McCallum, John, McLachlan, Stela, Guralnik, Jack, Phillips, Caroline L., Wareham, Nick, Schottker, Ben, Saum, Kai-Uwe, Holleczek, Bernd, Tolonen, Hanna, Jousilahti, Pekka, Harald, Kennet, Massaro, Joseph M., Pencina, Michael, Vasan, Ramachandran, Kayama, Takamasa, Kato, Takeo, Oizumi, Toshihide, Jespersen, Jorgen, Møller, Lars, Bladbjerg, Else Marie, Chetrit, A., Wilhelmsen, Lars, Lissner, Lauren, Dennison, Elaine, Kiyohara, Yutaka, Ninomiya, Toshiharu, Doi, Yasufumi, Nijpels, Giel, Stehouwer, Coen D. A., Kazumasa, Yamagishi, Iso, Hiroyasu, Vartiainen, Erkki, Kurl, Sudhir, Tuomainen, Tomi-Pekka, Salonen, Jukka T., Deeg, Dorly J. H., Nilsson, Peter M., Hedblad, Bo, Melander, Olle, De Boer, Ian H., DeFilippis, Andrew Paul, Watt, Graham, Verschuren, Monique, Tverdal, Aage, Kirkland, Susan, Shimbo, Daichi, Shaffer, Jonathan, Bakker, Stephan J. L., van der Harst, Pim, Hillege, Hans L., Dallongeville, Jean, Schulte, Helmut, Trompet, Stella, Smit, Roelof A. J., Stott, David J., Despres, Jean-Pierre, Cantin, Bernard, Dagenais, Gilles R., Laughlin, Gail, Wingard, Deborah, Aspelund, Thor, Eiriksdottir, Gudny, Gudmundsson, Elias Freyr, Ikram, Arfan, van Rooij, Frank J. A., Franco, Oscar H., Rueda-Ochoa, Oscar L., Muka, Taulant, Glisic, Marija, Tunstall-Pedoe, Hugh, Howard, Barbara V., Zhang, Ying, Jolly, Stacey, Davey-Smith, George, Can, Gunay, Yuksel, Husniye, Nakagawa, Hideaki, Morikawa, Yuko, Miura, Katsuyuki, Ingelsson, Martin, Giedraitis, Vilmantas, Gaziano, J. Michael, Shipley, Martin, Arndt, Volker, and Geleijnse, Johanna M.

Published
2019

277. Risk factors for vasovagal reactions in blood donors: A systematic review and meta‐analysis.

Author

Wu, Yaning, Qi, Hongchao, Di Angelantonio, Emanuele, Kaptoge, Stephen, Wood, Angela M., and Kim, Lois G.

Abstract

Background Methods Results Conclusion While blood donation is generally safe, some donors experience vasovagal reactions (VVRs) that may lead to injury and reduce likelihood of future donation. Several risk factors for VVRs have been identified, but the consistency, magnitude, and validity of their associations have not been systematically evaluated. Therefore, this systematic review and meta‐analysis synthesized evidence for VVR risk factors.Database searches identified English‐language studies published before February 2024 describing VVR risk factors in voluntary whole blood donors. Study characteristics, VVR and risk factor assessment methods, and effect sizes were extracted. Random‐effects models pooled estimates across all studies and subgroups of geographical context, study quality, donation experience, and outcome severity. Inconsistently and infrequently reported risk factors were narratively synthesized.Totally 71 studies reporting a total of 19 million total donations were included. Female sex, new donor status, younger age, smaller blood volume, and lower blood pressure were positively associated with higher VVR risk. Donation‐related fear, anxiety, and disgust were associated with higher VVR risk in narrative syntheses. Substantial between‐study heterogeneity (I2 > 90%) was observed for the majority of risk factors, while there was no clear evidence of subgroup variability and small study effects.This systematic review and meta‐analysis provides a comprehensive synthesis of risk factors for VVRs across wide‐ranging blood service contexts and symptom severities, reinforcing evidence for previously identified factors. The heterogeneous associations of several risk factors motivate large‐scale studies that enable comprehensive multivariable adjustment to evidence donor selection criteria and preventative intervention allocation. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
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278. Association of shorter leucocyte telomere length with risk of frailty

Author

Bountziouka, Vasiliki, Nelson, Christopher P., Codd, Veryan, Wang, Qingning, Musicha, Crispin, Allara, Elias, Kaptoge, Stephen, Di Angelantonio, Emanuele, Butterworth, Adam S., Thompson, John R., Curtis, Elizabeth M., Wood, Angela M., Danesh, John N., Harvey, Nicholas C., Cooper, Cyrus, and Samani, Nilesh J.

Abstract

Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter‐individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty. We utilized cross‐sectional data from 441 781 UK Biobank participants (aged 40–69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single‐copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal. Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P= 2.73 × 10−33), more likely to be female (61%, P= 1.97 × 10−129), and had shorter LTL (−0.13SD vs. 0.03SD, P= 5.43 × 10−111) than non‐frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P= 3.99 × 10−12; 1.10 (1.08; 1.11) per SD shorter LTL, P= 1.46 × 10−30). Within each age group (40–49, 50–59, 60–69 years), the prevalence of frailty was about 33% higher in participants with shorter (−2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR‐Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P= 0.13). Inter‐individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.

Published
2022
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279. Body-mass index and all-cause mortality - Authors' reply

Author

Di Angelantonio, Emanuele, Bhupathiraju, Shilpa N, Hu, Frank B, Danesh, John, Peto, Richard, Lewington, Sarah, Global BMI Mortality Collaboration, Di Angelantonio, Emanuele [0000-0001-8776-6719], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository

Subjects
Humans, Obesity, Body Mass Index
Published
2017
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280. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis

Author

Schormair, Barbara, Zhao, Chen, Bell, Steven, Tilch, Erik, Salminen, Aaro V., Pütz, Benno, Dauvilliers, Yves, Stefani, Ambra, Högl, Birgit, Poewe, Werner, Kemlink, David, Sonka, Karel, Bachmann, Cornelius G., Paulus, Walter, Trenkwalder, Claudia, Oertel, Wolfgang H., Hornyak, Magdolna, Teder-Laving, Maris, Metspalu, Andres, Hadjigeorgiou, Georgios M., Polo, Olli, Fietze, Ingo, Ross, Owen A., Wszolek, Zbigniew, Butterworth, Adam S., Soranzo, Nicole, Ouwehand, Willem H., Roberts, David J., Danesh, John, Allen, Richard P., Earley, Christopher J., Ondo, William G., Xiong, Lan, Montplaisir, Jacques, Gan-Or, Ziv, Perola, Markus, Vodicka, Pavel, Dina, Christian, Franke, Andre, Tittmann, Lukas, Stewart, Alexandre F. R., Shah, Svati H., Gieger, Christian, Peters, Annette, Rouleau, Guy A., Berger, Klaus, Oexle, Konrad, Di Angelantonio, Emanuele, Hinds, David A., Müller-Myhsok, Bertram, Winkelmann, Juliane, Team, 23andMe Research, group, DESIR, Institute of Human Genetics, Technische Universität München [München] (TUM), Technische Universität München [München] (TUM)-German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Statistical Genetics Group, Metacohorts Consortium, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Department of Neurology, Innsbruck Medical University [Austria] (IMU), Charles University [Prague]-1st Faculty of Medicine, First Faculty of Medicine and General Teaching Hospital [Prague, Czech Republic], Charles university in Prague (CZECH REPUBLIC), Department of Clinical Neurophysiology [Göttingen], Georg-August-University [Göttingen], Paracelsus Elena Klinik, Centre for Parkinson's Disease & Movement Disorders, University of Tartu, Sleep Research Unit, University of Turku, Department of Pulmonary Medicine, Tampere University Hospital, Interdisciplinary Center of Sleep Medicine, Universitätsmedizin Berlin-Internetseiten der Charité, Centre for Molecular Medicine and Therapeutics, University of British Columbia (UBC), Department of Public Health & Primary Care, University of Cambridge [UK] (CAM), The Wellcome Trust Sanger Institute [Cambridge], Center of Excellence in Neuroscience, CHU de Montréal, Hôpital du Sacré-Coeur de Montréal, Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (ASCR), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Center For Narcolepsy, Stanford University [Stanford], Center of Excellence in Neuromics, University of Montreal, Institute of Human Genetics, Technische Universität München, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Bell, Steven [0000-0001-6774-3149], Butterworth, Adam [0000-0002-6915-9015], Soranzo, Nicole [0000-0003-1095-3852], Ouwehand, Willem [0000-0002-7744-1790], Danesh, John [0000-0003-1158-6791], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Charles University [Prague] (CU)-1st Faculty of Medicine, Charles University [Prague] (CU), Czech Academy of Sciences [Prague] (CAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Stanford University, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
DNA-Binding Proteins, Restless Legs Syndrome, [SDV]Life Sciences [q-bio], European Continental Ancestry Group, Humans, Genetic Predisposition to Disease, Nerve Tissue Proteins, Semaphorins, GPI-Linked Proteins, Transcription Factors, Genome-Wide Association Study
Abstract

International audience; BACKGROUND: Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. METHODS: In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15 126 cases and 95 725 controls of European ancestry. We identified common variants by fixed-effect inverse-variance meta-analysis. Significant genome-wide signals (p≤5 × 10(-8)) were tested for replication in an independent GWAS of 30 770 cases and 286 913 controls, followed by a joint analysis of the discovery and replication stages. We did gene annotation, pathway, and gene-set-enrichment analyses and studied the genetic correlations between restless legs syndrome and traits of interest. FINDINGS: We identified and replicated 13 new risk loci for restless legs syndrome and confirmed the previously identified six risk loci. MEIS1 was confirmed as the strongest genetic risk factor for restless legs syndrome (odds ratio 1·92, 95% CI 1·85-1·99). Gene prioritisation, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance (associated with SEMA6D), synapse formation (NTNG1), and neuronal specification (HOXB cluster family and MYT1). INTERPRETATION: Identification of new candidate genes and associated pathways will inform future functional research. Advances in understanding of the molecular mechanisms that underlie restless legs syndrome could lead to new treatment options. We focused on common variants; thus, additional studies are needed to dissect the roles of rare and structural variations. FUNDING: Deutsche Forschungsgemeinschaft, Helmholtz Zentrum München-Deutsches Forschungszentrum für Gesundheit und Umwelt, National Research Institutions, NHS Blood and Transplant, National Institute for Health Research, British Heart Foundation, European Commission, European Research Council, National Institutes of Health, National Institute of Neurological Disorders and Stroke, NIH Research Cambridge Biomedical Research Centre, and UK Medical Research Council.

Published
2017
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281. Rare and low-frequency coding variants alter human adult height

Author

Marouli, Eirini, Graff, Mariaelisa, Medina-Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R, Kjaer, Troels R, Fine, Rebecca S, Lu, Yingchang, Schurmann, Claudia, Highland, Heather M, Rueger, Sina, Thorleifsson, Gudmar, Justice, Anne E, Lamparter, David, Stirrups, Kathleen E, Turcot, Valerie, Young, Kristin L, Winkler, Thomas W, Esko, Tonu, Karaderi, Tugce, Locke, Adam E, Masca, Nicholas GD, Ng, Maggie CY, Mudgal, Poorva, Rivas, Manuel A, Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K, Adair, Linda S, Alam, Dewan S, Albrecht, Eva, Allin, Kristine H, Allison, Matthew, Amouyel, Philippe, Appel, Emil V, Arveiler, Dominique, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Banas, Bernhard, Bang, Lia E, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blueher, Matthias, Boeing, Heiner, Boerwinkle, Eric, Boeger, Carsten A, Bonnycastle, Lori L, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Burt, Amber A, Butterworth, Adam S, Carey, David J, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Galbany, Jordi Corominas, Cox, Amanda J, Cuellar-Partida, Gabriel, Danesh, John, Davies, Gail, de Bakker, Paul IW, de Borst, Gert J, de Denus, Simon, de Groot, Mark CH, de Mutsert, Renee, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, den Hollander, Anneke I, Dennis, Joe G, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dunning, Alison M, Easton, Douglas F, Ebeling, Tapani, Edwards, Todd L, Ellinor, Patrick T, Elliott, Paul, Evangelou, Evangelos, Farmaki, Aliki-Eleni, Faul, Jessica D, Feitosa, Mary F, Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M, Ferrieres, Jean, Florez, Jose C, Ford, Ian, Fornage, Myriam, Franks, Paul W, Frikke-Schmidt, Ruth, Galesloot, Tessel E, Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D, Gordon-Larsen, Penny, Gorski, Mathias, Grarup, Niels, Grove, Megan L, Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B, Hattersley, Andrew T, Hayward, Caroline, He, Liang, Heid, Iris M, Heikkila, Kauko, Helgeland, Oyvind, Hernesniemi, Jussi, Hewitt, Alex W, Hocking, Lynne J, Hollensted, Mette, Holmen, Oddgeir L, Hovingh, G Kees, Howson, Joanna MM, Hoyng, Carel B, Huang, Paul L, Hveem, Kristian, Ikram, M Arfan, Ingelsson, Erik, Jackson, Anne U, Jansson, Jan-Hakan, Jarvik, Gail P, Jensen, Gorm B, Jhun, Min A, Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jorgensen, Marit E, Jorgensen, Torben, Jousilahti, Pekka, Jukema, J Wouter, Kahali, Bratati, Kahn, Rene S, Kahonen, Mika, Kamstrup, Pia R, Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon LR, Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A, Kitajima, Hidetoshi, Kluivers, Kirsten B, Kocher, Thomas, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Kury, Sebastien, Kuusisto, Johanna, La Bianca, Martina, Laakso, Markku, Lakka, Timo A, Lange, Ethan M, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Larson, Eric B, Lee, I-Te, Lehtimaki, Terho, Lewis, Cora E, Li, Huaixing, Li, Jin, Li-Gao, Ruifang, Lin, Honghuang, Lin, Li-An, Lin, Xu, Lind, Lars, Lindstrom, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'an, Lubitz, Steven A, Lyytikainen, Leo-Pekka, Mackey, David A, Madden, Pamela AF, Manning, Alisa K, Mannisto, Satu, Marenne, Gaelle, Marten, Jonathan, Martin, Nicholas G, Mazul, Angela L, Meidtner, Karina, Metspalu, Andres, Mitchell, Paul, Mohlke, Karen L, Mook-Kanamori, Dennis O, Morgan, Anna, Morris, Andrew D, Morris, Andrew P, Mueller-Nurasyid, Martina, Munroe, Patricia B, Nalls, Mike A, Nauck, Matthias, Nelson, Christopher P, Neville, Matt, Nielsen, Sune F, Nikus, Kjell, Njolstad, Pal R, Nordestgaard, Borge G, Ntalla, Ioanna, O'Connel, Jeffrey R, Oksa, Heikki, Loohuis, Loes M Olde, Ophoff, Roel A, Owen, Katharine R, Packard, Chris J, Padmanabhan, Sandosh, Palmer, Colin NA, Pasterkamp, Gerard, Patel, Aniruddh P, Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L, Peloso, Gina M, Pennell, Craig E, Perola, Markus, Perry, James A, Perry, John RB, Person, Thomas N, Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T, Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F, Reiner, Alex P, Renstrom, Frida, Ridker, Paul M, Rioux, John D, Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J, Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K, Schreiner, Pamela J, Schulze, Matthias B, Scott, Robert A, Segura-Lepe, Marcelo P, Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S, Smith, Albert Vernon, Smith, Jennifer A, Southam, Lorraine, Spector, Timothy D, Speliotes, Elizabeth K, Starr, John M, Steinthorsdottir, Valgerdur, Stringham, Heather M, Stumvoll, Michael, Surendran, Praveen, 't Hart, Leen M, Tansey, Katherine E, Tardif, Jean-Claude, Taylor, Kent D, Teumer, Alexander, Thompson, Deborah J, Thorsteinsdottir, Unnur, Thuesen, Betina H, Toenjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg-Hansen, Anne, Tyrer, Jonathan P, Uher, Rudolf, Uitterlinden, Andre G, Ulivi, Sheila, van der Laan, Sander W, Van Der Leij, Andries R, van Duijn, Cornelia M, van Schoor, Natasja M, van Setten, Jessica, Varbo, Anette, Varga, Tibor V, Varma, Rohit, Edwards, Digna R Velez, Vermeulen, Sita H, Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F, Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A, Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J, Warren, Helen R, Wessel, Jennifer, Willems, Sara M, Wilson, James G, Witte, Daniel R, Woods, Michael O, Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges-Armstrong, Laura M, Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I, Boehnke, Michael, Kathiresan, Sekar, McCarthy, Mark I, Willer, Cristen J, Stefansson, Kari, Borecki, Ingrid B, Liu, Dajiang J, North, Kari E, Heard-Costa, Nancy L, Pers, Tune H, Lindgren, Cecilia M, Oxvig, Claus, Kutalik, Zoltan, Rivadeneira, Fernando, Loos, Ruth JF, Frayling, Timothy M, Hirschhorn, Joel N, Deloukas, Panos, Lettre, Guillaume, Consortium, EPIC-InterAct, Consortium, EPIC-CVD, Consortium, CHD Exome, Consortium, ExomeBP, Consortium, T2D-Genes, Consortium, GoT2D Genes, Consortium, Global Lipids Genetics, Consortium, ReproGen, Investigators, MAGIC, Marouli, Eirini, Graff, Mariaelisa, Medina Gomez, Carolina, Lo, Ken Sin, Wood, Andrew R., Kjaer, Troels R., Fine, Rebecca S., Lu, Yingchang, Schurmann, Claudia, Highland, Heather M., Rüeger, Sina, Thorleifsson, Gudmar, Justice, Anne E., Lamparter, David, Stirrups, Kathleen E., Turcot, Valérie, Young, Kristin L., Winkler, Thomas W., Esko, Tõnu, Karaderi, Tugce, Locke, Adam E., Masca, Nicholas G. D., Ng, Maggie C. Y., Mudgal, Poorva, Rivas, Manuel A., Vedantam, Sailaja, Mahajan, Anubha, Guo, Xiuqing, Abecasis, Goncalo, Aben, Katja K., Adair, Linda S., Alam, Dewan S., Albrecht, Eva, Allin, Kristine H., Allison, Matthew, Amouyel, Philippe, Appel, Emil V., Arveiler, Dominique, Asselbergs, Folkert W., Auer, Paul L., Balkau, Beverley, Banas, Bernhard, Bang, Lia E., Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F., Blüher, Matthia, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A., Bonnycastle, Lori L., Bork Jensen, Jette, Bots, Michiel L., Bottinger, Erwin P., Bowden, Donald W., Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H., Broer, Linda, Burt, Amber A., Butterworth, Adam S., Carey, David J., Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Chen, Yii Der Ida, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y., Cocca, Massimiliano, Collins, Francis S., Cook, James P., Corley, Janie, Galbany, Jordi Coromina, Cox, Amanda J., Cuellar Partida, Gabriel, Danesh, John, Davies, Gail, De Bakker, Paul I. W., De Borst, Gert J., De Denus, Simon, De Groot, Mark C. H., De Mutsert, Renée, Deary, Ian J., Dedoussis, George, Demerath, Ellen W., Den Hollander, Anneke I., Dennis, Joe G., Di Angelantonio, Emanuele, Drenos, Fotio, Du, Mengmeng, Dunning, Alison M., Easton, Douglas F., Ebeling, Tapani, Edwards, Todd L., Ellinor, Patrick T., Elliott, Paul, Evangelou, Evangelo, Farmaki, Aliki Eleni, Faul, Jessica D., Feitosa, Mary F., Feng, Shuang, Ferrannini, Ele, Ferrario, Marco M., Ferrieres, Jean, Florez, Jose C., Ford, Ian, Fornage, Myriam, Franks, Paul W., Frikke Schmidt, Ruth, Galesloot, Tessel E., Gan, Wei, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmanta, Giri, Ayush, Girotto, Giorgia, Gordon, Scott D., Gordon Larsen, Penny, Gorski, Mathia, Grarup, Niel, Grove, Megan L., Gudnason, Vilmundur, Gustafsson, Stefan, Hansen, Torben, Harris, Kathleen Mullan, Harris, Tamara B., Hattersley, Andrew T., Hayward, Caroline, He, Liang, Heid, Iris M., Heikkilä, Kauko, Helgeland, Øyvind, Hernesniemi, Jussi, Hewitt, Alex W., Hocking, Lynne J., Hollensted, Mette, Holmen, Oddgeir L., Hovingh, G. Kee, Howson, Joanna M. M., Hoyng, Carel B., Huang, Paul L., Hveem, Kristian, Ikram, M. Arfan, Ingelsson, Erik, Jackson, Anne U., Jansson, Jan Håkan, Jarvik, Gail P., Jensen, Gorm B., Jhun, Min A., Jia, Yucheng, Jiang, Xuejuan, Johansson, Stefan, Jørgensen, Marit E., Jørgensen, Torben, Jousilahti, Pekka, Jukema, J. Wouter, Kahali, Bratati, Kahn, René S., Kähönen, Mika, Kamstrup, Pia R., Kanoni, Stavroula, Kaprio, Jaakko, Karaleftheri, Maria, Kardia, Sharon L. R., Karpe, Fredrik, Kee, Frank, Keeman, Renske, Kiemeney, Lambertus A., Kitajima, Hidetoshi, Kluivers, Kirsten B., Kocher, Thoma, Komulainen, Pirjo, Kontto, Jukka, Kooner, Jaspal S., Kooperberg, Charle, Kovacs, Peter, Kriebel, Jennifer, Kuivaniemi, Helena, Küry, Sébastien, Kuusisto, Johanna, LA BIANCA, Martina, Laakso, Markku, Lakka, Timo A., Lange, Ethan M., Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Larson, Eric B., Lee, I. Te, Lehtimäki, Terho, Lewis, Cora E., Li, Huaixing, Li, Jin, Li Gao, Ruifang, Lin, Honghuang, Lin, Li An, Lin, Xu, Lind, Lar, Lindström, Jaana, Linneberg, Allan, Liu, Yeheng, Liu, Yongmei, Lophatananon, Artitaya, Luan, Jian'An, Lubitz, Steven A., Lyytikäinen, Leo Pekka, Mackey, David A., Madden, Pamela A. F., Manning, Alisa K., Männistö, Satu, Marenne, Gaëlle, Marten, Jonathan, Martin, Nicholas G., Mazul, Angela L., Meidtner, Karina, Metspalu, Andre, Mitchell, Paul, Mohlke, Karen L., Mook Kanamori, Dennis O., Morgan, Anna, Morris, Andrew D., Morris, Andrew P., Müller Nurasyid, Martina, Munroe, Patricia B., Nalls, Mike A., Nauck, Matthia, Nelson, Christopher P., Neville, Matt, Nielsen, Sune F., Nikus, Kjell, Njølstad, Pål R., Nordestgaard, Børge G., Ntalla, Ioanna, O'Connel, Jeffrey R., Oksa, Heikki, Loohuis, Loes M. Olde, Ophoff, Roel A., Owen, Katharine R., Packard, Chris J., Padmanabhan, Sandosh, Palmer, Colin N. A., Pasterkamp, Gerard, Patel, Aniruddh P., Pattie, Alison, Pedersen, Oluf, Peissig, Peggy L., Peloso, Gina M., Pennell, Craig E., Perola, Marku, Perry, James A., Perry, John R. B., Person, Thomas N., Pirie, Ailith, Polasek, Ozren, Posthuma, Danielle, Raitakari, Olli T., Rasheed, Asif, Rauramaa, Rainer, Reilly, Dermot F., Reiner, Alex P., Renström, Frida, Ridker, Paul M., Rioux, John D., Robertson, Neil, Robino, Antonietta, Rolandsson, Olov, Rudan, Igor, Ruth, Katherine S., Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sandow, Kevin, Sapkota, Yadav, Sattar, Naveed, Schmidt, Marjanka K., Schreiner, Pamela J., Schulze, Matthias B., Scott, Robert A., Segura Lepe, Marcelo P., Shah, Svati, Sim, Xueling, Sivapalaratnam, Suthesh, Small, Kerrin S., Smith, Albert Vernon, Smith, Jennifer A., Southam, Lorraine, Spector, Timothy D., Speliotes, Elizabeth K., Starr, John M., Steinthorsdottir, Valgerdur, Stringham, Heather M., Stumvoll, Michael, Surendran, Praveen, Hart'T, Leen M., Tansey, Katherine E., Tardif, Jean Claude, Taylor, Kent D., Teumer, Alexander, Thompson, Deborah J., Thorsteinsdottir, Unnur, Thuesen, Betina H., Tönjes, Anke, Tromp, Gerard, Trompet, Stella, Tsafantakis, Emmanouil, Tuomilehto, Jaakko, Tybjaerg Hansen, Anne, Tyrer, Jonathan P., Uher, Rudolf, Uitterlinden, André G., Ulivi, Sheila, Van Der Laan, Sander W., Van Der Leij, Andries R., Van Duijn, Cornelia M., Van Schoor, Natasja M., Van Setten, Jessica, Varbo, Anette, Varga, Tibor V., Varma, Rohit, Velez Edwards, Digna R., Vermeulen, Sita H., Vestergaard, Henrik, Vitart, Veronique, Vogt, Thomas F., Vozzi, Diego, Walker, Mark, Wang, Feijie, Wang, Carol A., Wang, Shuai, Wang, Yiqin, Wareham, Nicholas J., Warren, Helen R., Wessel, Jennifer, Willems, Sara M., Wilson, James G., Witte, Daniel R., Woods, Michael O., Wu, Ying, Yaghootkar, Hanieh, Yao, Jie, Yao, Pang, Yerges Armstrong, Laura M., Young, Robin, Zeggini, Eleftheria, Zhan, Xiaowei, Zhang, Weihua, Zhao, Jing Hua, Zhao, Wei, Zheng, He, Zhou, Wei, Rotter, Jerome I., Boehnke, Michael, Kathiresan, Sekar, Mccarthy, Mark I., Willer, Cristen J., Stefansson, Kari, Borecki, Ingrid B., Liu, Dajiang J., North, Kari E., Heard Costa, Nancy L., Pers, Tune H., Lindgren, Cecilia M., Oxvig, Clau, Kutalik, Zoltán, Rivadeneira, Fernando, Loos, Ruth J. F., Frayling, Timothy M., Hirschhorn, Joel N., Deloukas, Pano, Lettre, Guillaume, Pharmacoepidemiology and Clinical Pharmacology, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, Internal Medicine, Epidemiology, Obstetrics & Gynecology, Radiology & Nuclear Medicine, Neurology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, British Heart Foundation, Medical Research Council (MRC), Wellcome Trust, National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, Action on Hearing Loss, Home Office, National Institutes of Health, Public Health England, EPIC-InterAct Consortium, CHD Exome+ Consortium, ExomeBP Consortium, T2D-Genes Consortium, GoT2D Genes Consortium, Global Lipids Genetics Consortium, ReproGen Consortium, MAGIC Investigators, Physiology, Human genetics, APH - Personalized Medicine, APH - Aging & Later Life, Epidemiology and Data Science, and Amsterdam Reproduction & Development (AR&D)

Subjects
0301 basic medicine, Male, ReproGen Consortium, Multifactorial Inheritance, Genome-wide association study, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Androgen, ADAMTS Proteins, Gene Frequency, Missing heritability problem, MISSING HERITABILITY, Receptors, 2.1 Biological and endogenous factors, Pregnancy-Associated Plasma Protein-A, Aetiology, Non-U.S. Gov't, Glycosaminoglycans, Genetics, Multidisciplinary, Genome, CHD Exome+ Consortium, Medicine (all), Research Support, Non-U.S. Gov't, T2D-Genes Consortium, Global Lipids Genetics Consortium, Multidisciplinary Sciences, Phenotype, NADPH Oxidase 4, Receptors, Androgen, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Interferon Regulatory Factors, Science & Technology - Other Topics, Intercellular Signaling Peptides and Proteins, Female, Proteoglycans, EPIC-InterAct Consortium, ExomeBP Consortium, Common disease-common variant, Human, Adult, General Science & Technology, Biology, Development, Research Support, Article, GENETIC ARCHITECTURE, N.I.H, 03 medical and health sciences, MAGIC Investigators, Research Support, N.I.H., Extramural, Somatomedins, Genetic variation, MD Multidisciplinary, Journal Article, gene, height, rare, Humans, Hedgehog Proteins, Interleukin-11 Receptor alpha Subunit, Allele, GENOME-WIDE ASSOCIATION, Gene, Allele frequency, Alleles, Genetic association, Genetic association study, Glycoproteins, Science & Technology, MUTATIONS, Genome, Human, ta1184, Human Genome, Extramural, Genetic Variation, NADPH Oxidases, ta3121, Body Height, INTERLEUKIN-11, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], MICE, 030104 developmental biology, GoT2D Genes Consortium, Proteolysis, Procollagen N-Endopeptidase, Cell Adhesion Molecules
Abstract

Contains fulltext : 169801.pdf (Publisher’s version ) (Closed access) Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

Published
2017
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282. Use of Repeated Blood Pressure and Cholesterol Measurements to Improve Cardiovascular Disease Risk Prediction : An Individual-Participant-Data Meta-Analysis

Author

Paige, Ellie, Barrett, Jessica, Pennells, Lisa, Sweeting, Michael, Willeit, Peter, Di Angelantonio, Emanuele, Gudnason, Vilmundur, Nordestgaard, Børge G, Psaty, Bruce M, Goldbourt, Uri, Best, Lyle G, Assmann, Gerd, Salonen, Jukka T, Nietert, Paul J, Verschuren, W M Monique, Brunner, Eric J, Kronmal, Richard A, Salomaa, Veikko, Bakker, Stephan J L, Dagenais, Gilles R, Sato, Shinichi, Jansson, Jan-Håkan, Willeit, Johann, Onat, Altan, de la Cámara, Agustin Gómez, Roussel, Ronan, Völzke, Henry, Dankner, Rachel, Tipping, Robert W, Meade, Tom W, Donfrancesco, Chiara, Kuller, Lewis H, Peters, Annette, Gallacher, John, Kromhout, Daan, Iso, Hiroyasu, Knuiman, Matthew, Casiglia, Edoardo, Kavousi, Maryam, Palmieri, Luigi, Sundström, Johan, Davis, Barry R, Njølstad, Inger, Couper, David, Danesh, John, Thompson, Simon G, Wood, Angela, Clinicum, Department of Public Health, University of Helsinki, Barrett, Jessica [0000-0003-1889-9803], Pennells, Lisa [0000-0002-8594-3061], Sweeting, Michael [0000-0003-0980-8965], Di Angelantonio, Emanuele [0000-0001-8776-6719], Danesh, John [0000-0003-1158-6791], Thompson, Simon [0000-0002-5274-7814], Wood, Angela [0000-0002-7937-304X], Apollo - University of Cambridge Repository, and Epidemiology

Subjects
Adult, MODELS, Blood Pressure, Cholesterol/blood, Risk Assessment, risk prediction, Systematic Reviews, Meta- and Pooled Analyses, SDG 3 - Good Health and Well-being, cardiovascular disease, MULTIPLE, Humans, risk factors, CORONARY-HEART-DISEASE, longitudinal measurements, Cardiac and Cardiovascular Systems, Risk Assessment/methods, repeated measurements, Human Nutrition & Health, Aged, Cardiovascular Disease, Longitudinal Measurements, Repeated Measurements, Risk Factors, Risk Prediction, repeated risk factors, Kardiologi, Cardiovascular Diseases/epidemiology, Humane Voeding & Gezondheid, Blood Pressure Determination, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, 3142 Public health care science, environmental and occupational health, VARIABILITY, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Cholesterol, Cardiovascular Diseases, Female
Abstract

The added value of incorporating information from repeated blood pressure and cholesterol measurements to predict cardiovascular disease (CVD) risk has not been rigorously assessed. We used data on 191,445 adults from the Emerging Risk Factors Collaboration (38 cohorts from 17 countries with data encompassing 1962-2014) with more than 1 million measurements of systolic blood pressure, total cholesterol, and high-density lipoprotein cholesterol. Over a median 12 years of follow-up, 21,170 CVD events occurred. Risk prediction models using cumulative mean values of repeated measurements and summary measures from longitudinal modeling of the repeated measurements were compared with models using measurements from a single time point. Risk discrimination (C-index) and net reclassification were calculated, and changes in C-indices were meta-analyzed across studies. Compared with the single-time-point model, the cumulative means and longitudinal models increased the C-index by 0.0040 (95% confidence interval (CI): 0.0023, 0.0057) and 0.0023 (95% CI: 0.0005, 0.0042), respectively. Reclassification was also improved in both models; compared with the single-time-point model, overall net reclassification improvements were 0.0369 (95% CI: 0.0303, 0.0436) for the cumulative-means model and 0.0177 (95% CI: 0.0110, 0.0243) for the longitudinal model. In conclusion, incorporating repeated measurements of blood pressure and cholesterol into CVD risk prediction models slightly improves risk prediction.

Published
2017
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283. BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis

Author

Evans, Jonathan D. W., Girerd, Barbara, Montani, David, Wang, Xiao Jian, Austin, Eric D., Elliott, Greg, Asano, Koichiro, Grünig, Ekkehard, Yan, Yi, Jing, Zhi Cheng, Wheeler, Lisa A., Nakayama, Ikue, Satoh, Toru, Eichstaedt, Christina, Hinderhofer, Katrin, Wolf, Matthias, Rosenzweig, Erika B., Chung, Wendy K., Soubrier, Florent, Simonneau, Gérald, Sitbon, Olivier, Gräf, Stefan, Kaptoge, Stephen, Di Angelantonio, Emanuele, Humbert, Marc, Morrell, Nicholas W., GALIE', NAZZARENO, MANES, ALESSANDRA, PALAZZINI, MASSIMILIANO, Graf, Stefan [0000-0002-1315-8873], Kaptoge, Stephen [0000-0002-1155-4872], Di Angelantonio, Emanuele [0000-0001-8776-6719], Morrell, Nicholas [0000-0001-5700-9792], Apollo - University of Cambridge Repository, Evans, Jonathan D.W., Girerd, Barbara, Montani, David, Wang, Xiao-Jian, Galiè, Nazzareno, Austin, Eric D., Elliott, Greg, Asano, Koichiro, Grünig, Ekkehard, Yan, Yi, Jing, Zhi-Cheng, Manes, Alessandra, Palazzini, Massimiliano, Wheeler, Lisa A., Nakayama, Ikue, Satoh, Toru, Eichstaedt, Christina, Hinderhofer, Katrin, Wolf, Matthia, Rosenzweig, Erika B., Chung, Wendy K., Soubrier, Florent, Simonneau, Gérald, Sitbon, Olivier, Gräf, Stefan, Kaptoge, Stephen, Di Angelantonio, Emanuele, Humbert, Marc, and Morrell, Nicholas W

Subjects
Adult, Male, Pulmonary hypertension, geneticas, Hypertension, Pulmonary, Articles, Middle Aged, Bone Morphogenetic Protein Receptors, Type II, Prognosis, Survival Rate, Young Adult, Mutation, Humans, Familial Primary Pulmonary Hypertension, Female, Lung Transplantation, Proportional Hazards Models
Abstract

BACKGROUND: Mutations in the gene encoding the bone morphogenetic protein receptor type II (BMPR2) are the commonest genetic cause of pulmonary arterial hypertension (PAH). However, the effect of BMPR2 mutations on clinical phenotype and outcomes remains uncertain. METHODS: We analysed individual participant data of 1550 patients with idiopathic, heritable, and anorexigen-associated PAH from eight cohorts that had been systematically tested for BMPR2 mutations. The primary outcome was the composite of death or lung transplantation. All-cause mortality was the secondary outcome. Hazard ratios (HRs) for death or transplantation and all-cause mortality associated with the presence of BMPR2 mutation were calculated using Cox proportional hazards models stratified by cohort. FINDINGS: Overall, 448 (29%) of 1550 patients had a BMPR2 mutation. Mutation carriers were younger at diagnosis (mean age 35·4 [SD 14·8] vs 42·0 [17·8] years), had a higher mean pulmonary artery pressure (60·5 [13·8] vs 56·4 [15·3] mm Hg) and pulmonary vascular resistance (16·6 [8·3] vs 12·9 [8·3] Wood units), and lower cardiac index (2·11 [0·69] vs 2·51 [0·92] L/min per m(2); all p

Published
2015

284. Associations of cardiovascular risk factors with venous thromboembolism

Author

Gregson, John, Kaptoge, Stephen K., Bolton, Thomas, Pennells, L., Williet, Peter, Burgess, Stephen, Bell, Steven, Sweeting, Michael, Rimm, Eric B., Kabrhel, Christopher, Zoller, Bengt, Assmann, Gerd, Gudnason, Vilmundur, Folsom, Aaron R., Arndt, Volker, Fletcher, Astrid, Norman, Paul E., Nordestgaard, Børge G., Kitamura, Akihiko, Mahmoodi, Bakhtawar K., Whincup, Peter H, Knuiman, Matthew, Salomaa, Veikko, Meisinger, Christa, Koenig, Wolfgang, Kavousi, Maryam, Cooper, Cyrus, Völzke, Henry, Cooper, Jackie A., Ninomiya, Toshiharu, Casiglia, Edoardo, Rodriguez-Labajos, Beatriz, Ben-Shlomo, Yoav Ben, Despres, Jean-Pierre, Sinons, Leon, Barrett-Connor, Elizabeth, Bjorkelund, Cecilia, Notdurfter, Marlene, Kromhout, Daan, Price, Jackie, Sutherland, Susan E., Sundstrom, Johan, Kauhanen, Jussi, Gallacher, John, Beulens, Joline W.J., Dankner, Rachel, Giampaoli, Simona, Deen, Jason F., Gomez de la Camara, Agustin, Kuller, Lewis H., Rosengren, Annika, Svensson, Peter J., Nagel, Dorothea, Crespo, Carlos J., Brenner, Hermann, Albertorio-Diaz, Juan R., Atkins, Robert, Brunner, Eric J., Shipley, Martin, Njorstad, Inger, Lawlor, Deborah A., van der Schouw, Y. T., Selmer, R., Trevisan, Morena, Verschuren, W. M. M., Greenland, Philip, Wasserthell-Smoller, Sylvia, Lowe, Gordon D.O., Wood, Angela M., Butterworth, Adam S., Thompson, Simon, Danesh, John, Di Angelantonio, Emanuele, and Meade, Tom

Published
2018

285. Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program

Author

Klarin, Derek, Damrauer, Scott M, Cho, Kelly, Sun, Yan V, Teslovich, Tanya M, Honerlaw, Jacqueline, Gagnon, David R, DuVall, Scott L, Li, Jin, Peloso, Gina M, Chaffin, Mark, Small, Aeron M, Huang, Jie, Tang, Hua, Lynch, Julie A, Ho, Yuk-Lam, Liu, Dajiang J, Emdin, Connor A, Li, Alexander H, Huffman, Jennifer E, Lee, Jennifer S, Natarajan, Pradeep, Chowdhury, Rajiv, Saleheen, Danish, Vujkovic, Marijana, Baras, Aris, Pyarajan, Saiju, Di Angelantonio, Emanuele, Neale, Benjamin M, Naheed, Aliya, Khera, Amit V, Danesh, John, Chang, Kyong-Mi, Abecasis, Gonçalo, Willer, Cristen, Dewey, Frederick E, Carey, David J, Global Lipids Genetics Consortium, Myocardial Infarction Genetics (MIGen) Consortium, Geisinger-Regeneron DiscovEHR Collaboration, VA Million Veteran Program, Concato, John, Gaziano, J Michael, O'Donnell, Christopher J, Tsao, Philip S, Kathiresan, Sekar, Rader, Daniel J, Wilson, Peter WF, Assimes, Themistocles L, Gagnon, David R [0000-0002-6367-3179], Chaffin, Mark [0000-0002-1234-5562], Emdin, Connor A [0000-0002-2385-8259], Huffman, Jennifer E [0000-0002-9672-2491], Vujkovic, Marijana [0000-0003-4924-5714], Neale, Benjamin M [0000-0003-1513-6077], Willer, Cristen [0000-0001-5645-4966], Kathiresan, Sekar [0000-0002-6724-032X], Assimes, Themistocles L [0000-0003-2349-0009], and Apollo - University of Cambridge Repository

Subjects
Male, Genotype, Black People, Hispanic or Latino, Middle Aged, Lipid Metabolism, Lipids, Polymorphism, Single Nucleotide, White People, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Ethnicity, Humans, Female, Aged, Genome-Wide Association Study, Veterans
Abstract

The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).

Published
2018

286. Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies

Author

Burgess, Stephen, Ference, Brian A., Staley, James R., Freitag, Daniel F., Mason, Amy M., Nielsen, Sune F., Willeit, Peter, Young, Robin, Surendran, Praveen, Karthikeyan, Savita, Bolton, Thomas R., Peters, James E., Kamstrup, Pia R., Tybjærg-Hansen, Anne, Benn, Marianne, Langsted, Anne, Schnohr, Peter, Vedel-Krogh, Signe, Kobylecki, Camilla J., Ford, Ian, Packard, Chris, Trompet, Stella, Jukema, J. Wouter, Sattar, Naveed, Di Angelantonio, Emanuele, Saleheen, Danish, Howson, Joanna M. M., Nordestgaard, Børge G., Butterworth, Adam S., Danesh, John, Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom, MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark, The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark, Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom, Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom, Department of Cardiology, Leiden University Medical Centre, Leiden, the Netherlands, and Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia

Published
2018

287. Automated Typing of Red Blood Cell and Platelet Antigens from Whole Genome Sequencing

Author

Lane, William J., Westhoff, Connie M., Gleadall, Nicholas S., Aguad, Maria, Smeland-Wagman, Robin, Vege, Sunitha, Simmons, Daimon P., Mah, Helen H., Lebo, Matthew S., Walter, Klaudia, Soranzo, Nicole, Angelantonio, Emanuele Di, Danesh, John, Roberts, David J., Watkins, Nick A., Ouwehand, Willem H., Butterworth, Adam S., Kaufman, Richard M., Rehm, Heidi L., Silberstein, Leslie E., and Green, Robert C.

Subjects
Adult, Aged, 80 and over, Blood Platelets, Erythrocytes, Rh-Hr Blood-Group System, Adolescent, Whole Genome Sequencing, Genome, Human, Middle Aged, Article, ABO Blood-Group System, Young Adult, Blood Grouping and Crossmatching, Databases, Genetic, Humans, Antigens, Human Platelet, Algorithms, Aged, Randomized Controlled Trials as Topic
Abstract

BACKGROUND: There are over 300 known red blood cell (RBC) antigens and 33 platelet (PLT) antigens that differ between individuals. Sensitization to antigens is a serious complication in prenatal medicine and following blood transfusion, especially for patients requiring multiple transfusions. Although current pre-transfusion compatibility testing largely relies on serologic methods, reagents are not available for many antigens. DNA-based single nucleotide polymorphisms (SNP) array methods have been applied, but typing for ABO and Rh, the most important blood groups, cannot be done by SNP typing alone. New methods are needed for RBC and PLT antigen determination. METHODS: The MedSeq Project was a randomized clinical trial designed to examine the integration of wide-ranging genomic information into the practice of medicine. Subjects were enrolled by participating physicians during visits for primary care for generally healthy adults and subspecialty care for patients with cardiomyopathy. All participants underwent a standardized family history assessment after which they were block-randomized into either the whole genome sequencing (WGS) arm or the no sequencing arm. The primary endpoint of the overall MedSeq Project was to study the effect of adding WGS to medical care. This study has been completed and is registered with ClinicalTrials.gov, number NCT01736566. The WGS based RBC and PLT antigen typing presented here is a substudy of the WGS arm with no measured patient outcomes (n=110). A curated database of RBC and PLT antigen molecular changes was created (http://bloodantigens.com), followed by the development of an automated WGS-based antigen typing algorithm (bloodTyper). WGS data from 110 MedSeq participants (30x depth) were used to evaluate bloodTyper against conventional serology and SNP typing for 38 RBC antigens in 12 blood group systems (17 serology and 35 SNP) and 22 PLT antigens (22 SNP). Additional validation was performed using WGS data from 200 INTERVAL participants (15x depth) with serologic comparison (21 RBC antigens). FINDINGS: The WGS typing algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. The initial WGS typing algorithm was 99.5% concordant over the first 20 MedSeq genomes. Addressing the discordances led to the development of an improved algorithm which was 99.8% concordant for the remaining 90 MedSeq genomes. Additional, modifications led to the final algorithm which was 99.2% concordant over 200 INTERVAL genomes (or 99.9% after adjustment for the lower depth of coverage). INTERPRETATION: By enabling more precise antigen-matching of patients with blood donors, WGS-based antigen typing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine. FUNDING: National Human Genome Research Institute, Doris Duke Charitable Foundation, and NHS Blood and Transplant, National Institute for Health Research, and Wellcome Trust.

Published
2018

288. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas GD, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie CY, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Gonçalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der I, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul IW, Groot, Mark CH, Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, Heijer, Martin, Hollander, Anneke I, Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, and Easton, Douglas F

Subjects
INTERVAL Study, ReproGen Consortium, Understanding Society Scientific Group, CHD Exome+ Consortium, T2D-Genes Consortium, Biological Sciences, Medical and Health Sciences, EPIC-CVD Consortium, MAGIC Investigators, GoT2D Genes Consortium, Global Lipids Genetic Consortium, EPIC InterAct Consortium, Obesity, ExomeBP Consortium, Nutrition, Developmental Biology
Abstract

In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.

Published
2018

289. High-Sensitivity Cardiac Troponin and New-Onset Heart Failure: A Systematic Review and Meta-Analysis of 67,063 Patients With 4,165 Incident Heart Failure Events

Author

Evans, Jonathan DW, Dobbin, Stephen JH, Pettit, Stephen J, Di Angelantonio, Emanuele, and Willeit, Peter

Subjects
meta-analysis, Heart Failure, Male, risk prediction, Myocardial Infarction, biomarkers, Humans, Female, Middle Aged, Troponin, Aged
Abstract

OBJECTIVES: The aim of this study was to systematically collate and appraise the available evidence regarding the association between high-sensitivity cardiac troponin (hs-cTn) and incident heart failure (HF) and the added value of hs-cTn in HF prediction. BACKGROUND: Identification of subjects at high risk for HF and early risk factor modification with medications such as angiotensin-converting enzyme inhibitors may delay the onset of HF. Hs-cTn has been suggested as a prognostic marker for the incidence of first-ever HF in asymptomatic subjects. METHODS: PubMed, Embase, and Web of Science were systematically searched for prospective cohort studies published before January 2017 that reported associations between hs-cTn and incident HF in subjects without baseline HF. Study-specific multivariate-adjusted hazard ratios (HRs) were pooled using random-effects meta-analysis. RESULTS: Data were collated from 16 studies with a total of 67,063 subjects and 4,165 incident HF events. The average age was 57 years, and 47% were women. Study quality was high (Newcastle-Ottawa score 8.2 of 9). In a comparison of participants in the top third with those in the bottom third of baseline values of hs-cTn, the pooled multivariate-adjusted HR for incident HF was 2.09 (95% confidence interval [CI]: 1.76 to 2.48; p < 0.001). Between-study heterogeneity was high, with an I2 value of 80%. HRs were similar in men and women (2.29 [95% CI: 1.64 to 3.21] vs. 2.18 [95% CI: 1.68 to 2.81]) and for hs-cTnI and hs-cTnT (2.09 [95% CI: 1.53 to 2.85] vs. 2.11 [95% CI: 1.69 to 2.63]) and across other study-level characteristics. Further adjustment for B-type natriuretic peptide yielded a similar HR of 2.08 (95% CI: 1.64 to 2.65). Assay of hs-cTn in addition to conventional risk factors provided improvements in the C index of 1% to 3%. CONCLUSIONS: Available prospective studies indicate a strong association of hs-cTn with the risk of first-ever HF and significant improvements in HF prediction.

Published
2018
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290. Genomic risk prediction of coronary artery disease in nearly 500,000 adults: implications for early screening and primary prevention

Author

Inouye, Michael, Abraham, Gad, Nelson, Christopher, Wood, Angela, Sweeting, Michael, Dudbridge, Frank, Lai, Florence, Kaptoge, Stephen, Brozynska, Marta, Wang, Tingting, Ye, Shu, Webb, Thomas, Rutter, Martin, Tzoulaki, Ioanna, Patel, Riyaz, Loos, Ruth JF, Keavney, Bernard, Hemingway, Harry, Thompson, John, Watkins, Hugh, Deloukas, Panos, Angelantonio, Emanuele Di, Butterworth, Adam, Danesh, John, Samani, Nilesh, for The UK Biobank CardioMetabolic Consortium CHD Working Group, Inouye, Michael [0000-0001-9413-6520], Nelson, Christopher [0000-0001-8025-2897], Sweeting, Michael [0000-0003-0980-8965], Dudbridge, Frank [0000-0002-8817-8908], Rutter, Martin [0000-0001-6380-539X], Hemingway, Harry [0000-0003-2279-0624], Samani, Nilesh [0000-0002-3286-8133], and Apollo - University of Cambridge Repository

Subjects
for The UK Biobank CardioMetabolic Consortium CHD Working Group
Abstract

Background Coronary artery disease (CAD) has substantial heritability and a polygenic architecture; however, genomic risk scores have not yet leveraged the totality of genetic information available nor been externally tested at population-scale to show potential utility in primary prevention. Methods Using a meta-analytic approach to combine large-scale genome-wide and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS), consisting of 1.7 million genetic variants. We externally tested metaGRS, individually and in combination with available conventional risk factors, in 22,242 CAD cases and 460,387 non-cases from UK Biobank. Findings In UK Biobank, a standard deviation increase in metaGRS had a hazard ratio (HR) of 1.71 (95% CI 1.68–1.73) for CAD, greater than any other externally tested genetic risk score. Individuals in the top 20% of the metaGRS distribution had a HR of 4.17 (95% CI 3.97–4.38) compared with those in the bottom 20%. The metaGRS had higher C-index (C=0.623, 95% CI 0.615–0.631) for incident CAD than any of four conventional factors (smoking, diabetes, hypertension, and body mass index), and addition of the metaGRS to a model of conventional risk factors increased C-index by 3.7%. In individuals on lipid-lowering or anti-hypertensive medications at recruitment, metaGRS hazard for incident CAD was significantly but only partially attenuated with HR of 2.83 (95% CI 2.61– 3.07) between the top and bottom 20% of the metaGRS distribution. Interpretation Recent genetic association studies have yielded enough information to meaningfully stratify individuals using the metaGRS for CAD risk in both early and later life, thus enabling targeted primary intervention in combination with conventional risk factors. The metaGRS effect was partially attenuated by lipid and blood pressure-lowering medication, however other prevention strategies will be required to fully benefit from earlier genomic risk stratification. Funding National Health and Medical Research Council of Australia, British Heart Foundation, Australian Heart Foundation.

Published
2018

291. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Turcot, Valérie, Lu, Yingchang, Highland, Heather M, Schurmann, Claudia, Justice, Anne E, Fine, Rebecca S, Bradfield, Jonathan P, Esko, Tõnu, Giri, Ayush, Graff, Mariaelisa, Guo, Xiuqing, Hendricks, Audrey E, Karaderi, Tugce, Lempradl, Adelheid, Locke, Adam E, Mahajan, Anubha, Marouli, Eirini, Sivapalaratnam, Suthesh, Young, Kristin L, Alfred, Tamuno, Feitosa, Mary F, Masca, Nicholas GD, Manning, Alisa K, Medina-Gomez, Carolina, Mudgal, Poorva, Ng, Maggie CY, Reiner, Alex P, Vedantam, Sailaja, Willems, Sara M, Winkler, Thomas W, Abecasis, Gonçalo, Aben, Katja K, Alam, Dewan S, Alharthi, Sameer E, Allison, Matthew, Amouyel, Philippe, Asselbergs, Folkert W, Auer, Paul L, Balkau, Beverley, Bang, Lia E, Barroso, Inês, Bastarache, Lisa, Benn, Marianne, Bergmann, Sven, Bielak, Lawrence F, Blüher, Matthias, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Böger, Carsten A, Bork-Jensen, Jette, Bots, Michiel L, Bottinger, Erwin P, Bowden, Donald W, Brandslund, Ivan, Breen, Gerome, Brilliant, Murray H, Broer, Linda, Brumat, Marco, Burt, Amber A, Butterworth, Adam S, Campbell, Peter T, Cappellani, Stefania, Carey, David J, Catamo, Eulalia, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Chen, Yii-Der I, Chowdhury, Rajiv, Christensen, Cramer, Chu, Audrey Y, Cocca, Massimiliano, Collins, Francis S, Cook, James P, Corley, Janie, Corominas Galbany, Jordi, Cox, Amanda J, Crosslin, David S, Cuellar-Partida, Gabriel, D'Eustacchio, Angela, Danesh, John, Davies, Gail, Bakker, Paul IW, Groot, Mark CH, Mutsert, Renée, Deary, Ian J, Dedoussis, George, Demerath, Ellen W, Heijer, Martin, Hollander, Anneke I, Ruijter, Hester M, Dennis, Joe G, Denny, Josh C, Di Angelantonio, Emanuele, Drenos, Fotios, Du, Mengmeng, Dubé, Marie-Pierre, Dunning, Alison M, and Easton, Douglas F

Subjects
INTERVAL Study, Adult, Male, ReproGen Consortium, Understanding Society Scientific Group, Cardiovascular, Medical and Health Sciences, EPIC-CVD Consortium, Oral and gastrointestinal, Body Mass Index, MAGIC Investigators, Gene Frequency, Genetics, Animals, Humans, 2.1 Biological and endogenous factors, Global Lipids Genetic Consortium, Obesity, Aetiology, Metabolic and endocrine, Nutrition, Cancer, CHD Exome+ Consortium, Human Genome, Proteins, Genetic Variation, T2D-Genes Consortium, Syndrome, Biological Sciences, Stroke, GoT2D Genes Consortium, Drosophila, Female, EPIC InterAct Consortium, ExomeBP Consortium, Energy Metabolism, Energy Intake, Biotechnology, Developmental Biology
Abstract

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observedto be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMIconfirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

Published
2018

292. Lipoprotein signatures of cholesteryl ester transfer protein and HMG-CoA reductase inhibition

Author

Kettunen, Johannes, primary, Holmes, Michael V., additional, Allara, Elias, additional, Anufrieva, Olga, additional, Ohukainen, Pauli, additional, Oliver-Williams, Clare, additional, Wang, Qin, additional, Tillin, Therese, additional, Hughes, Alun D., additional, Kähönen, Mika, additional, Lehtimäki, Terho, additional, Viikari, Jorma, additional, Raitakari, Olli T., additional, Salomaa, Veikko, additional, Järvelin, Marjo-Riitta, additional, Perola, Markus, additional, Davey Smith, George, additional, Chaturvedi, Nish, additional, Danesh, John, additional, Di Angelantonio, Emanuele, additional, Butterworth, Adam S., additional, and Ala-Korpela, Mika, additional

Published
2019
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293. Integrative analysis of the plasma proteome and polygenic risk of cardiometabolic diseases

Author

Ritchie, Scott C., primary, Lambert, Samuel A., additional, Arnold, Matthew, additional, Teo, Shu Mei, additional, Lim, Sol, additional, Scepanovic, Petar, additional, Marten, Jonathan, additional, Zahid, Sohail, additional, Chaffin, Mark, additional, Liu, Yingying, additional, Abraham, Gad, additional, Ouwehand, Willem H., additional, Roberts, David J., additional, Watkins, Nicholas A., additional, Drew, Brian G., additional, Calkin, Anna C., additional, Di Angelantonio, Emanuele, additional, Soranzo, Nicole, additional, Burgess, Stephen, additional, Chapman, Michael, additional, Kathiresan, Sekar, additional, Khera, Amit V., additional, Danesh, John, additional, Butterworth, Adam S., additional, and Inouye, Michael, additional

Published
2019
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294. Genome-wide analysis identifies molecular systems and 149 genetic loci associated with income

Author

Hill, W. David, primary, Davies, Neil M., additional, Ritchie, Stuart J., additional, Skene, Nathan G., additional, Bryois, Julien, additional, Bell, Steven, additional, Di Angelantonio, Emanuele, additional, Roberts, David J., additional, Xueyi, Shen, additional, Davies, Gail, additional, Liewald, David C. M., additional, Porteous, David J., additional, Hayward, Caroline, additional, Butterworth, Adam S., additional, McIntosh, Andrew M., additional, Gale, Catharine R., additional, and Deary, Ian J., additional

Published
2019
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296. World Health Organization cardiovascular disease risk charts: revised models to estimate risk in 21 global regions

Author

Kaptoge, Stephen, primary, Pennells, Lisa, additional, De Bacquer, Dirk, additional, Cooney, Marie Therese, additional, Kavousi, Maryam, additional, Stevens, Gretchen, additional, Riley, Leanne Margaret, additional, Savin, Stefan, additional, Khan, Taskeen, additional, Altay, Servet, additional, Amouyel, Philippe, additional, Assmann, Gerd, additional, Bell, Steven, additional, Ben-Shlomo, Yoav, additional, Berkman, Lisa, additional, Beulens, Joline W, additional, Björkelund, Cecilia, additional, Blaha, Michael, additional, Blazer, Dan G, additional, Bolton, Thomas, additional, Bonita Beaglehole, Ruth, additional, Brenner, Hermann, additional, Brunner, Eric J, additional, Casiglia, Edoardo, additional, Chamnan, Parinya, additional, Choi, Yeun-Hyang, additional, Chowdry, Rajiv, additional, Coady, Sean, additional, Crespo, Carlos J, additional, Cushman, Mary, additional, Dagenais, Gilles R, additional, D'Agostino Sr, Ralph B, additional, Daimon, Makoto, additional, Davidson, Karina W, additional, Engström, Gunnar, additional, Ford, Ian, additional, Gallacher, John, additional, Gansevoort, Ron T, additional, Gaziano, Thomas Andrew, additional, Giampaoli, Simona, additional, Grandits, Greg, additional, Grimsgaard, Sameline, additional, Grobbee, Diederick E, additional, Gudnason, Vilmundur, additional, Guo, Qi, additional, Tolonen, Hanna, additional, Humphries, Steve, additional, Iso, Hiroyasu, additional, Jukema, J Wouter, additional, Kauhanen, Jussi, additional, Kengne, Andre Pascal, additional, Khalili, Davood, additional, Koenig, Wolfgang, additional, Kromhout, Daan, additional, Krumholz, Harlan, additional, Lam, TH, additional, Laughlin, Gail, additional, Marín Ibañez, Alejandro, additional, Meade, Tom W, additional, Moons, Karel G M, additional, Nietert, Paul J, additional, Ninomiya, Toshiharu, additional, Nordestgaard, Børge G, additional, O'Donnell, Christopher, additional, Palmieri, Luigi, additional, Patel, Anushka, additional, Perel, Pablo, additional, Price, Jackie F, additional, Providencia, Rui, additional, Ridker, Paul M, additional, Rodriguez, Beatriz, additional, Rosengren, Annika, additional, Roussel, Ronan, additional, Sakurai, Masaru, additional, Salomaa, Veikko, additional, Sato, Shinichi, additional, Schöttker, Ben, additional, Shara, Nawar, additional, Shaw, Jonathan E, additional, Shin, Hee-Choon, additional, Simons, Leon A, additional, Sofianopoulou, Eleni, additional, Sundström, Johan, additional, Völzke, Henry, additional, Wallace, Robert B, additional, Wareham, Nicholas J, additional, Willeit, Peter, additional, Wood, David, additional, Wood, Angela, additional, Zhao, Dong, additional, Woodward, Mark, additional, Danaei, Goodarz, additional, Roth, Gregory, additional, Mendis, Shanthi, additional, Onuma, Oyere, additional, Varghese, Cherian, additional, Ezzati, Majid, additional, Graham, Ian, additional, Jackson, Rod, additional, Danesh, John, additional, and Di Angelantonio, Emanuele, additional

Published
2019
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297. Use of polygenic risk scores and other molecular markers to enhance cardiovascular risk prediction: prospective cohort study and modelling analysis

Author

Sun, Luanluan, primary, Pennells, Lisa, additional, Kaptoge, Stephen, additional, Nelson, Christopher P, additional, Abraham, Gad, additional, Arnold, Matthew, additional, Bell, Steven, additional, Bolton, Thomas, additional, Burgess, Stephen, additional, Dudbridge, Frank, additional, Guo, Qi, additional, Ritchie, Scott C, additional, Sofianopoulou, Eleni, additional, Stevens, David, additional, Thompson, John R, additional, Butterworth, Adam S, additional, Wood, Angela, additional, Danesh, John, additional, Samani, Nilesh J, additional, Inouye, Michael, additional, and Angelantonio, Emanuele Di, additional

Published
2019
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298. Genetic determinants of lipids and cardiovascular disease outcomes: a wide-angled Mendelian randomization investigation

Author

Allara, Elias, primary, Morani, Gabriele, additional, Carter, Paul, additional, Gkatzionis, Apostolos, additional, Zuber, Verena, additional, Foley, Christopher N, additional, Rees, Jessica MB, additional, Mason, Amy M, additional, Bell, Steven, additional, Gill, Dipender, additional, Butterworth, Adam S, additional, Angelantonio, Emanuele Di, additional, Peters, James, additional, and Burgess, Stephen, additional

Published
2019
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300. Effect of communicating phenotypic and genetic risk of coronary heart disease alongside web-based lifestyle advice: the INFORM Randomised Controlled Trial

Author

Silarova, Barbora, primary, Sharp, Stephen, additional, Usher-Smith, Juliet A, additional, Lucas, Joanne, additional, Payne, Rupert A, additional, Shefer, Guy, additional, Moore, Carmel, additional, Girling, Christine, additional, Lawrence, Kathryn, additional, Tolkien, Zoe, additional, Walker, Matthew, additional, Butterworth, Adam, additional, Di Angelantonio, Emanuele, additional, Danesh, John, additional, and Griffin, Simon J, additional

Published
2019
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