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2. Risk of cardiovascular events after an exacerbation of chronic obstructive pulmonary disease: results from the EXACOS-CV cohort study using the PHARMO Data Network in the Netherlands

Author

Swart, Karin M. A., Baak, Brenda N., Lemmens, Louise, Penning-van Beest, Fernie J. A., Bengtsson, Camilla, Lobier, Muriel, Hoti, Fabian, Vojinovic, Dina, van Burk, Lindy, Rhodes, Kirsty, Garbe, Edeltraut, Herings, Ron M. C., Nordon, Clementine, and Simons, Sami O.

Published
2023
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3. A meta-analysis of previous falls and subsequent fracture risk in cohort studies

Author

Vandenput, Liesbeth, Johansson, Helena, McCloskey, Eugene V., Liu, Enwu, Schini, Marian, Åkesson, Kristina E., Anderson, Fred A., Azagra, Rafael, Bager, Cecilie L., Beaudart, Charlotte, Bischoff-Ferrari, Heike A., Biver, Emmanuel, Bruyère, Olivier, Cauley, Jane A., Center, Jacqueline R., Chapurlat, Roland, Christiansen, Claus, Cooper, Cyrus, Crandall, Carolyn J., Cummings, Steven R., da Silva, José A. P., Dawson-Hughes, Bess, Diez-Perez, Adolfo, Dufour, Alyssa B., Eisman, John A., Elders, Petra J. M., Ferrari, Serge, Fujita, Yuki, Fujiwara, Saeko, Glüer, Claus-Christian, Goldshtein, Inbal, Goltzman, David, Gudnason, Vilmundur, Hall, Jill, Hans, Didier, Hoff, Mari, Hollick, Rosemary J., Huisman, Martijn, Iki, Masayuki, Ish-Shalom, Sophia, Jones, Graeme, Karlsson, Magnus K., Khosla, Sundeep, Kiel, Douglas P., Koh, Woon-Puay, Koromani, Fjorda, Kotowicz, Mark A., Kröger, Heikki, Kwok, Timothy, Lamy, Olivier, Langhammer, Arnulf, Larijani, Bagher, Lippuner, Kurt, McGuigan, Fiona E. A., Mellstrom, Dan, Merlijn, Thomas, Nguyen, Tuan V., Nordström, Anna, Nordström, Peter, O'Neill, Terence W., Obermayer-Pietsch, Barbara, Ohlsson, Claes, Orwoll, Eric S., Pasco, Julie A., Rivadeneira, Fernando, Schott, Anne-Marie, Shiroma, Eric J., Siggeirsdottir, Kristin, Simonsick, Eleanor M., Sornay-Rendu, Elisabeth, Sund, Reijo, Swart, Karin M. A., Szulc, Pawel, Tamaki, Junko, Torgerson, David J., van Schoor, Natasja M., van Staa, Tjeerd P., Vila, Joan, Wareham, Nicholas J., Wright, Nicole C., Yoshimura, Noriko, Zillikens, MCarola, Zwart, Marta, Harvey, Nicholas C., Lorentzon, Mattias, Leslie, William D., Kanis, John A., Vandenput, Liesbeth, Johansson, Helena, McCloskey, Eugene V., Liu, Enwu, Schini, Marian, Åkesson, Kristina E., Anderson, Fred A., Azagra, Rafael, Bager, Cecilie L., Beaudart, Charlotte, Bischoff-Ferrari, Heike A., Biver, Emmanuel, Bruyère, Olivier, Cauley, Jane A., Center, Jacqueline R., Chapurlat, Roland, Christiansen, Claus, Cooper, Cyrus, Crandall, Carolyn J., Cummings, Steven R., da Silva, José A. P., Dawson-Hughes, Bess, Diez-Perez, Adolfo, Dufour, Alyssa B., Eisman, John A., Elders, Petra J. M., Ferrari, Serge, Fujita, Yuki, Fujiwara, Saeko, Glüer, Claus-Christian, Goldshtein, Inbal, Goltzman, David, Gudnason, Vilmundur, Hall, Jill, Hans, Didier, Hoff, Mari, Hollick, Rosemary J., Huisman, Martijn, Iki, Masayuki, Ish-Shalom, Sophia, Jones, Graeme, Karlsson, Magnus K., Khosla, Sundeep, Kiel, Douglas P., Koh, Woon-Puay, Koromani, Fjorda, Kotowicz, Mark A., Kröger, Heikki, Kwok, Timothy, Lamy, Olivier, Langhammer, Arnulf, Larijani, Bagher, Lippuner, Kurt, McGuigan, Fiona E. A., Mellstrom, Dan, Merlijn, Thomas, Nguyen, Tuan V., Nordström, Anna, Nordström, Peter, O'Neill, Terence W., Obermayer-Pietsch, Barbara, Ohlsson, Claes, Orwoll, Eric S., Pasco, Julie A., Rivadeneira, Fernando, Schott, Anne-Marie, Shiroma, Eric J., Siggeirsdottir, Kristin, Simonsick, Eleanor M., Sornay-Rendu, Elisabeth, Sund, Reijo, Swart, Karin M. A., Szulc, Pawel, Tamaki, Junko, Torgerson, David J., van Schoor, Natasja M., van Staa, Tjeerd P., Vila, Joan, Wareham, Nicholas J., Wright, Nicole C., Yoshimura, Noriko, Zillikens, MCarola, Zwart, Marta, Harvey, Nicholas C., Lorentzon, Mattias, Leslie, William D., and Kanis, John A.

Abstract

Summary The relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm. Introduction Previous falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD). Methods The resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients. Results Falls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95

Published
2024
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4. Challenges and lessons learned from a long-term postauthorisation safety study programme of rivaroxaban in Europe

Author

Brobert, Gunnar, primary, Ruigomez, Ana, additional, Schink, Tania, additional, Voss, Annemarie, additional, Herings, Ron, additional, Smits, Elisabeth, additional, Swart, Karin M A, additional, Friberg, Leif, additional, Balabanova, Yanina, additional, Tarenz, Christine, additional, Suzart-Woischnik, Kiliana, additional, Soriano-Gabarró, Montse, additional, Vora, Pareen, additional, Homering, Martin, additional, Dyszynski, Tomasz, additional, Nagel, Gerd, additional, Amaya, Pablo, additional, and García Rodríguez, Luis Alberto, additional

Published
2024
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5. Disentangling the genetics of lean mass

Author

Karasik, David, Zillikens, M Carola, Hsu, Yi-Hsiang, Aghdassi, Ali, Akesson, Kristina, Amin, Najaf, Barroso, Inês, Bennett, David A, Bertram, Lars, Bochud, Murielle, Borecki, Ingrid B, Broer, Linda, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos-Obando, Natalia, Cauley, Jane A, Cawthon, Peggy M, Chambers, John C, Chen, Zhao, Cho, Nam H, Choi, Hyung Jin, Chou, Wen-Chi, Cummings, Steven R, de Groot, Lisette C P G M, De Jager, Phillip L, Demuth, Ilja, Diatchenko, Luda, Econs, Michael J, Eiriksdottir, Gudny, Enneman, Anke W, Eriksson, Joel, Eriksson, Johan G, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Gieger, Christian, Grallert, Harald, Gudnason, Vilmundur, Lenore, Launer J, Hayward, Caroline, Hofman, Albert, Homuth, Georg, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Johnson, Toby, Biffar, Reiner, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline S L, Koller, Daniel L, Kooner, Jaspal S, Kraus, William E, Kritchevsky, Stephen, Kutalik, Zoltán, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Lerch, Markus M, Lewis, Joshua R, Lill, Christina, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Livshits, Gregory, Ljunggren, Östen, Loos, Ruth J F, Lorentzon, Mattias, Luan, Jian'an, Luben, Robert N, Malkin, Ida, McGuigan, Fiona E, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Michaëlsson, Karl, Mitchell, Braxton D, Morris, Andrew P, Mosekilde, Leif, Nethander, Maria, Newman, Anne B, O'Connell, Jeffery R, Oostra, Ben A, Orwoll, Eric S, Palotie, Aarno, Peacock, Munro, Perola, Markus, Peters, Annette, Prince, Richard L, Psaty, Bruce M, Räikkönen, Katri, Ralston, Stuart H, Ripatti, Samuli, Rivadeneira, Fernando, Robbins, John A, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Satterfield, Suzanne, Schipf, Sabine, Shin, Chan Soo, Smith, Albert V, Smith, Shad B, Soranzo, Nicole, Spector, Timothy D, Stančáková, Alena, Stefansson, Kari, Steinhagen-Thiessen, Elisabeth, Stolk, Lisette, Streeten, Elizabeth A, Styrkarsdottir, Unnur, Swart, Karin M A, Thompson, Patricia, Thomson, Cynthia A, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tikkanen, Emmi, Tranah, Gregory J, Uitterlinden, André G, van Duijn, Cornelia M, van Schoor, Natasja M, Vandenput, Liesbeth, Vollenweider, Peter, Völzke, Henry, Wactawski-Wende, Jean, Walker, Mark, J Wareham, Nicholas, Waterworth, Dawn, Weedon, Michael N, Wichmann, H-Erich, Widen, Elisabeth, Williams, Frances M K, Wilson, James F, Wright, Nicole C, Yerges-Armstrong, Laura M, Yu, Lei, Zhang, Weihua, Zhao, Jing Hua, Zhou, Yanhua, Nielson, Carrie M, Harris, Tamara B, Demissie, Serkalem, Kiel, Douglas P, and Ohlsson, Claes

Published
2019
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7. Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Prescribing Trends of Medicinal Products Containing Valproate: An Interrupted Time Series Study

Author

Abtahi, Shahab, Pajouheshnia, Romin, Durán, Carlos E, Riera-Arnau, Judit, Gamba, Magdalena, Alsina, Ema, Hoxhaj, Vjola, Andersen, Morten, Bartolini, Claudia, Kristiansen, Sarah Brøgger, Brown, Jeremy, Hallgreen, Christine Erikstrup, Garcia-Poza, Patricia, Gardarsdottir, Helga, Gini, Rosa, Girardi, Anna, Holthuis, Emily, Huerta, Consuelo, Ibánez, Luisa, Limoncella, Giorgio, Martín-Pérez, Mar, Paoletti, Olga, Roberto, Giuseppe, Souverein, Patrick, Swart, Karin M A, Wing, Kevin, Sturkenboom, Miriam, Klungel, Olaf, Abtahi, Shahab, Pajouheshnia, Romin, Durán, Carlos E, Riera-Arnau, Judit, Gamba, Magdalena, Alsina, Ema, Hoxhaj, Vjola, Andersen, Morten, Bartolini, Claudia, Kristiansen, Sarah Brøgger, Brown, Jeremy, Hallgreen, Christine Erikstrup, Garcia-Poza, Patricia, Gardarsdottir, Helga, Gini, Rosa, Girardi, Anna, Holthuis, Emily, Huerta, Consuelo, Ibánez, Luisa, Limoncella, Giorgio, Martín-Pérez, Mar, Paoletti, Olga, Roberto, Giuseppe, Souverein, Patrick, Swart, Karin M A, Wing, Kevin, Sturkenboom, Miriam, and Klungel, Olaf

Abstract

Introduction: Due to established teratogenicity of valproates, the EU risk minimisation measures (RMMs) with a pregnancy prevention programme (PPP) for valproate were updated in March 2018. Objectives: To investigate the effectiveness of the 2018 EU RMMs on valproate utilisation in five European countries/regions. Methods: A multi-database, times series study of females of childbearing potential (12–55 years) was conducted using electronic medical records from five countries/regions (01.01.2010–31.12.2020): Denmark, Tuscany (Italy), Spain, the Netherlands, and the UK. Clinical and demographic information from each database was transformed to the ConcePTION Common Data Model, quality checks were conducted and a distributed analysis was performed using common scripts. Incident and prevalent use of valproate, proportion of discontinuers and switchers to alternative medicine, frequency of contraception coverage during valproate use, and occurrence of pregnancies during valproate exposure were estimated per month. Interrupted time series analyses were conducted to estimate the level or trend change in the outcome measures. Results: We included 69,533 valproate users from 9,699,371 females of childbearing potential from the five participating centres. A significant decline in prevalent use of valproates was observed in Tuscany, Italy (mean difference post-intervention −7.7%), Spain (−11.3%), and UK (−5.9%) and a non-significant decline in the Netherlands (−3.3%), but no decline in incident use after the 2018 RMMs compared to the period before. The monthly proportion of compliant valproate prescriptions/dispensings with a contraceptive coverage was low (<25%), with an increase after the 2018 RMMs only in the Netherlands (mean difference post-intervention 12%). There was no significant increase in switching rates from valproates to alternative medicine after the 2018 intervention in any of the countries/regions. We observed a substantial number of concurrent pregnanci

Published
2023

8. Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Prescribing Trends of Medicinal Products Containing Valproate: An Interrupted Time Series Study

Author

Pharmacoepidemiology and Clinical Pharmacology, Afd Pharmacoepi & Clinical Pharmacology, PECP - Centre for Pharmacoepidemiology, Abtahi, Shahab, Pajouheshnia, Romin, Durán, Carlos E, Riera-Arnau, Judit, Gamba, Magdalena, Alsina, Ema, Hoxhaj, Vjola, Andersen, Morten, Bartolini, Claudia, Kristiansen, Sarah Brøgger, Brown, Jeremy, Hallgreen, Christine Erikstrup, Garcia-Poza, Patricia, Gardarsdottir, Helga, Gini, Rosa, Girardi, Anna, Holthuis, Emily, Huerta, Consuelo, Ibánez, Luisa, Limoncella, Giorgio, Martín-Pérez, Mar, Paoletti, Olga, Roberto, Giuseppe, Souverein, Patrick, Swart, Karin M A, Wing, Kevin, Sturkenboom, Miriam, Klungel, Olaf, Pharmacoepidemiology and Clinical Pharmacology, Afd Pharmacoepi & Clinical Pharmacology, PECP - Centre for Pharmacoepidemiology, Abtahi, Shahab, Pajouheshnia, Romin, Durán, Carlos E, Riera-Arnau, Judit, Gamba, Magdalena, Alsina, Ema, Hoxhaj, Vjola, Andersen, Morten, Bartolini, Claudia, Kristiansen, Sarah Brøgger, Brown, Jeremy, Hallgreen, Christine Erikstrup, Garcia-Poza, Patricia, Gardarsdottir, Helga, Gini, Rosa, Girardi, Anna, Holthuis, Emily, Huerta, Consuelo, Ibánez, Luisa, Limoncella, Giorgio, Martín-Pérez, Mar, Paoletti, Olga, Roberto, Giuseppe, Souverein, Patrick, Swart, Karin M A, Wing, Kevin, Sturkenboom, Miriam, and Klungel, Olaf

Published
2023

9. Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Prescribing Trends of Medicinal Products Containing Valproate: An Interrupted Time Series Study

Author

RWE/Causal inference, Epi Infectieziekten Team 2, Apotheek O&O&O, Child Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Data Science & Biostatistiek, Abtahi, Shahab, Pajouheshnia, Romin, Durán, Carlos E, Riera-Arnau, Judit, Gamba, Magdalena, Alsina, Ema, Hoxhaj, Vjola, Andersen, Morten, Bartolini, Claudia, Kristiansen, Sarah Brøgger, Brown, Jeremy, Hallgreen, Christine Erikstrup, Garcia-Poza, Patricia, Gardarsdottir, Helga, Gini, Rosa, Girardi, Anna, Holthuis, Emily, Huerta, Consuelo, Ibánez, Luisa, Limoncella, Giorgio, Martín-Pérez, Mar, Paoletti, Olga, Roberto, Giuseppe, Souverein, Patrick, Swart, Karin M A, Wing, Kevin, Sturkenboom, Miriam, Klungel, Olaf, RWE/Causal inference, Epi Infectieziekten Team 2, Apotheek O&O&O, Child Health, Infection & Immunity, Regenerative Medicine and Stem Cells, Data Science & Biostatistiek, Abtahi, Shahab, Pajouheshnia, Romin, Durán, Carlos E, Riera-Arnau, Judit, Gamba, Magdalena, Alsina, Ema, Hoxhaj, Vjola, Andersen, Morten, Bartolini, Claudia, Kristiansen, Sarah Brøgger, Brown, Jeremy, Hallgreen, Christine Erikstrup, Garcia-Poza, Patricia, Gardarsdottir, Helga, Gini, Rosa, Girardi, Anna, Holthuis, Emily, Huerta, Consuelo, Ibánez, Luisa, Limoncella, Giorgio, Martín-Pérez, Mar, Paoletti, Olga, Roberto, Giuseppe, Souverein, Patrick, Swart, Karin M A, Wing, Kevin, Sturkenboom, Miriam, and Klungel, Olaf

Published
2023

10. Vitamin D deficiency in Europe: pandemic?

Author

Cashman, Kevin D, Dowling, Kirsten G, Škrabáková, Zuzana, Gonzalez-Gross, Marcela, Valtueña, Jara, De Henauw, Stefaan, Moreno, Luis, Damsgaard, Camilla T, Michaelsen, Kim F, Mølgaard, Christian, Jorde, Rolf, Grimnes, Guri, Moschonis, George, Mavrogianni, Christina, Manios, Yannis, Thamm, Michael, Mensink, Gert BM, Rabenberg, Martina, Busch, Markus A, Cox, Lorna, Meadows, Sarah, Goldberg, Gail, Prentice, Ann, Dekker, Jacqueline M, Nijpels, Giel, Pilz, Stefan, Swart, Karin M, van Schoor, Natasja M, Lips, Paul, Eiriksdottir, Gudny, Gudnason, Vilmundur, Cotch, Mary Frances, Koskinen, Seppo, Lamberg-Allardt, Christel, Durazo-Arvizu, Ramon A, Sempos, Christopher T, and Kiely, Mairead

Published
2016
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11. Impact of 2018 EU Risk Minimisation Measures and Revised Pregnancy Prevention Programme on Utilisation and Prescribing Trends of Medicinal Products Containing Valproate:An Interrupted Time Series Study

Author

Abtahi, Shahab, Pajouheshnia, Romin, Durán, Carlos E, Riera-Arnau, Judit, Gamba, Magdalena, Alsina, Ema, Hoxhaj, Vjola, Andersen, Morten, Bartolini, Claudia, Kristiansen, Sarah Brøgger, Brown, Jeremy, Hallgreen, Christine Erikstrup, Garcia-Poza, Patricia, Gardarsdottir, Helga, Gini, Rosa, Girardi, Anna, Holthuis, Emily, Huerta, Consuelo, Ibánez, Luisa, Limoncella, Giorgio, Martín-Pérez, Mar, Paoletti, Olga, Roberto, Giuseppe, Souverein, Patrick, Swart, Karin M A, Wing, Kevin, Sturkenboom, Miriam, Klungel, Olaf, Pharmacoepidemiology and Clinical Pharmacology, and Afd Pharmacoepi & Clinical Pharmacology

Subjects
Italy/epidemiology, Valproic Acid/adverse effects, Pharmacology, Contraception, Pregnancy, Humans, Female, Interrupted Time Series Analysis, Pharmacology (medical), Toxicology, Europe/epidemiology
Abstract

Introduction: Due to established teratogenicity of valproates, the EU risk minimisation measures (RMMs) with a pregnancy prevention programme (PPP) for valproate were updated in March 2018. Objectives: To investigate the effectiveness of the 2018 EU RMMs on valproate utilisation in five European countries/regions. Methods: A multi-database, times series study of females of childbearing potential (12–55 years) was conducted using electronic medical records from five countries/regions (01.01.2010–31.12.2020): Denmark, Tuscany (Italy), Spain, the Netherlands, and the UK. Clinical and demographic information from each database was transformed to the ConcePTION Common Data Model, quality checks were conducted and a distributed analysis was performed using common scripts. Incident and prevalent use of valproate, proportion of discontinuers and switchers to alternative medicine, frequency of contraception coverage during valproate use, and occurrence of pregnancies during valproate exposure were estimated per month. Interrupted time series analyses were conducted to estimate the level or trend change in the outcome measures. Results: We included 69,533 valproate users from 9,699,371 females of childbearing potential from the five participating centres. A significant decline in prevalent use of valproates was observed in Tuscany, Italy (mean difference post-intervention −7.7%), Spain (−11.3%), and UK (−5.9%) and a non-significant decline in the Netherlands (−3.3%), but no decline in incident use after the 2018 RMMs compared to the period before. The monthly proportion of compliant valproate prescriptions/dispensings with a contraceptive coverage was low (

Published
2023
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13. Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries

Author

Bots, Sophie H., primary, Riera-Arnau, Judit, additional, Belitser, Svetlana V., additional, Messina, Davide, additional, Aragón, Maria, additional, Alsina, Ema, additional, Douglas, Ian J., additional, Durán, Carlos E., additional, García-Poza, Patricia, additional, Gini, Rosa, additional, Herings, Ron M. C., additional, Huerta, Consuelo, additional, Sisay, Malede Mequanent, additional, Martín-Pérez, Mar, additional, Martin, Ivonne, additional, Overbeek, Jetty A., additional, Paoletti, Olga, additional, Pallejà-Millán, Meritxell, additional, Schultze, Anna, additional, Souverein, Patrick, additional, Swart, Karin M. A., additional, Villalobos, Felipe, additional, Klungel, Olaf H., additional, and Sturkenboom, Miriam C. J. M., additional

Published
2022
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15. Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries

Author

Bots, Sophie H, Riera-Arnau, Judit, Belitser, Svetlana V, Messina, Davide, Aragón, Maria, Alsina, Ema, Douglas, Ian J, Durán, Carlos E, García-Poza, Patricia, Gini, Rosa, Herings, Ron M C, Huerta, Consuelo, Sisay, Malede Mequanent, Martín-Pérez, Mar, Martin, Ivonne, Overbeek, Jetty A, Paoletti, Olga, Pallejà-Millán, Meritxell, Schultze, Anna, Souverein, Patrick, Swart, Karin M A, Villalobos, Felipe, Klungel, Olaf H, Sturkenboom, Miriam C J M, Bots, Sophie H, Riera-Arnau, Judit, Belitser, Svetlana V, Messina, Davide, Aragón, Maria, Alsina, Ema, Douglas, Ian J, Durán, Carlos E, García-Poza, Patricia, Gini, Rosa, Herings, Ron M C, Huerta, Consuelo, Sisay, Malede Mequanent, Martín-Pérez, Mar, Martin, Ivonne, Overbeek, Jetty A, Paoletti, Olga, Pallejà-Millán, Meritxell, Schultze, Anna, Souverein, Patrick, Swart, Karin M A, Villalobos, Felipe, Klungel, Olaf H, and Sturkenboom, Miriam C J M

Abstract

Background: Estimates of the association between COVID-19 vaccines and myo-/pericarditis risk vary widely across studies due to scarcity of events, especially in age- and sex-stratified analyses. Methods: Population-based cohort study with nested self-controlled risk interval (SCRI) using healthcare data from five European databases. Individuals were followed from 01/01/2020 until end of data availability (31/12/2021 latest). Outcome was first myo-/pericarditis diagnosis. Exposures were first and second dose of Pfizer, AstraZeneca, Moderna, and Janssen COVID-19 vaccines. Baseline incidence rates (IRs), and vaccine- and dose-specific IRs and rate differences were calculated from the cohort The SCRI calculated calendar time-adjusted IR ratios (IRR), using a 60-day pre-vaccination control period and dose-specific 28-day risk windows. IRRs were pooled using random effects meta-analysis. Findings: Over 35 million individuals (49·2% women, median age 39-49 years) were included, of which 57·4% received at least one COVID-19 vaccine dose. Baseline incidence of myocarditis was low. Myocarditis IRRs were elevated after vaccination in those aged < 30 years, after both Pfizer vaccine doses (IRR = 3·3, 95%CI 1·2-9.4; 7·8, 95%CI 2·6-23·5, respectively) and Moderna vaccine dose 2 (IRR = 6·1, 95%CI 1·1-33·5). An effect of AstraZeneca vaccine dose 2 could not be excluded (IRR = 2·42, 95%CI 0·96-6·07). Pericarditis was not associated with vaccination. Interpretation: mRNA-based COVID-19 vaccines and potentially AstraZeneca are associated with increased myocarditis risk in younger individuals, although absolute incidence remains low. More data on children (≤ 11 years) are needed.

Published
2022

16. Myocarditis and pericarditis associated with SARS-CoV-2 vaccines: A population-based descriptive cohort and a nested self-controlled risk interval study using electronic health care data from four European countries

Author

Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Bots, Sophie H, Riera-Arnau, Judit, Belitser, Svetlana V, Messina, Davide, Aragón, Maria, Alsina, Ema, Douglas, Ian J, Durán, Carlos E, García-Poza, Patricia, Gini, Rosa, Herings, Ron M C, Huerta, Consuelo, Sisay, Malede Mequanent, Martín-Pérez, Mar, Martin, Ivonne, Overbeek, Jetty A, Paoletti, Olga, Pallejà-Millán, Meritxell, Schultze, Anna, Souverein, Patrick, Swart, Karin M A, Villalobos, Felipe, Klungel, Olaf H, Sturkenboom, Miriam C J M, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, Bots, Sophie H, Riera-Arnau, Judit, Belitser, Svetlana V, Messina, Davide, Aragón, Maria, Alsina, Ema, Douglas, Ian J, Durán, Carlos E, García-Poza, Patricia, Gini, Rosa, Herings, Ron M C, Huerta, Consuelo, Sisay, Malede Mequanent, Martín-Pérez, Mar, Martin, Ivonne, Overbeek, Jetty A, Paoletti, Olga, Pallejà-Millán, Meritxell, Schultze, Anna, Souverein, Patrick, Swart, Karin M A, Villalobos, Felipe, Klungel, Olaf H, and Sturkenboom, Miriam C J M

Published
2022

18. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Author

Zillikens, M. Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M., Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L., Kutalik, Zoltán, Luan, Jian’an, Malkin, Ida, Ried, Janina S., Smith, Albert V., Thorleifsson, Gudmar, Vandenput, Liesbeth, Hua Zhao, Jing, Zhang, Weihua, Aghdassi, Ali, Åkesson, Kristina, Amin, Najaf, Baier, Leslie J., Barroso, Inês, Bennett, David A., Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B., Buchman, Aron S., Byberg, Liisa, Campbell, Harry, Campos Obanda, Natalia, Cauley, Jane A., Cawthon, Peggy M., Cederberg, Henna, Chen, Zhao, Cho, Nam H., Jin Choi, Hyung, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R., De Jager, Philip L., Demuth, Ilja, Dhonukshe-Rutten, Rosalie A. M., Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W., Erdos, Mike, Eriksson, Johan G., Eriksson, Joel, Estrada, Karol, Evans, Daniel S., Feitosa, Mary F., Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L., Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L., Hayward, Caroline, Hofman, Albert, Hoffman, Eric P., Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J., Hubbard, Alan, Huffman, Kim M., Husted, Lise B., Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M., Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O., Klopp, Norman, Kloth, Jacqueline S. L., Koistinen, Heikki A., Kraus, William E., Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L., Launer, Lenore J., Lee, Jong-Young, Lerch, Markus M., Lewis, Joshua R., Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Liu, Tian, Liu, Youfang, Ljunggren, Östen, Lorentzon, Mattias, Luben, Robert N., Maixner, William, McGuigan, Fiona E., Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Melov, Simon, Michaëlsson, Karl, Mitchell, Braxton D., Morris, Andrew P., Mosekilde, Leif, Newman, Anne, Nielson, Carrie M., O’Connell, Jeffrey R., Oostra, Ben A., Orwoll, Eric S., Palotie, Aarno, Parker, Stephen C. J., Peacock, Munro, Perola, Markus, Peters, Annette, Polasek, Ozren, Prince, Richard L., Räikkönen, Katri, Ralston, Stuart H., Ripatti, Samuli, Robbins, John A., Rotter, Jerome I., Rudan, Igor, Salomaa, Veikko, Satterfield, Suzanne, Schadt, Eric E., Schipf, Sabine, Scott, Laura, Sehmi, Joban, Shen, Jian, Soo Shin, Chan, Sigurdsson, Gunnar, Smith, Shad, Soranzo, Nicole, Stančáková, Alena, Steinhagen-Thiessen, Elisabeth, Streeten, Elizabeth A., Styrkarsdottir, Unnur, Swart, Karin M. A., Tan, Sian-Tsung, Tarnopolsky, Mark A., Thompson, Patricia, Thomson, Cynthia A., Thorsteinsdottir, Unnur, Tikkanen, Emmi, Tranah, Gregory J., Tuomilehto, Jaakko, van Schoor, Natasja M., Verma, Arjun, Vollenweider, Peter, Völzke, Henry, Wactawski-Wende, Jean, Walker, Mark, Weedon, Michael N., Welch, Ryan, Wichmann, H.-Erich, Widen, Elisabeth, Williams, Frances M. K., Wilson, James F., Wright, Nicole C., Xie, Weijia, Yu, Lei, Zhou, Yanhua, Chambers, John C., Döring, Angela, van Duijn, Cornelia M., Econs, Michael J., Gudnason, Vilmundur, Kooner, Jaspal S., Psaty, Bruce M., Spector, Timothy D., Stefansson, Kari, Rivadeneira, Fernando, Uitterlinden, André G., Wareham, Nicholas J., Ossowski, Vicky, Waterworth, Dawn, Loos, Ruth J. F., Karasik, David, Harris, Tamara B., Ohlsson, Claes, and Kiel, Douglas P.

Published
2017
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19. Effectiveness of COVID-19 Vaccines in Adults with Diabetes Mellitus: A Systematic Review.

Author

van den Berg, Jesse M., Remmelzwaal, Sharon, Blom, Marieke T., van Hoek, Beryl A. C. E., Swart, Karin M. A., Overbeek, Jetty A., Burchell, George L., Herings, Ron M. C., and Elders, Petra J. M.

Subjects
VACCINE effectiveness, COVID-19 vaccines, DIABETES, BREAKTHROUGH infections, COVID-19
Abstract

Persons with diabetes mellitus may have an increased risk of severe illness or death from COVID-19 compared to persons without diabetes. Prior studies indicate that immune response and thus vaccine effectiveness might be lower in persons with diabetes. We aimed to systematically review the effectiveness of COVID-19 vaccines in adults with diabetes. Pubmed, Embase, Web of Science and Cochrane Library were searched for studies that evaluated the effectiveness of COVID-19 vaccines in adults with diabetes, published before 4 March 2022. Risk of bias in the included studies was evaluated using the ROBINS-I tool. At least two reviewers conducted the study selection, data extraction, and risk of bias assessment independently. After screening of 2196 studies, a total of 17 articles were included. Six different COVID-19 vaccines (Ad5-nCoV-S, AZD1222, BNT162b2, CoronaVac, JNJ-78436735, and mRNA-1273) were included in the synthesis. Vaccine effectiveness was reported for SARS-CoV-2 infection, symptomatic COVID-19, hospitalization, and death, and ranged from 24 to 96% in persons with diabetes, and from 33 to 97% in total study populations; effectiveness was generally lower for persons with diabetes. Odds ratios for breakthrough infection or severe COVID-19 ranged from 1.03 to 2.41 in vaccinated persons with diabetes compared to persons without diabetes. Even though the included studies were very heterogeneous, results from the synthesis indicate that effectiveness of COVID-19 vaccines might be lower in persons with diabetes. More research is needed on the comparison of vaccine effectiveness between persons with and without diabetes, and the effectiveness of repeat COVID-19 vaccinations. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Development and validation of an algorithm to estimate the risk of severe complications of COVID-19: a retrospective cohort study in primary care in the Netherlands

Author

Herings, Ron M C, primary, Swart, Karin M A, additional, van der Zeijst, Bernard A M, additional, van der Heijden, Amber A, additional, van der Velden, Koos, additional, Hiddink, Eric G, additional, Heymans, Martijn W, additional, Herings, Reinier A R, additional, van Hout, Hein P J, additional, Beulens, Joline W J, additional, Nijpels, Giel, additional, and Elders, Petra J M, additional

Published
2021
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21. Non-linear associations between serum 25-OH vitamin D and indices of arterial stiffness and arteriosclerosis in an older population

Author

van Dijk, Suzanne C., Sohl, Evelien, Oudshoorn, Christian, Enneman, Anke W., Ham, Annelies C., Swart, Karin M. A., van Wijngaarden, Janneke P., Brouwer-Brolsma, Elske M., van der Zwaluw, Nikita L., Uitterlinden, Andre G., de Groot, Lisette C. P. G. M., Dhonukshe-Rutten, Rosalie A. M., Lips, Paul, van Schoor, Natasja M., Blom, Henk J., Geleijnse, Johanna M., Feskens, Edith J., Smulders, Yvo M., Zillikens, M. Carola, de Jongh, Renate T., van den Meiracker, Anton H., Mattace Raso, Francesco U. S., and van der Velde, Nathalie

Published
2015
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22. Predicting hospital admissions from individual patient data (IPD): an applied example to explore key elements driving external validity

Author

Meid, Andreas Daniel, primary, Gonzalez-Gonzalez, Ana Isabel, additional, Dinh, Truc Sophia, additional, Blom, Jeanet, additional, van den Akker, Marjan, additional, Elders, Petra, additional, Thiem, Ulrich, additional, Küllenberg de Gaudry, Daniela, additional, Swart, Karin M A, additional, Rudolf, Henrik, additional, Bosch-Lenders, Donna, additional, Trampisch, Hans J, additional, Meerpohl, Joerg J, additional, Gerlach, Ferdinand M, additional, Flaig, Benno, additional, Kom, Ghainsom, additional, Snell, Kym I E, additional, Perera, Rafael, additional, Haefeli, Walter Emil, additional, Glasziou, Paul, additional, and Muth, Christiane, additional

Published
2021
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23. Predicting hospital admissions from individual patient data (IPD): an applied example to explore key elements driving external validity

Author

Meid, Andreas, González-González, Ana I., Dinh, Truc Sophia, Blom, Jeanette Wilhelmina, Akker, Marjan van den, Elders, Petra, Thiem, Ulrich, Küllenberg de Gaudry, Daniela, Swart, Karin M. A., Rudolf, Henrik, Bosch-Lenders, Donna, Trampisch, Hans Joachim, Meerpohl, Jörg J., Gerlach, Ferdinand M., Flaig, Benno, Kom, Ghainsom D., Snell, Kym I. E., Perera, Rafael, Haefeli, Walter E., Glasziou, Paul, Muth, Christiane, Meid, Andreas, González-González, Ana I., Dinh, Truc Sophia, Blom, Jeanette Wilhelmina, Akker, Marjan van den, Elders, Petra, Thiem, Ulrich, Küllenberg de Gaudry, Daniela, Swart, Karin M. A., Rudolf, Henrik, Bosch-Lenders, Donna, Trampisch, Hans Joachim, Meerpohl, Jörg J., Gerlach, Ferdinand M., Flaig, Benno, Kom, Ghainsom D., Snell, Kym I. E., Perera, Rafael, Haefeli, Walter E., Glasziou, Paul, and Muth, Christiane

Abstract

Objective To explore factors that potentially impact external validation performance while developing and validating a prognostic model for hospital admissions (HAs) in complex older general practice patients. Study design and setting Using individual participant data from four cluster-randomised trials conducted in the Netherlands and Germany, we used logistic regression to develop a prognostic model to predict all-cause HAs within a 6-month follow-up period. A stratified intercept was used to account for heterogeneity in baseline risk between the studies. The model was validated both internally and by using internal-external cross-validation (IECV). Results Prior HAs, physical components of the health-related quality of life comorbidity index, and medication-related variables were used in the final model. While achieving moderate discriminatory performance, internal bootstrap validation revealed a pronounced risk of overfitting. The results of the IECV, in which calibration was highly variable even after accounting for between-study heterogeneity, agreed with this finding. Heterogeneity was equally reflected in differing baseline risk, predictor effects and absolute risk predictions. Conclusions Predictor effect heterogeneity and differing baseline risk can explain the limited external performance of HA prediction models. With such drivers known, model adjustments in external validation settings (eg, intercept recalibration, complete updating) can be applied more purposefully. Trial registration number PROSPERO id: CRD42018088129.

Published
2021

24. Discovery of predictors of sudden cardiac arrest in diabetes: rationale and outline of the RESCUED (REcognition of Sudden Cardiac arrest vUlnErability in Diabetes) project

Author

van Dongen, Laura H, primary, Harms, Peter P, additional, Hoogendoorn, Mark, additional, Zimmerman, Dominic S, additional, Lodder, Elisabeth M, additional, 't Hart, Leen M, additional, Herings, Ron, additional, van Weert, Henk C P M, additional, Nijpels, Giel, additional, Swart, Karin M A, additional, van der Heijden, Amber A, additional, Blom, Marieke T, additional, Elders, Petra J, additional, and Tan, Hanno L, additional

Published
2021
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25. 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. 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., Mller-Nurasyid, Martina, 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. 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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26. Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts

Author

Aspelund, Thor, primary, Grübler, Martin R., additional, Smith, Albert V., additional, Gudmundsson, Elias F., additional, Keppel, Martin, additional, Cotch, Mary Frances, additional, Harris, Tamara B., additional, Jorde, Rolf, additional, Grimnes, Guri, additional, Joakimsen, Ragnar, additional, Schirmer, Henrik, additional, Wilsgaard, Tom, additional, Mathiesen, Ellisiv B., additional, Njølstad, Inger, additional, Løchen, Maja-Lisa, additional, März, Winfried, additional, Kleber, Marcus E., additional, Tomaschitz, Andreas, additional, Grove-Laugesen, Diana, additional, Rejnmark, Lars, additional, Swart, Karin M. A., additional, Brouwer, Ingeborg A., additional, Lips, Paul, additional, Van Schoor, Natasja M., additional, Sempos, Christopher T., additional, Durazo-Arvizu, Ramón A., additional, Škrabáková, Zuzana, additional, Dowling, Kirsten G., additional, Cashman, Kevin D., additional, Kiely, Mairead, additional, Pilz, Stefan, additional, Gudnason, Vilmundur, additional, and Eiriksdottir, Gudny, additional

Published
2019
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27. Beta-blocker use and fall risk in older individuals:Original results from two studies with meta-analysis

Author

Ham, Annelies C., van Dijk, Suzanne C., Swart, Karin M. A., Enneman, Anke W., van der Zwaluw, Nikita L., Brouwer-Brolsma, Elske M., van Schoor, Natasja M., Carola Zillikens, M., Lips, Paul, de Groot, Lisette C. P. G. M., Hofman, Albert, Witkamp, Renger F., Uitterlinden, André G., Stricker, Bruno H., van der Velde, Nathalie, Epidemiology, Internal Medicine, Surgery, General practice, APH - Aging & Later Life, Epidemiology and Data Science, Internal medicine, Geriatrics, and AMS - Amsterdam Movement Sciences

Subjects
Global Nutrition, Wereldvoeding, Meta-analysis, CYP2D6, β-blockers, Falls, Nutritional Biology, VLAG
Abstract

Aims: To investigate the association between use of β-blockers and β-blocker characteristics – selectivity, lipid solubility, intrinsic sympathetic activity (ISA) and CYP2D6 enzyme metabolism – and fall risk. Methods: Data from two prospective studies were used, including community-dwelling individuals, n = 7662 (the Rotterdam Study) and 2407 (B-PROOF), all aged ≥55 years. Fall incidents were recorded prospectively. Time-varying β-blocker use was determined using pharmacy dispensing records. Cox proportional hazard models adjusted for age and sex were applied to determine the association between β-blocker use, their characteristics – selectivity, lipid solubility, ISA and CYP2D6 enzyme metabolism – and fall risk. The results of the studies were combined using meta-analyses. Results: In total 2917 participants encountered a fall during a total follow-up time of 89 529 years. Meta-analysis indicated no association between use of any β-blocker, compared to nonuse, and fall risk, hazard ratio (HR) = 0.97 [95% confidence interval (CI) 0.88–1.06]. Use of a selective β-blocker was also not associated with fall risk, HR = 0.92 (95%CI 0.83–1.01). Use of a nonselective β-blocker was associated with an increased fall risk, HR = 1.22 (95%CI 1.01–1.48). Other β-blocker characteristics including lipid solubility and CYP2D6 enzyme metabolism were not associated with fall risk. Conclusion: Our study suggests that use of a nonselective β-blocker, contrary to selective β-blockers, is associated with an increased fall risk in an older population. In clinical practice, β-blockers have been shown effective for a variety of cardiovascular indications. However, fall risk should be considered when prescribing a β-blocker in this age group, and the pros and cons for β-blocker classes should be taken into consideration.

Published
2017
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28. Erratum : Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Author

Zillikens, M Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M, Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L, Kutalik, Zoltán, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Hua Zhao, Jing, Zhang, Weihua, Aghdassi, Ali, Åkesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Inês, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos Obanda, Natalia, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Jin Choi, Hyung, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie A M, Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W, Erdos, Mike, Eriksson, Johan G, Eriksson, Joel, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L, Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L, Hayward, Caroline, Hofman, Albert, Hoffman, Eric P, Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J, Hubbard, Alan, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline S L, Koistinen, Heikki A, Kraus, William E, Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Launer, Lenore J, Lee, Jong-Young, Lerch, Markus M, Lewis, Joshua R, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Liu, Tian, Liu, Youfang, Ljunggren, Östen, Lorentzon, Mattias, Luben, Robert N, Maixner, William, McGuigan, Fiona E, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Melov, Simon, Michaëlsson, Karl, Mitchell, Braxton D, Morris, Andrew P, Mosekilde, Leif, Newman, Anne, Nielson, Carrie M, O'Connell, Jeffrey R, Oostra, Ben A, Orwoll, Eric S, Palotie, Aarno, Parker, Stephen C J, Peacock, Munro, Perola, Markus, Peters, Annette, Polasek, Ozren, Prince, Richard L, Räikkönen, Katri, Ralston, Stuart H, Ripatti, Samuli, Robbins, John A, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Satterfield, Suzanne, Schadt, Eric E, Schipf, Sabine, Scott, Laura, Sehmi, Joban, Shen, Jian, Soo Shin, Chan, Sigurdsson, Gunnar, Smith, Shad, Soranzo, Nicole, Stančáková, Alena, Steinhagen-Thiessen, Elisabeth, Streeten, Elizabeth A, Styrkarsdottir, Unnur, Swart, Karin M A, Tan, Sian-Tsung, Tarnopolsky, Mark A, Thompson, Patricia, Thomson, Cynthia A, Thorsteinsdottir, Unnur, Tikkanen, Emmi, Tranah, Gregory J, Tuomilehto, Jaakko, van Schoor, Natasja M, Verma, Arjun, Vollenweider, Peter, Völzke, Henry, Wactawski-Wende, Jean, Walker, Mark, Weedon, Michael N, Welch, Ryan, Wichmann, H-Erich, Widen, Elisabeth, Williams, Frances M K, Wilson, James F, Wright, Nicole C, Xie, Weijia, Yu, Lei, Zhou, Yanhua, Chambers, John C, Döring, Angela, van Duijn, Cornelia M, Econs, Michael J, Gudnason, Vilmundur, Kooner, Jaspal S, Psaty, Bruce M, Spector, Timothy D, Stefansson, Kari, Rivadeneira, Fernando, Uitterlinden, André G, Wareham, Nicholas J, Ossowski, Vicky, Waterworth, Dawn, Loos, Ruth J F, Karasik, David, Harris, Tamara B, Ohlsson, Claes, Kiel, Douglas P, Zillikens, M Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M, Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L, Kutalik, Zoltán, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Hua Zhao, Jing, Zhang, Weihua, Aghdassi, Ali, Åkesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Inês, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos Obanda, Natalia, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Jin Choi, Hyung, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie A M, Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W, Erdos, Mike, Eriksson, Johan G, Eriksson, Joel, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L, Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L, Hayward, Caroline, Hofman, Albert, Hoffman, Eric P, Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J, Hubbard, Alan, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline S L, Koistinen, Heikki A, Kraus, William E, Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Launer, Lenore J, Lee, Jong-Young, Lerch, Markus M, Lewis, Joshua R, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Liu, Tian, Liu, Youfang, Ljunggren, Östen, Lorentzon, Mattias, Luben, Robert N, Maixner, William, McGuigan, Fiona E, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Melov, Simon, Michaëlsson, Karl, Mitchell, Braxton D, Morris, Andrew P, Mosekilde, Leif, Newman, Anne, Nielson, Carrie M, O'Connell, Jeffrey R, Oostra, Ben A, Orwoll, Eric S, Palotie, Aarno, Parker, Stephen C J, Peacock, Munro, Perola, Markus, Peters, Annette, Polasek, Ozren, Prince, Richard L, Räikkönen, Katri, Ralston, Stuart H, Ripatti, Samuli, Robbins, John A, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Satterfield, Suzanne, Schadt, Eric E, Schipf, Sabine, Scott, Laura, Sehmi, Joban, Shen, Jian, Soo Shin, Chan, Sigurdsson, Gunnar, Smith, Shad, Soranzo, Nicole, Stančáková, Alena, Steinhagen-Thiessen, Elisabeth, Streeten, Elizabeth A, Styrkarsdottir, Unnur, Swart, Karin M A, Tan, Sian-Tsung, Tarnopolsky, Mark A, Thompson, Patricia, Thomson, Cynthia A, Thorsteinsdottir, Unnur, Tikkanen, Emmi, Tranah, Gregory J, Tuomilehto, Jaakko, van Schoor, Natasja M, Verma, Arjun, Vollenweider, Peter, Völzke, Henry, Wactawski-Wende, Jean, Walker, Mark, Weedon, Michael N, Welch, Ryan, Wichmann, H-Erich, Widen, Elisabeth, Williams, Frances M K, Wilson, James F, Wright, Nicole C, Xie, Weijia, Yu, Lei, Zhou, Yanhua, Chambers, John C, Döring, Angela, van Duijn, Cornelia M, Econs, Michael J, Gudnason, Vilmundur, Kooner, Jaspal S, Psaty, Bruce M, Spector, Timothy D, Stefansson, Kari, Rivadeneira, Fernando, Uitterlinden, André G, Wareham, Nicholas J, Ossowski, Vicky, Waterworth, Dawn, Loos, Ruth J F, Karasik, David, Harris, Tamara B, Ohlsson, Claes, and Kiel, Douglas P

Abstract

A correction to this article has been published and is linked from the publisher´s HTML version of the article.

Published
2017
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29. Folate and vitamin B12-related biomarkers in relation to brain volumes

Author

van der Zwaluw, Nikita L., Brouwer-Brolsma, Elske M., van de Rest, Ondine, van Wijngaarden, Janneke P., In ’t Veld, Paulette H., Kourie, Daniella I., Swart, Karin M A, Enneman, Anke W., van Dijk, Suzanne C., van der Velde, Nathalie, Kessels, Roy P C, Smeets, Paul A M, Kok, Frans J., Dhonukshe-Rutten, Rosalie A M, de Groot, Lisette C P G M, van der Zwaluw, Nikita L., Brouwer-Brolsma, Elske M., van de Rest, Ondine, van Wijngaarden, Janneke P., In ’t Veld, Paulette H., Kourie, Daniella I., Swart, Karin M A, Enneman, Anke W., van Dijk, Suzanne C., van der Velde, Nathalie, Kessels, Roy P C, Smeets, Paul A M, Kok, Frans J., Dhonukshe-Rutten, Rosalie A M, and de Groot, Lisette C P G M

Published
2017

30. Folate and vitamin B12-related biomarkers in relation to brain volumes

Author

Brain, Beeldverwerking ISI, van der Zwaluw, Nikita L., Brouwer-Brolsma, Elske M., van de Rest, Ondine, van Wijngaarden, Janneke P., In ’t Veld, Paulette H., Kourie, Daniella I., Swart, Karin M A, Enneman, Anke W., van Dijk, Suzanne C., van der Velde, Nathalie, Kessels, Roy P C, Smeets, Paul A M, Kok, Frans J., Dhonukshe-Rutten, Rosalie A M, de Groot, Lisette C P G M, Brain, Beeldverwerking ISI, van der Zwaluw, Nikita L., Brouwer-Brolsma, Elske M., van de Rest, Ondine, van Wijngaarden, Janneke P., In ’t Veld, Paulette H., Kourie, Daniella I., Swart, Karin M A, Enneman, Anke W., van Dijk, Suzanne C., van der Velde, Nathalie, Kessels, Roy P C, Smeets, Paul A M, Kok, Frans J., Dhonukshe-Rutten, Rosalie A M, and de Groot, Lisette C P G M

Published
2017

31. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Author

Zillikens, M Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M, Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L, Kutalik, Zoltán, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Hua Zhao, Jing, Zhang, Weihua, Aghdassi, Ali, Åkesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Inês, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos Obanda, Natalia, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Jin Choi, Hyung, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie A M, Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W, Erdos, Mike, Eriksson, Johan G, Eriksson, Joel, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L, Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L, Hayward, Caroline, Hofman, Albert, Hoffman, Eric P, Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J, Hubbard, Alan, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline S L, Koistinen, Heikki A, Kraus, William E, Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Launer, Lenore J, Lee, Jong-Young, Lerch, Markus M, Lewis, Joshua R, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Liu, Tian, Liu, Youfang, Ljunggren, Östen, Lorentzon, Mattias, Luben, Robert N, Maixner, William, McGuigan, Fiona E, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Melov, Simon, Michaëlsson, Karl, Mitchell, Braxton D, Morris, Andrew P, Mosekilde, Leif, Newman, Anne, Nielson, Carrie M, O'Connell, Jeffrey R, Oostra, Ben A, Orwoll, Eric S, Palotie, Aarno, Parker, Stephan, Peacock, Munro, Perola, Markus, Peters, Annette, Polasek, Ozren, Prince, Richard L, Räikkönen, Katri, Ralston, Stuart H, Ripatti, Samuli, Robbins, John A, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Satterfield, Suzanne, Schadt, Eric E, Schipf, Sabine, Scott, Laura, Sehmi, Joban, Shen, Jian, Soo Shin, Chan, Sigurdsson, Gunnar, Smith, Shad, Soranzo, Nicole, Stančáková, Alena, Steinhagen-Thiessen, Elisabeth, Streeten, Elizabeth A, Styrkarsdottir, Unnur, Swart, Karin M A, Tan, Sian-Tsung, Tarnopolsky, Mark A, Thompson, Patricia, Thomson, Cynthia A, Thorsteinsdottir, Unnur, Tikkanen, Emmi, Tranah, Gregory J, Tuomilehto, Jaakko, van Schoor, Natasja M, Verma, Arjun, Vollenweider, Peter, Völzke, Henry, Wactawski-Wende, Jean, Walker, Mark, Weedon, Michael N, Welch, Ryan, Wichmann, H-Erich, Widen, Elisabeth, Williams, Frances M K, Wilson, James F, Wright, Nicole C, Xie, Weijia, Yu, Lei, Zhou, Yanhua, Chambers, John C, Döring, Angela, van Duijn, Cornelia M, Econs, Michael J, Gudnason, Vilmundur, Kooner, Jaspal S, Psaty, Bruce M, Spector, Timothy D, Stefansson, Kari, Rivadeneira, Fernando, Uitterlinden, André G, Wareham, Nicholas J, Ossowski, Vicky, Waterworth, Dawn, Loos, Ruth J F, Karasik, David, Harris, Tamara B, Ohlsson, Claes, Kiel, Douglas P, Zillikens, M Carola, Demissie, Serkalem, Hsu, Yi-Hsiang, Yerges-Armstrong, Laura M, Chou, Wen-Chi, Stolk, Lisette, Livshits, Gregory, Broer, Linda, Johnson, Toby, Koller, Daniel L, Kutalik, Zoltán, Luan, Jian'an, Malkin, Ida, Ried, Janina S, Smith, Albert V, Thorleifsson, Gudmar, Vandenput, Liesbeth, Hua Zhao, Jing, Zhang, Weihua, Aghdassi, Ali, Åkesson, Kristina, Amin, Najaf, Baier, Leslie J, Barroso, Inês, Bennett, David A, Bertram, Lars, Biffar, Rainer, Bochud, Murielle, Boehnke, Michael, Borecki, Ingrid B, Buchman, Aron S, Byberg, Liisa, Campbell, Harry, Campos Obanda, Natalia, Cauley, Jane A, Cawthon, Peggy M, Cederberg, Henna, Chen, Zhao, Cho, Nam H, Jin Choi, Hyung, Claussnitzer, Melina, Collins, Francis, Cummings, Steven R, De Jager, Philip L, Demuth, Ilja, Dhonukshe-Rutten, Rosalie A M, Diatchenko, Luda, Eiriksdottir, Gudny, Enneman, Anke W, Erdos, Mike, Eriksson, Johan G, Eriksson, Joel, Estrada, Karol, Evans, Daniel S, Feitosa, Mary F, Fu, Mao, Garcia, Melissa, Gieger, Christian, Girke, Thomas, Glazer, Nicole L, Grallert, Harald, Grewal, Jagvir, Han, Bok-Ghee, Hanson, Robert L, Hayward, Caroline, Hofman, Albert, Hoffman, Eric P, Homuth, Georg, Hsueh, Wen-Chi, Hubal, Monica J, Hubbard, Alan, Huffman, Kim M, Husted, Lise B, Illig, Thomas, Ingelsson, Erik, Ittermann, Till, Jansson, John-Olov, Jordan, Joanne M, Jula, Antti, Karlsson, Magnus, Khaw, Kay-Tee, Kilpeläinen, Tuomas O, Klopp, Norman, Kloth, Jacqueline S L, Koistinen, Heikki A, Kraus, William E, Kritchevsky, Stephen, Kuulasmaa, Teemu, Kuusisto, Johanna, Laakso, Markku, Lahti, Jari, Lang, Thomas, Langdahl, Bente L, Launer, Lenore J, Lee, Jong-Young, Lerch, Markus M, Lewis, Joshua R, Lind, Lars, Lindgren, Cecilia, Liu, Yongmei, Liu, Tian, Liu, Youfang, Ljunggren, Östen, Lorentzon, Mattias, Luben, Robert N, Maixner, William, McGuigan, Fiona E, Medina-Gomez, Carolina, Meitinger, Thomas, Melhus, Håkan, Mellström, Dan, Melov, Simon, Michaëlsson, Karl, Mitchell, Braxton D, Morris, Andrew P, Mosekilde, Leif, Newman, Anne, Nielson, Carrie M, O'Connell, Jeffrey R, Oostra, Ben A, Orwoll, Eric S, Palotie, Aarno, Parker, Stephan, Peacock, Munro, Perola, Markus, Peters, Annette, Polasek, Ozren, Prince, Richard L, Räikkönen, Katri, Ralston, Stuart H, Ripatti, Samuli, Robbins, John A, Rotter, Jerome I, Rudan, Igor, Salomaa, Veikko, Satterfield, Suzanne, Schadt, Eric E, Schipf, Sabine, Scott, Laura, Sehmi, Joban, Shen, Jian, Soo Shin, Chan, Sigurdsson, Gunnar, Smith, Shad, Soranzo, Nicole, Stančáková, Alena, Steinhagen-Thiessen, Elisabeth, Streeten, Elizabeth A, Styrkarsdottir, Unnur, Swart, Karin M A, Tan, Sian-Tsung, Tarnopolsky, Mark A, Thompson, Patricia, Thomson, Cynthia A, Thorsteinsdottir, Unnur, Tikkanen, Emmi, Tranah, Gregory J, Tuomilehto, Jaakko, van Schoor, Natasja M, Verma, Arjun, Vollenweider, Peter, Völzke, Henry, Wactawski-Wende, Jean, Walker, Mark, Weedon, Michael N, Welch, Ryan, Wichmann, H-Erich, Widen, Elisabeth, Williams, Frances M K, Wilson, James F, Wright, Nicole C, Xie, Weijia, Yu, Lei, Zhou, Yanhua, Chambers, John C, Döring, Angela, van Duijn, Cornelia M, Econs, Michael J, Gudnason, Vilmundur, Kooner, Jaspal S, Psaty, Bruce M, Spector, Timothy D, Stefansson, Kari, Rivadeneira, Fernando, Uitterlinden, André G, Wareham, Nicholas J, Ossowski, Vicky, Waterworth, Dawn, Loos, Ruth J F, Karasik, David, Harris, Tamara B, Ohlsson, Claes, and Kiel, Douglas P

Abstract

Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10(-8)) or suggestively genome wide (p < 2.3 × 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

Published
2017

32. Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass

Author

Zillikens, M. Carola, primary, Demissie, Serkalem, additional, Hsu, Yi-Hsiang, additional, Yerges-Armstrong, Laura M., additional, Chou, Wen-Chi, additional, Stolk, Lisette, additional, Livshits, Gregory, additional, Broer, Linda, additional, Johnson, Toby, additional, Koller, Daniel L., additional, Kutalik, Zoltán, additional, Luan, Jian’an, additional, Malkin, Ida, additional, Ried, Janina S., additional, Smith, Albert V., additional, Thorleifsson, Gudmar, additional, Vandenput, Liesbeth, additional, Hua Zhao, Jing, additional, Zhang, Weihua, additional, Aghdassi, Ali, additional, Åkesson, Kristina, additional, Amin, Najaf, additional, Baier, Leslie J., additional, Barroso, Inês, additional, Bennett, David A., additional, Bertram, Lars, additional, Biffar, Rainer, additional, Bochud, Murielle, additional, Boehnke, Michael, additional, Borecki, Ingrid B., additional, Buchman, Aron S., additional, Byberg, Liisa, additional, Campbell, Harry, additional, Campos Obanda, Natalia, additional, Cauley, Jane A., additional, Cawthon, Peggy M., additional, Cederberg, Henna, additional, Chen, Zhao, additional, Cho, Nam H., additional, Jin Choi, Hyung, additional, Claussnitzer, Melina, additional, Collins, Francis, additional, Cummings, Steven R., additional, De Jager, Philip L., additional, Demuth, Ilja, additional, Dhonukshe-Rutten, Rosalie A. M., additional, Diatchenko, Luda, additional, Eiriksdottir, Gudny, additional, Enneman, Anke W., additional, Erdos, Mike, additional, Eriksson, Johan G., additional, Eriksson, Joel, additional, Estrada, Karol, additional, Evans, Daniel S., additional, Feitosa, Mary F., additional, Fu, Mao, additional, Garcia, Melissa, additional, Gieger, Christian, additional, Girke, Thomas, additional, Glazer, Nicole L., additional, Grallert, Harald, additional, Grewal, Jagvir, additional, Han, Bok-Ghee, additional, Hanson, Robert L., additional, Hayward, Caroline, additional, Hofman, Albert, additional, Hoffman, Eric P., additional, Homuth, Georg, additional, Hsueh, Wen-Chi, additional, Hubal, Monica J., additional, Hubbard, Alan, additional, Huffman, Kim M., additional, Husted, Lise B., additional, Illig, Thomas, additional, Ingelsson, Erik, additional, Ittermann, Till, additional, Jansson, John-Olov, additional, Jordan, Joanne M., additional, Jula, Antti, additional, Karlsson, Magnus, additional, Khaw, Kay-Tee, additional, Kilpeläinen, Tuomas O., additional, Klopp, Norman, additional, Kloth, Jacqueline S. L., additional, Koistinen, Heikki A., additional, Kraus, William E., additional, Kritchevsky, Stephen, additional, Kuulasmaa, Teemu, additional, Kuusisto, Johanna, additional, Laakso, Markku, additional, Lahti, Jari, additional, Lang, Thomas, additional, Langdahl, Bente L., additional, Launer, Lenore J., additional, Lee, Jong-Young, additional, Lerch, Markus M., additional, Lewis, Joshua R., additional, Lind, Lars, additional, Lindgren, Cecilia, additional, Liu, Yongmei, additional, Liu, Tian, additional, Liu, Youfang, additional, Ljunggren, Östen, additional, Lorentzon, Mattias, additional, Luben, Robert N., additional, Maixner, William, additional, McGuigan, Fiona E., additional, Medina-Gomez, Carolina, additional, Meitinger, Thomas, additional, Melhus, Håkan, additional, Mellström, Dan, additional, Melov, Simon, additional, Michaëlsson, Karl, additional, Mitchell, Braxton D., additional, Morris, Andrew P., additional, Mosekilde, Leif, additional, Newman, Anne, additional, Nielson, Carrie M., additional, O’Connell, Jeffrey R., additional, Oostra, Ben A., additional, Orwoll, Eric S., additional, Palotie, Aarno, additional, Parker, Stephen C. J., additional, Peacock, Munro, additional, Perola, Markus, additional, Peters, Annette, additional, Polasek, Ozren, additional, Prince, Richard L., additional, Räikkönen, Katri, additional, Ralston, Stuart H., additional, Ripatti, Samuli, additional, Robbins, John A., additional, Rotter, Jerome I., additional, Rudan, Igor, additional, Salomaa, Veikko, additional, Satterfield, Suzanne, additional, Schadt, Eric E., additional, Schipf, Sabine, additional, Scott, Laura, additional, Sehmi, Joban, additional, Shen, Jian, additional, Soo Shin, Chan, additional, Sigurdsson, Gunnar, additional, Smith, Shad, additional, Soranzo, Nicole, additional, Stančáková, Alena, additional, Steinhagen-Thiessen, Elisabeth, additional, Streeten, Elizabeth A., additional, Styrkarsdottir, Unnur, additional, Swart, Karin M. A., additional, Tan, Sian-Tsung, additional, Tarnopolsky, Mark A., additional, Thompson, Patricia, additional, Thomson, Cynthia A., additional, Thorsteinsdottir, Unnur, additional, Tikkanen, Emmi, additional, Tranah, Gregory J., additional, Tuomilehto, Jaakko, additional, van Schoor, Natasja M., additional, Verma, Arjun, additional, Vollenweider, Peter, additional, Völzke, Henry, additional, Wactawski-Wende, Jean, additional, Walker, Mark, additional, Weedon, Michael N., additional, Welch, Ryan, additional, Wichmann, H.-Erich, additional, Widen, Elisabeth, additional, Williams, Frances M. K., additional, Wilson, James F., additional, Wright, Nicole C., additional, Xie, Weijia, additional, Yu, Lei, additional, Zhou, Yanhua, additional, Chambers, John C., additional, Döring, Angela, additional, van Duijn, Cornelia M., additional, Econs, Michael J., additional, Gudnason, Vilmundur, additional, Kooner, Jaspal S., additional, Psaty, Bruce M., additional, Spector, Timothy D., additional, Stefansson, Kari, additional, Rivadeneira, Fernando, additional, Uitterlinden, André G., additional, Wareham, Nicholas J., additional, Ossowski, Vicky, additional, Waterworth, Dawn, additional, Loos, Ruth J. F., additional, Karasik, David, additional, Harris, Tamara B., additional, Ohlsson, Claes, additional, and Kiel, Douglas P., additional

Published
2017
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33. Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium

Author

Gaksch, Martin, primary, Jorde, Rolf, additional, Grimnes, Guri, additional, Joakimsen, Ragnar, additional, Schirmer, Henrik, additional, Wilsgaard, Tom, additional, Mathiesen, Ellisiv B., additional, Njølstad, Inger, additional, Løchen, Maja-Lisa, additional, März, Winfried, additional, Kleber, Marcus E., additional, Tomaschitz, Andreas, additional, Grübler, Martin, additional, Eiriksdottir, Gudny, additional, Gudmundsson, Elias F., additional, Harris, Tamara B., additional, Cotch, Mary F., additional, Aspelund, Thor, additional, Gudnason, Vilmundur, additional, Rutters, Femke, additional, Beulens, Joline W. J., additional, van ‘t Riet, Esther, additional, Nijpels, Giel, additional, Dekker, Jacqueline M., additional, Grove-Laugesen, Diana, additional, Rejnmark, Lars, additional, Busch, Markus A., additional, Mensink, Gert B. M., additional, Scheidt-Nave, Christa, additional, Thamm, Michael, additional, Swart, Karin M. A., additional, Brouwer, Ingeborg A., additional, Lips, Paul, additional, van Schoor, Natasja M., additional, Sempos, Christopher T., additional, Durazo-Arvizu, Ramón A., additional, Škrabáková, Zuzana, additional, Dowling, Kirsten G., additional, Cashman, Kevin D., additional, Kiely, Mairead, additional, and Pilz, Stefan, additional

Published
2017
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34. Folic Acid and Vitamin B12 Supplementation and the Risk of Cancer: Long-term Follow-up of the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) Trial.

Author

Araghi, Sadaf Oliai, Kiefte-de Jong, Jessica C., van Dijk, Suzanne C., Swart, Karin M. A., van Laarhoven, Hanneke W., van Schoor, Natasja M., de Groot, Lisette C. P. G. M., Lemmens, Valery, Stricker, Bruno H., Uitterlinden, André G., and van der Velde, Nathalie

Abstract

Background: Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial. Methods: Long-term follow-up of B-PROOF trial participants (N = 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 µg) and vitamin B12 (500 µg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00-C97 for all cancers (except C44 for skin cancer), and C18-C20 for colorectal cancer. Results: Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00-1.53, P = 0.05]. B vitamins were significantly associated with a higher risk of colorectal cancer [43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08-2.90, P = 0.02]. Conclusions: Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer. Impact: Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency. [ABSTRACT FROM AUTHOR]

Published
2019
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35. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author

Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, Loos, Ruth J F, Lu, Yingchang, Day, Felix R, Gustafsson, Stefan, Buchkovich, Martin L, Na, Jianbo, Bataille, Veronique, Cousminer, Diana L, Dastani, Zari, Drong, Alexander W, Esko, Tõnu, Evans, David M, Falchi, Mario, Feitosa, Mary F, Ferreira, Teresa, Hedman, Åsa K, Haring, Robin, Hysi, Pirro G, Iles, Mark M, Justice, Anne E, Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Mägi, Reedik, Perry, John R B, Pers, Tune H, Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M, Scott, William R, Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A E, Walker, Ryan W, Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J L, Bellis, Claire, Bonnefond, Amélie, Borodulin, Katja, Buchman, Aron S, Cederholm, Tommy, Choh, Audrey C, Choi, Hyung Jin, Curran, Joanne E, de Groot, Lisette C P G M, De Jager, Philip L, Dhonukshe-Rutten, Rosalie A M, Enneman, Anke W, Eury, Elodie, Evans, Daniel S, Forsen, Tom, Friedrich, Nele, Fumeron, Frédéric, Garcia, Melissa E, Gärtner, Simone, Han, Bok-Ghee, Havulinna, Aki S, Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W, Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Mateo Leach, Irene, Lee, Christine G, Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stéphane, Loh, Marie, Lyytikäinen, Leo-Pekka, Medina-Gomez, Carolina, Michaëlsson, Karl, Nalls, Mike A, Nielson, Carrie M, Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polašek, Ozren, Ripatti, Samuli, Sarzynski, Mark A, Shin, Chan Soo, Narančić, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M A, Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M, Verweij, Niek, Wright, Alan F, Yu, Lei, Zmuda, Joseph M, Eklund, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U, Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Männistö, Satu, Palmer, Cameron D, Ried, Janina S, Scott, Robert A, Stancáková, Alena, Wagner, Peter J, Demirkan, Ayse, Döring, Angela, Gudnason, Vilmundur, Kiel, Douglas P, Kühnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R, Oostra, Ben A, Shuldiner, Alan R, Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M, Vollenweider, Peter, White, Charles C, Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S, Forouhi, Nita G, Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jørgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A, Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O, Wareham, Nicholas J, Bennett, David A, Bertram, Lars, Blangero, John, Blüher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H, Cummings, Steven R, Czerwinski, Stefan A, Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G, Ferrucci, Luigi, Franco, Oscar H, Froguel, Philippe, Gansevoort, Ron T, Hansen, Torben, Harris, Tamara B, Hastie, Nicholas, Heliövaara, Markku, Hofman, Albert, Jordan, Joanne M, Jula, Antti, Kähönen, Mika, Kajantie, Eero, Knekt, Paul B, Koskinen, Seppo, Kovacs, Peter, Lehtimäki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S, Osmond, Clive, Perola, Markus, Pérusse, Louis, Raitakari, Olli T, Rankinen, Tuomo, Rao, D C, Rice, Treva K, Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sørensen, Thorkild I A, Stumvoll, Michael, Tönjes, Anke, Towne, Bradford, Tranah, Gregory J, Tremblay, Angelo, Uitterlinden, André G, van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S, Vitart, Veronique, Vohl, Marie-Claude, Völzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F, Yengo, Loïc, Bishop, D Timothy, Borecki, Ingrid B, Chambers, John C, Cupples, L Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S, Franke, Lude, Han, Jiali, Hunter, David J, Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C, Kooner, Jaspal S, McCarthy, Mark I, Murabito, Joanne M, Morris, Andrew P, Bishop, Julia A N, North, Kari E, Ohlsson, Claes, Ong, Ken K, Prokopenko, Inga, Richards, J Brent, Schadt, Eric E, Spector, Tim D, Widén, Elisabeth, Willer, Cristen J, Yang, Jian, Ingelsson, Erik, Mohlke, Karen L, Hirschhorn, Joel N, Pospisilik, John Andrew, Zillikens, M Carola, Lindgren, Cecilia, Kilpeläinen, Tuomas Oskari, and Loos, Ruth J F

Abstract

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

Published
2016
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37. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author

University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Clinicum, University of Helsinki, Institute of Behavioural Sciences, University of Helsinki, Hospital for Children and Adolescents, Lu, Yingchang, Day, Felix R., Gustafsson, Stefan, Buchkovich, Martin L., Na, Jianbo, Bataille, Veronique, Cousminer, Diana L., Dastani, Zari, Drong, Alexander W., Esko, Tonu, Evans, David M., Falchi, Mario, Feitosa, Mary F., Ferreira, Teresa, Hedman, Asa K., Haring, Robin, Hysi, Pirro G., Iles, Mark M., Justice, Anne E., Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Magi, Reedik, Perry, John R. B., Pers, Tune H., Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M., Scott, William R., Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A. E., Walker, Ryan W., Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J. L., Bellis, Claire, Bonnefond, Amelie, Borodulin, Katja, Buchman, Aron S., Cederholm, Tommy, Choh, Audrey C., Choi, Hyung Jin, Curran, Joanne E., de Groot, Lisette C. P. G. M., De Jager, Philip L., Dhonukshe-Rutten, Rosalie A. M., Enneman, Anke W., Eury, Elodie, Evans, Daniel S., Forsen, Tom, Friedrich, Nele, Fumeron, Frederic, Garcia, Melissa E., Gartner, Simone, Han, Bok-Ghee, Havulinna, Aki S., Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W., Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Leach, Irene Mateo, Lee, Christine G., Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stephane, Loh, Marie, Lyytikainen, Leo-Pekka, Medina-Gomez, Carolina, Michaelsson, Karl, Nalls, Mike A., Nielson, Carrie M., Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polasek, Ozren, Ripatti, Samuli, Sarzynski, Mark A., Shin, Chan Soo, Narancic, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M. A., Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M., Verweij, Niek, Wright, Alan F., Yu, Lei, Zmuda, Joseph M., Pellikka, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U., Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Mannisto, Satu, Palmer, Cameron D., Ried, Janina S., Scott, Robert A., Stancakova, Alena, Wagner, Peter J., Demirkan, Ayse, Doring, Angela, Gudnason, Vilmundur, Kiel, Douglas P., Kuhnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R., Oostra, Ben A., Shuldiner, Alan R., Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M., Vollenweider, Peter, White, Charles C., Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S., Forouhi, Nita G., Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jorgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A., Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O., Wareham, Nicholas J., Bennett, David A., Bertram, Lars, Blangero, John, Bluher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H., Cummings, Steven R., Czerwinski, Stefan A., Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G., Ferrucci, Luigi, Franco, Oscar H., Froguel, Philippe, Gansevoort, Ron T., Hansen, Torben, Harris, Tamara B., Hastie, Nicholas, Heliovaara, Markku, Hofman, Albert, Jordan, Joanne M., Jula, Antti, Kahonen, Mika, Kajantie, Eero, Knekt, Paul B., Koskinen, Seppo, Kovacs, Peter, Lehtimaki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S., Osmond, Clive, Perola, Markus, Perusse, Louis, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sorensen, Thorkild I. A., Stumvoll, Michael, Tonjes, Anke, Towne, Bradford, Tranah, Gregory J., Tremblay, Angelo, Uitterlinden, Andre G., van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S., Vitart, Veronique, Vohl, Marie-Claude, Volzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F., Yengo, Loic, Bishop, D. Timothy, Borecki, Ingrid B., Chambers, John C., Cupples, L. Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S., Franke, Lude, Han, Jiali, Hunter, David J., Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C., Kooner, Jaspal S., McCarthy, Mark I., Murabito, Joanne M., Morris, Andrew P., Bishop, Julia A. N., North, Kari E., Ohlsson, Claes, Ong, Ken K., Prokopenko, Inga, Richards, J. Brent, Schadt, Eric E., Spector, Tim D., Widen, Elisabeth, Willer, Cristen J., Yang, Jian, Ingelsson, Erik, Mohlke, Karen L., Hirschhorn, Joel N., Pospisilik, John Andrew, Zillikens, M. Carola, Lindgren, Cecilia, Kilpelainen, Tuomas Oskari, Loos, Ruth J. F., University of Helsinki, Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Clinicum, University of Helsinki, Institute of Behavioural Sciences, University of Helsinki, Hospital for Children and Adolescents, Lu, Yingchang, Day, Felix R., Gustafsson, Stefan, Buchkovich, Martin L., Na, Jianbo, Bataille, Veronique, Cousminer, Diana L., Dastani, Zari, Drong, Alexander W., Esko, Tonu, Evans, David M., Falchi, Mario, Feitosa, Mary F., Ferreira, Teresa, Hedman, Asa K., Haring, Robin, Hysi, Pirro G., Iles, Mark M., Justice, Anne E., Kanoni, Stavroula, Lagou, Vasiliki, Li, Rui, Li, Xin, Locke, Adam, Lu, Chen, Magi, Reedik, Perry, John R. B., Pers, Tune H., Qi, Qibin, Sanna, Marianna, Schmidt, Ellen M., Scott, William R., Shungin, Dmitry, Teumer, Alexander, Vinkhuyzen, Anna A. E., Walker, Ryan W., Westra, Harm-Jan, Zhang, Mingfeng, Zhang, Weihua, Zhao, Jing Hua, Zhu, Zhihong, Afzal, Uzma, Ahluwalia, Tarunveer Singh, Bakker, Stephan J. L., Bellis, Claire, Bonnefond, Amelie, Borodulin, Katja, Buchman, Aron S., Cederholm, Tommy, Choh, Audrey C., Choi, Hyung Jin, Curran, Joanne E., de Groot, Lisette C. P. G. M., De Jager, Philip L., Dhonukshe-Rutten, Rosalie A. M., Enneman, Anke W., Eury, Elodie, Evans, Daniel S., Forsen, Tom, Friedrich, Nele, Fumeron, Frederic, Garcia, Melissa E., Gartner, Simone, Han, Bok-Ghee, Havulinna, Aki S., Hayward, Caroline, Hernandez, Dena, Hillege, Hans, Ittermann, Till, Kent, Jack W., Kolcic, Ivana, Laatikainen, Tiina, Lahti, Jari, Leach, Irene Mateo, Lee, Christine G., Lee, Jong-Young, Liu, Tian, Liu, Youfang, Lobbens, Stephane, Loh, Marie, Lyytikainen, Leo-Pekka, Medina-Gomez, Carolina, Michaelsson, Karl, Nalls, Mike A., Nielson, Carrie M., Oozageer, Laticia, Pascoe, Laura, Paternoster, Lavinia, Polasek, Ozren, Ripatti, Samuli, Sarzynski, Mark A., Shin, Chan Soo, Narancic, Nina Smolej, Spira, Dominik, Srikanth, Priya, Steinhagen-Thiessen, Elisabeth, Sung, Yun Ju, Swart, Karin M. A., Taittonen, Leena, Tanaka, Toshiko, Tikkanen, Emmi, van der Velde, Nathalie, van Schoor, Natasja M., Verweij, Niek, Wright, Alan F., Yu, Lei, Zmuda, Joseph M., Pellikka, Niina, Forrester, Terrence, Grarup, Niels, Jackson, Anne U., Kristiansson, Kati, Kuulasmaa, Teemu, Kuusisto, Johanna, Lichtner, Peter, Luan, Jian'an, Mahajan, Anubha, Mannisto, Satu, Palmer, Cameron D., Ried, Janina S., Scott, Robert A., Stancakova, Alena, Wagner, Peter J., Demirkan, Ayse, Doring, Angela, Gudnason, Vilmundur, Kiel, Douglas P., Kuhnel, Brigitte, Mangino, Massimo, Mcknight, Barbara, Menni, Cristina, O'Connell, Jeffrey R., Oostra, Ben A., Shuldiner, Alan R., Song, Kijoung, Vandenput, Liesbeth, van Duijn, Cornelia M., Vollenweider, Peter, White, Charles C., Boehnke, Michael, Boettcher, Yvonne, Cooper, Richard S., Forouhi, Nita G., Gieger, Christian, Grallert, Harald, Hingorani, Aroon, Jorgensen, Torben, Jousilahti, Pekka, Kivimaki, Mika, Kumari, Meena, Laakso, Markku, Langenberg, Claudia, Linneberg, Allan, Luke, Amy, Mckenzie, Colin A., Palotie, Aarno, Pedersen, Oluf, Peters, Annette, Strauch, Konstantin, Tayo, Bamidele O., Wareham, Nicholas J., Bennett, David A., Bertram, Lars, Blangero, John, Bluher, Matthias, Bouchard, Claude, Campbell, Harry, Cho, Nam H., Cummings, Steven R., Czerwinski, Stefan A., Demuth, Ilja, Eckardt, Rahel, Eriksson, Johan G., Ferrucci, Luigi, Franco, Oscar H., Froguel, Philippe, Gansevoort, Ron T., Hansen, Torben, Harris, Tamara B., Hastie, Nicholas, Heliovaara, Markku, Hofman, Albert, Jordan, Joanne M., Jula, Antti, Kahonen, Mika, Kajantie, Eero, Knekt, Paul B., Koskinen, Seppo, Kovacs, Peter, Lehtimaki, Terho, Lind, Lars, Liu, Yongmei, Orwoll, Eric S., Osmond, Clive, Perola, Markus, Perusse, Louis, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Rivadeneira, Fernando, Rudan, Igor, Salomaa, Veikko, Sorensen, Thorkild I. A., Stumvoll, Michael, Tonjes, Anke, Towne, Bradford, Tranah, Gregory J., Tremblay, Angelo, Uitterlinden, Andre G., van der Harst, Pim, Vartiainen, Erkki, Viikari, Jorma S., Vitart, Veronique, Vohl, Marie-Claude, Volzke, Henry, Walker, Mark, Wallaschofski, Henri, Wild, Sarah, Wilson, James F., Yengo, Loic, Bishop, D. Timothy, Borecki, Ingrid B., Chambers, John C., Cupples, L. Adrienne, Dehghan, Abbas, Deloukas, Panos, Fatemifar, Ghazaleh, Fox, Caroline, Furey, Terrence S., Franke, Lude, Han, Jiali, Hunter, David J., Karjalainen, Juha, Karpe, Fredrik, Kaplan, Robert C., Kooner, Jaspal S., McCarthy, Mark I., Murabito, Joanne M., Morris, Andrew P., Bishop, Julia A. N., North, Kari E., Ohlsson, Claes, Ong, Ken K., Prokopenko, Inga, Richards, J. Brent, Schadt, Eric E., Spector, Tim D., Widen, Elisabeth, Willer, Cristen J., Yang, Jian, Ingelsson, Erik, Mohlke, Karen L., Hirschhorn, Joel N., Pospisilik, John Andrew, Zillikens, M. Carola, Lindgren, Cecilia, Kilpelainen, Tuomas Oskari, and Loos, Ruth J. F.

Abstract

To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P <5 x 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

Published
2016

38. Feasibility of using head and neck CT imaging to assess skeletal muscle mass in head and neck cancer patients

Author

Verpleegafdeling Mondz/Kaakchir. D5 Oost, Brain, MS Hoofd-Hals Chirurgische Oncologie, MS Radiotherapie, Zorgeenheid KNO Medisch, Cancer, Zorgeenheid Traumatologie, Infection & Immunity, Swartz, Justin E., Pothen, Ajit J., Wegner, Inge, Smid, Ernst J., Swart, Karin M A, de Bree, Remco, Leenen, Loek P H, Grolman, Wilko, Verpleegafdeling Mondz/Kaakchir. D5 Oost, Brain, MS Hoofd-Hals Chirurgische Oncologie, MS Radiotherapie, Zorgeenheid KNO Medisch, Cancer, Zorgeenheid Traumatologie, Infection & Immunity, Swartz, Justin E., Pothen, Ajit J., Wegner, Inge, Smid, Ernst J., Swart, Karin M A, de Bree, Remco, Leenen, Loek P H, and Grolman, Wilko

Published
2016

39. Vitamin D deficiency in Europe:pandemic?

Author

Cashman, Kevin D., Dowling, Kirsten G, Škrabáková, Zuzana, Gonzalez-Gross, Marcela, Valtueña, Jara, De Henauw, Stefaan, Moreno, Luis A., Damsgaard, Camilla Trab, Michaelsen, Kim F., Mølgaard, Christian, Jorde, Rolf, Grimnes, Guri, Moschonis, George, Mavrogianni, Christina, Manios, Yannis, Thamm, Michael, Mensink, Gert BM, Rabenberg, Martina, Busch, Markus A, Cox, Lorna, Meadows, Sarah, Goldberg, Gail, Prentice, Ann, Dekker, Jacqueline M, Nijpels, Giel, Pilz, Stefan, Swart, Karin M A, van Schoor, Natasja M, Lips, Paul, Eiriksdottir, Gudny, Gudnason, Vilmundur, Cotch, Mary Frances, Koskinen, Seppo, Lamberg-Allardt, Christel, Durazo-Arvizu, Ramon A, Sempos, Christopher T, Kiely, Mairead, Cashman, Kevin D., Dowling, Kirsten G, Škrabáková, Zuzana, Gonzalez-Gross, Marcela, Valtueña, Jara, De Henauw, Stefaan, Moreno, Luis A., Damsgaard, Camilla Trab, Michaelsen, Kim F., Mølgaard, Christian, Jorde, Rolf, Grimnes, Guri, Moschonis, George, Mavrogianni, Christina, Manios, Yannis, Thamm, Michael, Mensink, Gert BM, Rabenberg, Martina, Busch, Markus A, Cox, Lorna, Meadows, Sarah, Goldberg, Gail, Prentice, Ann, Dekker, Jacqueline M, Nijpels, Giel, Pilz, Stefan, Swart, Karin M A, van Schoor, Natasja M, Lips, Paul, Eiriksdottir, Gudny, Gudnason, Vilmundur, Cotch, Mary Frances, Koskinen, Seppo, Lamberg-Allardt, Christel, Durazo-Arvizu, Ramon A, Sempos, Christopher T, and Kiely, Mairead

Abstract

BACKGROUND: Vitamin D deficiency has been described as being pandemic, but serum 25-hydroxyvitamin D [25(OH)D] distribution data for the European Union are of very variable quality. The NIH-led international Vitamin D Standardization Program (VDSP) has developed protocols for standardizing existing 25(OH)D values from national health/nutrition surveys.OBJECTIVE: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D deficiency in Europe.DESIGN: The VDSP protocols were applied in 14 population studies [reanalysis of subsets of serum 25(OH)D in 11 studies and complete analysis of all samples from 3 studies that had not previously measured it] by using certified liquid chromatography-tandem mass spectrometry on biobanked sera. These data were combined with standardized serum 25(OH)D data from 4 previously standardized studies (for a total n = 55,844). Prevalence estimates of vitamin D deficiency [using various serum 25(OH)D thresholds] were generated on the basis of standardized 25(OH)D data.RESULTS: An overall pooled estimate, irrespective of age group, ethnic mix, and latitude of study populations, showed that 13.0% of the 55,844 European individuals had serum 25(OH)D concentrations <30 nmol/L on average in the year, with 17.7% and 8.3% in those sampled during the extended winter (October-March) and summer (April-November) periods, respectively. According to an alternate suggested definition of vitamin D deficiency (<50 nmol/L), the prevalence was 40.4%. Dark-skinned ethnic subgroups had much higher (3- to 71-fold) prevalence of serum 25(OH)D <30 nmol/L than did white populations.CONCLUSIONS: Vitamin D deficiency is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective.

Published
2016

40. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

Author

Lu, Yingchang, primary, Day, Felix R., additional, Gustafsson, Stefan, additional, Buchkovich, Martin L., additional, Na, Jianbo, additional, Bataille, Veronique, additional, Cousminer, Diana L., additional, Dastani, Zari, additional, Drong, Alexander W., additional, Esko, Tõnu, additional, Evans, David M., additional, Falchi, Mario, additional, Feitosa, Mary F., additional, Ferreira, Teresa, additional, Hedman, Åsa K., additional, Haring, Robin, additional, Hysi, Pirro G., additional, Iles, Mark M., additional, Justice, Anne E., additional, Kanoni, Stavroula, additional, Lagou, Vasiliki, additional, Li, Rui, additional, Li, Xin, additional, Locke, Adam, additional, Lu, Chen, additional, Mägi, Reedik, additional, Perry, John R. B., additional, Pers, Tune H., additional, Qi, Qibin, additional, Sanna, Marianna, additional, Schmidt, Ellen M., additional, Scott, William R., additional, Shungin, Dmitry, additional, Teumer, Alexander, additional, Vinkhuyzen, Anna A. E., additional, Walker, Ryan W., additional, Westra, Harm-Jan, additional, Zhang, Mingfeng, additional, Zhang, Weihua, additional, Zhao, Jing Hua, additional, Zhu, Zhihong, additional, Afzal, Uzma, additional, Ahluwalia, Tarunveer Singh, additional, Bakker, Stephan J. L., additional, Bellis, Claire, additional, Bonnefond, Amélie, additional, Borodulin, Katja, additional, Buchman, Aron S., additional, Cederholm, Tommy, additional, Choh, Audrey C., additional, Choi, Hyung Jin, additional, Curran, Joanne E., additional, de Groot, Lisette C. P. G. M., additional, De Jager, Philip L., additional, Dhonukshe-Rutten, Rosalie A. M., additional, Enneman, Anke W., additional, Eury, Elodie, additional, Evans, Daniel S., additional, Forsen, Tom, additional, Friedrich, Nele, additional, Fumeron, Frédéric, additional, Garcia, Melissa E., additional, Gärtner, Simone, additional, Han, Bok-Ghee, additional, Havulinna, Aki S., additional, Hayward, Caroline, additional, Hernandez, Dena, additional, Hillege, Hans, additional, Ittermann, Till, additional, Kent, Jack W., additional, Kolcic, Ivana, additional, Laatikainen, Tiina, additional, Lahti, Jari, additional, Leach, Irene Mateo, additional, Lee, Christine G., additional, Lee, Jong-Young, additional, Liu, Tian, additional, Liu, Youfang, additional, Lobbens, Stéphane, additional, Loh, Marie, additional, Lyytikäinen, Leo-Pekka, additional, Medina-Gomez, Carolina, additional, Michaëlsson, Karl, additional, Nalls, Mike A., additional, Nielson, Carrie M., additional, Oozageer, Laticia, additional, Pascoe, Laura, additional, Paternoster, Lavinia, additional, Polašek, Ozren, additional, Ripatti, Samuli, additional, Sarzynski, Mark A., additional, Shin, Chan Soo, additional, Narančić, Nina Smolej, additional, Spira, Dominik, additional, Srikanth, Priya, additional, Steinhagen-Thiessen, Elisabeth, additional, Sung, Yun Ju, additional, Swart, Karin M. A., additional, Taittonen, Leena, additional, Tanaka, Toshiko, additional, Tikkanen, Emmi, additional, van der Velde, Nathalie, additional, van Schoor, Natasja M., additional, Verweij, Niek, additional, Wright, Alan F., additional, Yu, Lei, additional, Zmuda, Joseph M., additional, Eklund, Niina, additional, Forrester, Terrence, additional, Grarup, Niels, additional, Jackson, Anne U., additional, Kristiansson, Kati, additional, Kuulasmaa, Teemu, additional, Kuusisto, Johanna, additional, Lichtner, Peter, additional, Luan, Jian'an, additional, Mahajan, Anubha, additional, Männistö, Satu, additional, Palmer, Cameron D., additional, Ried, Janina S., additional, Scott, Robert A., additional, Stancáková, Alena, additional, Wagner, Peter J., additional, Demirkan, Ayse, additional, Döring, Angela, additional, Gudnason, Vilmundur, additional, Kiel, Douglas P., additional, Kühnel, Brigitte, additional, Mangino, Massimo, additional, Mcknight, Barbara, additional, Menni, Cristina, additional, O'Connell, Jeffrey R., additional, Oostra, Ben A., additional, Shuldiner, Alan R., additional, Song, Kijoung, additional, Vandenput, Liesbeth, additional, van Duijn, Cornelia M., additional, Vollenweider, Peter, additional, White, Charles C., additional, Boehnke, Michael, additional, Boettcher, Yvonne, additional, Cooper, Richard S., additional, Forouhi, Nita G., additional, Gieger, Christian, additional, Grallert, Harald, additional, Hingorani, Aroon, additional, Jørgensen, Torben, additional, Jousilahti, Pekka, additional, Kivimaki, Mika, additional, Kumari, Meena, additional, Laakso, Markku, additional, Langenberg, Claudia, additional, Linneberg, Allan, additional, Luke, Amy, additional, Mckenzie, Colin A., additional, Palotie, Aarno, additional, Pedersen, Oluf, additional, Peters, Annette, additional, Strauch, Konstantin, additional, Tayo, Bamidele O., additional, Wareham, Nicholas J., additional, Bennett, David A., additional, Bertram, Lars, additional, Blangero, John, additional, Blüher, Matthias, additional, Bouchard, Claude, additional, Campbell, Harry, additional, Cho, Nam H., additional, Cummings, Steven R., additional, Czerwinski, Stefan A., additional, Demuth, Ilja, additional, Eckardt, Rahel, additional, Eriksson, Johan G., additional, Ferrucci, Luigi, additional, Franco, Oscar H., additional, Froguel, Philippe, additional, Gansevoort, Ron T., additional, Hansen, Torben, additional, Harris, Tamara B., additional, Hastie, Nicholas, additional, Heliövaara, Markku, additional, Hofman, Albert, additional, Jordan, Joanne M., additional, Jula, Antti, additional, Kähönen, Mika, additional, Kajantie, Eero, additional, Knekt, Paul B., additional, Koskinen, Seppo, additional, Kovacs, Peter, additional, Lehtimäki, Terho, additional, Lind, Lars, additional, Liu, Yongmei, additional, Orwoll, Eric S., additional, Osmond, Clive, additional, Perola, Markus, additional, Pérusse, Louis, additional, Raitakari, Olli T., additional, Rankinen, Tuomo, additional, Rao, D. C., additional, Rice, Treva K., additional, Rivadeneira, Fernando, additional, Rudan, Igor, additional, Salomaa, Veikko, additional, Sørensen, Thorkild I. A., additional, Stumvoll, Michael, additional, Tönjes, Anke, additional, Towne, Bradford, additional, Tranah, Gregory J., additional, Tremblay, Angelo, additional, Uitterlinden, André G., additional, van der Harst, Pim, additional, Vartiainen, Erkki, additional, Viikari, Jorma S., additional, Vitart, Veronique, additional, Vohl, Marie-Claude, additional, Völzke, Henry, additional, Walker, Mark, additional, Wallaschofski, Henri, additional, Wild, Sarah, additional, Wilson, James F., additional, Yengo, Loïc, additional, Bishop, D. Timothy, additional, Borecki, Ingrid B., additional, Chambers, John C., additional, Cupples, L. Adrienne, additional, Dehghan, Abbas, additional, Deloukas, Panos, additional, Fatemifar, Ghazaleh, additional, Fox, Caroline, additional, Furey, Terrence S., additional, Franke, Lude, additional, Han, Jiali, additional, Hunter, David J., additional, Karjalainen, Juha, additional, Karpe, Fredrik, additional, Kaplan, Robert C., additional, Kooner, Jaspal S., additional, McCarthy, Mark I., additional, Murabito, Joanne M., additional, Morris, Andrew P., additional, Bishop, Julia A. N., additional, North, Kari E., additional, Ohlsson, Claes, additional, Ong, Ken K., additional, Prokopenko, Inga, additional, Richards, J. Brent, additional, Schadt, Eric E., additional, Spector, Tim D., additional, Widén, Elisabeth, additional, Willer, Cristen J., additional, Yang, Jian, additional, Ingelsson, Erik, additional, Mohlke, Karen L., additional, Hirschhorn, Joel N., additional, Pospisilik, John Andrew, additional, Zillikens, M. Carola, additional, Lindgren, Cecilia, additional, Kilpeläinen, Tuomas Oskari, additional, and Loos, Ruth J. F., additional

Published
2016
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43. The value of postoperative anticoagulants to improve flap survival in the free radial forearm flap: A systematic review and retrospective multicenter analysis.

Author

MS KNO, Brain, Zorgeenheid KNO Medisch, Other research (not in main researchprogram), Swartz, Justin E., Aarts, Mark, Swart, Karin M A, Disa, Joseph J, Gerressen, Marcus, Kuo, Yur Ren, Wax, Mark K, Grolman, Wilko, Braunius, Weibel W, MS KNO, Brain, Zorgeenheid KNO Medisch, Other research (not in main researchprogram), Swartz, Justin E., Aarts, Mark, Swart, Karin M A, Disa, Joseph J, Gerressen, Marcus, Kuo, Yur Ren, Wax, Mark K, Grolman, Wilko, and Braunius, Weibel W

Published
2015

45. Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium

Author

Moayyeri, Alireza, Hsu, Yi-Hsiang, Karasik, David, Estrada, Karol, Xiao, Su-Mei, Nielson, Carrie, Srikanth, Priya, Giroux, Sylvie, Wilson, Scott G., Zheng, Hou-Feng, Smith, Albert V., Pye, Stephen R., Leo, Paul J., Teumer, Alexander, Hwang, Joo-Yeon, Ohlsson, Claes, McGuigan, Fiona, Minster, Ryan L., Hayward, Caroline, Olmos, Jose M., Lyytikaeinen, Leo-Pekka, Lewis, Joshua R., Swart, Karin M. A., Masi, Laura, Oldmeadow, Chris, Holliday, Elizabeth G., Cheng, Sulin, van Schoor, Natasja M., Harvey, Nicholas C., Kruk, Marcin, Fabiola Del Greco, M., Igl, Wilmar, Trummer, Olivia, Grigoriou, Efi, Luben, Robert, Liu, Ching-Ti, Zhou, Yanhua, Oei, Ling, Medina-Gomez, Carolina, Zmuda, Joseph, Tranah, Greg, Brown, Suzanne J., Williams, Frances M., Soranzo, Nicole, Jakobsdottir, Johanna, Siggeirsdottir, Kristin, Holliday, Kate L., Hannemann, Anke, Go, Min Jin, Garcia, Melissa, Polasek, Ozren, Laaksonen, Marika, Zhu, Kun, Enneman, Anke W., McEvoy, Mark, Peel, Roseanne, Sham, Pak Chung, Jaworski, Maciej, Johansson, Asa, Hicks, Andrew A., Pludowski, Pawel, Scott, Rodney, Dhonukshe-Rutten, Rosalie A. M., van der Velde, Nathalie, Kaehoenen, Mika, Viikari, Jorma S., Sievaenen, Harri, Raitakari, Olli T., Gonzalez-Macias, Jesus, Hernandez, Jose L., Mellstroem, Dan, Ljunggren, Östen, Cho, Yoon Shin, Voelker, Uwe, Nauck, Matthias, Homuth, Georg, Voelzke, Henry, Haring, Robin, Brown, Matthew A., McCloskey, Eugene, Nicholson, Geoffrey C., Eastell, Richard, Eisman, John A., Jones, Graeme, Reid, Ian R., Dennison, Elaine M., Wark, John, Boonen, Steven, Vanderschueren, Dirk, Wu, Frederick C. W., Aspelund, Thor, Richards, J. Brent, Bauer, Doug, Hofman, Albert, Khaw, Kay-Tee, Dedoussis, George, Obermayer-Pietsch, Barbara, Gyllensten, Ulf, Pramstaller, Peter P., Lorenc, Roman S., Cooper, Cyrus, Kung, Annie Wai Chee, Lips, Paul, Alen, Markku, Attia, John, Luisa Brandi, Maria, de Groot, Lisette C. P. G. M., Lehtimaeki, Terho, Riancho, Jose A., Campbell, Harry, Liu, Yongmei, Harris, Tamara B., Akesson, Kristina, Karlsson, Magnus, Lee, Jong-Young, Wallaschofski, Henri, Duncan, Emma L., O'Neill, Terence W., Gudnason, Vilmundur, Spector, Timothy D., Rousseau, Francois, Orwoll, Eric, Cummings, Steven R., Wareham, Nick J., Rivadeneira, Fernando, Uitterlinden, Andre G., Prince, Richard L., Kiel, Douglas P., Reeve, Jonathan, Kaptoge, Stephen K., Moayyeri, Alireza, Hsu, Yi-Hsiang, Karasik, David, Estrada, Karol, Xiao, Su-Mei, Nielson, Carrie, Srikanth, Priya, Giroux, Sylvie, Wilson, Scott G., Zheng, Hou-Feng, Smith, Albert V., Pye, Stephen R., Leo, Paul J., Teumer, Alexander, Hwang, Joo-Yeon, Ohlsson, Claes, McGuigan, Fiona, Minster, Ryan L., Hayward, Caroline, Olmos, Jose M., Lyytikaeinen, Leo-Pekka, Lewis, Joshua R., Swart, Karin M. A., Masi, Laura, Oldmeadow, Chris, Holliday, Elizabeth G., Cheng, Sulin, van Schoor, Natasja M., Harvey, Nicholas C., Kruk, Marcin, Fabiola Del Greco, M., Igl, Wilmar, Trummer, Olivia, Grigoriou, Efi, Luben, Robert, Liu, Ching-Ti, Zhou, Yanhua, Oei, Ling, Medina-Gomez, Carolina, Zmuda, Joseph, Tranah, Greg, Brown, Suzanne J., Williams, Frances M., Soranzo, Nicole, Jakobsdottir, Johanna, Siggeirsdottir, Kristin, Holliday, Kate L., Hannemann, Anke, Go, Min Jin, Garcia, Melissa, Polasek, Ozren, Laaksonen, Marika, Zhu, Kun, Enneman, Anke W., McEvoy, Mark, Peel, Roseanne, Sham, Pak Chung, Jaworski, Maciej, Johansson, Asa, Hicks, Andrew A., Pludowski, Pawel, Scott, Rodney, Dhonukshe-Rutten, Rosalie A. M., van der Velde, Nathalie, Kaehoenen, Mika, Viikari, Jorma S., Sievaenen, Harri, Raitakari, Olli T., Gonzalez-Macias, Jesus, Hernandez, Jose L., Mellstroem, Dan, Ljunggren, Östen, Cho, Yoon Shin, Voelker, Uwe, Nauck, Matthias, Homuth, Georg, Voelzke, Henry, Haring, Robin, Brown, Matthew A., McCloskey, Eugene, Nicholson, Geoffrey C., Eastell, Richard, Eisman, John A., Jones, Graeme, Reid, Ian R., Dennison, Elaine M., Wark, John, Boonen, Steven, Vanderschueren, Dirk, Wu, Frederick C. W., Aspelund, Thor, Richards, J. Brent, Bauer, Doug, Hofman, Albert, Khaw, Kay-Tee, Dedoussis, George, Obermayer-Pietsch, Barbara, Gyllensten, Ulf, Pramstaller, Peter P., Lorenc, Roman S., Cooper, Cyrus, Kung, Annie Wai Chee, Lips, Paul, Alen, Markku, Attia, John, Luisa Brandi, Maria, de Groot, Lisette C. P. G. M., Lehtimaeki, Terho, Riancho, Jose A., Campbell, Harry, Liu, Yongmei, Harris, Tamara B., Akesson, Kristina, Karlsson, Magnus, Lee, Jong-Young, Wallaschofski, Henri, Duncan, Emma L., O'Neill, Terence W., Gudnason, Vilmundur, Spector, Timothy D., Rousseau, Francois, Orwoll, Eric, Cummings, Steven R., Wareham, Nick J., Rivadeneira, Fernando, Uitterlinden, Andre G., Prince, Richard L., Kiel, Douglas P., Reeve, Jonathan, and Kaptoge, Stephen K.

Abstract

Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

Published
2014
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46. Folate and Vitamin B12-Related Biomarkers in Relation to Brain Volumes.

Author

van der Zwaluw, Nikita L., Brouwer-Brolsma, Elske M., van de Rest, Ondine, van Wijngaarden, Janneke P., In't Veld, Paulette H., Kourie, Daniella I., Kok, Frans J., Dhonukshe-Rutten, Rosalie A. M., de Groot, Lisette C. P. G. M., Smeets, Paul A. M., Swart, Karin M. A., Enneman, Anke W., van Dijk, Suzanne C., van der Velde, Nathalie, and Kessels, Roy P. C.

Abstract

Aim: We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B12 status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin Bi2 supplementation with participants who did not. Methods: Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B12, or a placebo. After two years of intervention, T1-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B12, holotranscobalamin, and methylmalonic acid concentrations were measured. Results: Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = -0.91, 95% CI -1.85-0.03; p = 0.06) and between serum folate and TBV (β = -0.20, 95% CI -0.38, -0.02; p = 0.03). No significant associations were observed for serum vitamin B12 and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064,95% CI 1058-1069 mL) than the non-supplemented group (1072, 95% CI 1067-1078 mL, p = 0.03). Conclusions: Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B12 supplementation will be beneficial above and beyond normal dietary intake for brain health. [ABSTRACT FROM AUTHOR]

Published
2017
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47. Effects of Two-Year Vitamin B12 and Folic Acid Supplementation on Depressive Symptoms and Quality of Life in Older Adults with Elevated Homocysteine Concentrations: Additional Results from the B-PROOF Study, an RCT.

Author

de Koning, Elisa J., van der Zwaluw, Nikita L., van Wijngaarden, Janneke P., Sohl, Evelien, Brouwer-Brolsma, Elske M., van Marwijk, Harm W. J., Enneman, Anke W., Swart, Karin M. A., van Dijk, Suzanne C., Ham, Annelies C., van der Velde, Nathalie, Uitterlinden, André G., Penninx, Brenda W. J. H., Elders, Petra J. M., Lips, Paul, Dhonukshe-Rutten, Rosalie A. M., van Schoor, Natasja M., and de Groot, Lisette C. P. G. M.

Abstract

Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B12 and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants (N = 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) received either 500 µg vitamin B12 and 400 µg folic acid daily or placebo for two years. Both tablets contained 15 µg vitamin D3. Depressive symptoms were measured with the Geriatric Depression Scale-15 (GDS-15). HR-QoL was assessed with the SF-12 Mental and Physical component summary scores and the EQ-5D Index score and Visual Analogue Scale. Differences in two-year change scores were analyzed with Analysis of Covariance (ANCOVA). Hcy concentrations decreased more in the intervention group, but two-year change scores of the GDS-15 and three of four HR-QoL measures did not differ between groups. The EQ-5D Index score declined less in the intervention group than in the placebo group (mean change 0.00 vs. -0.02, p = 0.004). In conclusion, two-year supplementation with vitamin B12 and folic acid in older adults with hyperhomocysteinemia showed that lowering Hcy concentrations does not reduce depressive symptoms, but it may have a small positive effect on HR-QoL. [ABSTRACT FROM AUTHOR]

Published
2016
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48. Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia.

Author

van Dijk, Suzanne C., Enneman, Anke W., Swart, Karin M. A., van Wijngaarden, Janneke P., Ham, Annelies C., de Jonge, R., Blom, Henk J., Feskens, Edith J., Geleijnse, Johanna Marianne, van Schoor, Natasja M., Dhonukshe-Rutten, Rosalie A. M., de Jongh, Renate T., Lips, Paul, de Groot, Lisette C. P. G. M., Uitterlinden, Andre G., van den Meiracker, Ton H., Mattace-Raso, Francesco U. S., van der Velde, Nathalie, and Smulders, Yvo M.

Subjects
HYPERHOMOCYSTEINEMIA, ENDOTHELIUM diseases, AMYLOID, VITAMINS, AMINO acid metabolism disorders
Abstract

B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (–1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514 [ABSTRACT FROM AUTHOR]

Published
2016
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49. Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial.

Author

van Wijngaarden, Janneke P., Swart, Karin M. A., Enneman, Anke W., Dhonukshe-Rutten, Rosalie A. M., van Dijk, Suzanne C., Ham, Annelies C., Brouwer-Brolsma, Elske M., van der Zwaluw, Nikita L., Sohl, Evelien, van Meurs, Joyce B. J., Zillikens, M. Carola, van Schoor, Natasja M., van der Velde, Nathalie, Brug, Johannes, Uitterlinden, André G., Lips, Paul, and de Groot, Lisette C. P. G. M.

Subjects
BONE fracture prevention, GERIATRIC nutrition, ANTHROPOMETRY, CHI-squared test, CONFIDENCE intervals, CONGREGATE housing, DIETARY supplements, FOLIC acid, LONGITUDINAL method, OSTEOPOROSIS, PROBABILITY theory, RESEARCH funding, STATISTICAL sampling, T-test (Statistics), VITAMIN B12, HOMOCYSTEINE, RANDOMIZED controlled trials, PRE-tests & post-tests, INDEPENDENT living, PROPORTIONAL hazards models, BLIND experiment, DATA analysis software, HYPERHOMOCYSTEINEMIA, DESCRIPTIVE statistics, KAPLAN-Meier estimator, LOG-rank test, ODDS ratio, GENOTYPES, DISEASE complications, OLD age
Abstract

Background: Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures. Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce fracture risk. Objective: This study [B-vitamins for the PRevention Of Osteoporotic Fractures (B-PROOF)] aimed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals. Design: This was a double-blind, randomized, placebo-controlled trial in 2919 participants aged ≥65 y with elevated homocysteine concentrations (12-50 µmol/L). Participants were assigned to receive daily 500 µg vitamin B-12 plus 400 μg folic acid or placebo supplementation for 2 y. Both intervention and placebo tablets also contained 600 IU vitamin D3. The primary endpoint was time to first osteoporotic fracture. Exploratory prespecified subgroup analyses were performed in men and women and in individuals younger than and older than age 80 y. Data were analyzed according to intention-to-treat and per-protocol principles. Results: Osteoporotic fractures occurred in 61 persons (4.2%) in the intervention group and 75 persons (5.1%) in the placebo group. Osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses (HR: 0.84; 95% CI: 0.58, 1.21) or per-protocol analyses (HR: 0.81; 95% CI: 0.54, 1.21). For persons >80 y, in per-protocol analyses, osteoporotic fracture risk was lower in the intervention group than in the placebo group (HR: 0.27; 95% CI: 0.10, 0.74). The total number of adverse events (including mortality) did not differ between groups. However, 63 and 42 participants in the intervention and placebo groups, respectively, reported incident cancer (HR: 1.56; 95% CI: 1.04, 2.31). Conclusions: These data show that combined vitamin B-12 and folic acid supplementation had no effect on osteoporotic fracture incidence in this elderly population. Exploratory subgroup analyses suggest a beneficial effect on osteoporotic fracture prevention in compliant persons aged >80 y. However, treatment was also associated with increased incidence of cancer, although the study was not designed for assessing cancer outcomes. Therefore, vitamin B-12 plus folic acid supplementation cannot be recommended at present for fracture prevention in elderly people. The B-PROOF study was registered with the Netherlands Trial Register (trialregister.nl) as NTR1333 and at clinicaltrials.gov as NCT00696414. [ABSTRACT FROM AUTHOR]

Published
2014
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50. Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence.

Author

van Wijngaarden, Janneke P, Dhonukshe-Rutten, Rosalie A M, van Schoor, Natasja M, van der Velde, Nathalie, Swart, Karin M A, Enneman, Anke W, van Dijk, Suzanne C, Brouwer-Brolsma, Elske M, Zillikens, M Carola, van Meurs, Joyce B J, Brug, Johannes, Uitterlinden, André G, Lips, Paul, and de Groot, Lisette C P G M

Abstract

Background: Osteoporosis is a major health problem, and the economic burden is expected to rise due to an increase in life expectancy throughout the world. Current observational evidence suggests that an elevated homocysteine concentration and poor vitamin B12 and folate status are associated with an increased fracture risk. As vitamin B12 and folate intake and status play a large role in homocysteine metabolism, it is hypothesized that supplementation with these B-vitamins will reduce fracture incidence in elderly people with an elevated homocysteine concentration.Methods/design: The B-PROOF (B-Vitamins for the PRevention Of Osteoporotic Fractures) study is a randomized double-blind placebo-controlled trial. The intervention comprises a period of two years, and includes 2919 subjects, aged 65 years and older, independently living or institutionalized, with an elevated homocysteine concentration (≥ 12 μmol/L). One group receives daily a tablet with 500 μg vitamin B12 and 400 μg folic acid and the other group receives a placebo tablet. In both tablets 15 μg (600 IU) vitamin D is included. The primary outcome of the study is osteoporotic fractures. Measurements are performed at baseline and after two years and cover bone health i.e. bone mineral density and bone turnover markers, physical performance and physical activity including falls, nutritional intake and status, cognitive function, depression, genetics and quality of life. This large multi-center project is carried out by a consortium from the Erasmus MC (Rotterdam, the Netherlands), VUmc (Amsterdam, the Netherlands) and Wageningen University, (Wageningen, the Netherlands), the latter acting as coordinator.Discussion: To our best knowledge, the B-PROOF study is the first intervention study in which the effect of vitamin B12 and folic acid supplementation on osteoporotic fractures is studied in a general elderly population. We expect the first longitudinal results of the B-PROOF intervention in the second semester of 2013. The results of this intervention will provide evidence on the efficacy of vitamin B12 and folate supplementation in the prevention of osteoporotic fractures.Trial Registration: The B-PROOF study is registered with the Netherlands Trial (NTR NTR1333) and with ClinicalTrials.gov (NCT00696514). [ABSTRACT FROM AUTHOR]

Published
2011
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