Search

Your search keyword '"Den Hoed, Marcel"' showing total 181 results
Start Over Author "Den Hoed, Marcel"
181 results on '"Den Hoed, Marcel"'

1. Genetic insights into resting heart rate and its role in cardiovascular disease.

Author

van de Vegte, Yordi, Eppinga, Ruben, van der Ende, M, Hagemeijer, Yanick, Mahendran, Yuvaraj, Salfati, Elias, Smith, Albert, Tan, Vanessa, Arking, Dan, Ntalla, Ioanna, Appel, Emil, Schurmann, Claudia, Brody, Jennifer, Rueedi, Rico, Polasek, Ozren, Sveinbjornsson, Gardar, Lecoeur, Cecile, Ladenvall, Claes, Zhao, Jing, Isaacs, Aaron, Wang, Lihua, Luan, Jianan, Hwang, Shih-Jen, Mononen, Nina, Auro, Kirsi, Jackson, Anne, Bielak, Lawrence, Zeng, Linyao, Shah, Nabi, Nethander, Maria, Campbell, Archie, Rankinen, Tuomo, Pechlivanis, Sonali, Qi, Lu, Zhao, Wei, Rizzi, Federica, Tanaka, Toshiko, Robino, Antonietta, Cocca, Massimiliano, Lange, Leslie, Müller-Nurasyid, Martina, Roselli, Carolina, Zhang, Weihua, Kleber, Marcus, Guo, Xiuqing, Lin, Henry, Pavani, Francesca, Galesloot, Tessel, Noordam, Raymond, Milaneschi, Yuri, Schraut, Katharina, den Hoed, Marcel, Degenhardt, Frauke, Trompet, Stella, van den Berg, Marten, Pistis, Giorgio, Tham, Yih-Chung, Weiss, Stefan, Sim, Xueling, Li, Hengtong, van der Most, Peter, Nolte, Ilja, Lyytikäinen, Leo-Pekka, Said, M, Witte, Daniel, Iribarren, Carlos, Launer, Lenore, Ring, Susan, de Vries, Paul, Sever, Peter, Linneberg, Allan, Bottinger, Erwin, Padmanabhan, Sandosh, Psaty, Bruce, Sotoodehnia, Nona, Kolcic, Ivana, Arnar, David, Gudbjartsson, Daniel, Holm, Hilma, Balkau, Beverley, Silva, Claudia, Newton-Cheh, Christopher, Nikus, Kjell, Salo, Perttu, Mohlke, Karen, Peyser, Patricia, Schunkert, Heribert, Lorentzon, Mattias, Lahti, Jari, Rao, Dabeeru, Cornelis, Marilyn, Faul, Jessica, Smith, Jennifer, Stolarz-Skrzypek, Katarzyna, Bandinelli, Stefania, Concas, Maria, Sinagra, Gianfranco, Meitinger, Thomas, Waldenberger, Melanie, and Sinner, Moritz

Subjects
Humans, Cardiovascular Diseases, Risk Factors, Heart Rate, Genetic Predisposition to Disease, Atrial Fibrillation, Mendelian Randomization Analysis, Genome-Wide Association Study, Polymorphism, Single Nucleotide
Abstract

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

Published
2023

2. GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification

Author

Lagou, Vasiliki, Jiang, Longda, Ulrich, Anna, Zudina, Liudmila, González, Karla Sofia Gutiérrez, Balkhiyarova, Zhanna, Faggian, Alessia, Maina, Jared G., Chen, Shiqian, Todorov, Petar V., Sharapov, Sodbo, David, Alessia, Marullo, Letizia, Mägi, Reedik, Rujan, Roxana-Maria, Ahlqvist, Emma, Thorleifsson, Gudmar, Gao, Ηe, Εvangelou, Εvangelos, Benyamin, Beben, Scott, Robert A., Isaacs, Aaron, Zhao, Jing Hua, Willems, Sara M., Johnson, Toby, Gieger, Christian, Grallert, Harald, Meisinger, Christa, Müller-Nurasyid, Martina, Strawbridge, Rona J., Goel, Anuj, Rybin, Denis, Albrecht, Eva, Jackson, Anne U., Stringham, Heather M., Corrêa, Jr., Ivan R., Farber-Eger, Eric, Steinthorsdottir, Valgerdur, Uitterlinden, André G., Munroe, Patricia B., Brown, Morris J., Schmidberger, Julian, Holmen, Oddgeir, Thorand, Barbara, Hveem, Kristian, Wilsgaard, Tom, Mohlke, Karen L., Wang, Zhe, Shmeliov, Aleksey, den Hoed, Marcel, Loos, Ruth J. F., Kratzer, Wolfgang, Haenle, Mark, Koenig, Wolfgang, Boehm, Bernhard O., Tan, Tricia M., Tomas, Alejandra, Salem, Victoria, Barroso, Inês, Tuomilehto, Jaakko, Boehnke, Michael, Florez, Jose C., Hamsten, Anders, Watkins, Hugh, Njølstad, Inger, Wichmann, H.-Erich, Caulfield, Mark J., Khaw, Kay-Tee, van Duijn, Cornelia M., Hofman, Albert, Wareham, Nicholas J., Langenberg, Claudia, Whitfield, John B., Martin, Nicholas G., Montgomery, Grant, Scapoli, Chiara, Tzoulaki, Ioanna, Elliott, Paul, Thorsteinsdottir, Unnur, Stefansson, Kari, Brittain, Evan L., McCarthy, Mark I., Froguel, Philippe, Sexton, Patrick M., Wootten, Denise, Groop, Leif, Dupuis, Josée, Meigs, James B., Deganutti, Giuseppe, Demirkan, Ayse, Pers, Tune H., Reynolds, Christopher A., Aulchenko, Yurii S., Kaakinen, Marika A., Jones, Ben, and Prokopenko, Inga

Published
2023
Full Text
View/download PDF

4. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Author

Mathieson, Iain, Day, Felix R., Barban, Nicola, Tropf, Felix C., Brazel, David M., Vaez, Ahmad, van Zuydam, Natalie, Bitarello, Bárbara D., Gardner, Eugene J., Akimova, Evelina T., Azad, Ajuna, Bergmann, Sven, Bielak, Lawrence F., Boomsma, Dorret I., Bosak, Kristina, Brumat, Marco, Buring, Julie E., Cesarini, David, Chasman, Daniel I., Chavarro, Jorge E., Cocca, Massimiliano, Concas, Maria Pina, Davey Smith, George, Davies, Gail, Deary, Ian J., Esko, Tõnu, Faul, Jessica D., Franco, Oscar, Ganna, Andrea, Gaskins, Audrey J., Gelemanovic, Andrea, de Geus, Eco J. C., Gieger, Christian, Girotto, Giorgia, Gopinath, Bamini, Grabe, Hans Jörgen, Gunderson, Erica P., Hayward, Caroline, He, Chunyan, van Heemst, Diana, Hill, W. David, Hoffmann, Eva R., Homuth, Georg, Hottenga, Jouke Jan, Huang, Hongyang, Hyppӧnen, Elina, Ikram, M. Arfan, Jansen, Rick, Johannesson, Magnus, Kamali, Zoha, Kardia, Sharon L. R., Kavousi, Maryam, Kifley, Annette, Kiiskinen, Tuomo, Kraft, Peter, Kühnel, Brigitte, Langenberg, Claudia, Liew, Gerald, Lind, Penelope A., Luan, Jian’an, Mägi, Reedik, Magnusson, Patrik K. E., Mahajan, Anubha, Martin, Nicholas G., Mbarek, Hamdi, McCarthy, Mark I., McMahon, George, Medland, Sarah E., Meitinger, Thomas, Metspalu, Andres, Mihailov, Evelin, Milani, Lili, Missmer, Stacey A., Mitchell, Paul, Møllegaard, Stine, Mook-Kanamori, Dennis O., Morgan, Anna, van der Most, Peter J., de Mutsert, Renée, Nauck, Matthias, Nolte, Ilja M., Noordam, Raymond, Penninx, Brenda W. J. H., Peters, Annette, Peyser, Patricia A., Polašek, Ozren, Power, Chris, Pribisalic, Ajka, Redmond, Paul, Rich-Edwards, Janet W., Ridker, Paul M., Rietveld, Cornelius A., Ring, Susan M., Rose, Lynda M., Rueedi, Rico, Shukla, Vallari, Smith, Jennifer A., Stankovic, Stasa, Stefánsson, Kári, Stöckl, Doris, Strauch, Konstantin, Swertz, Morris A., Teumer, Alexander, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Thurik, A. Roy, Timpson, Nicholas J., Turman, Constance, Uitterlinden, André G., Waldenberger, Melanie, Wareham, Nicholas J., Weir, David R., Willemsen, Gonneke, Zhao, Jing Hau, Zhao, Wei, Zhao, Yajie, Snieder, Harold, den Hoed, Marcel, Ong, Ken K., Mills, Melinda C., and Perry, John R. B.

Published
2023
Full Text
View/download PDF

5. Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression

Author

Mattis, Katia K., Krentz, Nicole A. J., Metzendorf, Christoph, Abaitua, Fernando, Spigelman, Aliya F., Sun, Han, Ikle, Jennifer M., Thaman, Swaraj, Rottner, Antje K., Bautista, Austin, Mazzaferro, Eugenia, Perez-Alcantara, Marta, Manning Fox, Jocelyn E., Torres, Jason M., Wesolowska-Andersen, Agata, Yu, Grace Z., Mahajan, Anubha, Larsson, Anders, MacDonald, Patrick E., Davies, Benjamin, den Hoed, Marcel, and Gloyn, Anna L.

Published
2023
Full Text
View/download PDF

6. Multi‐phenotype analyses of hemostatic traits with cardiovascular events reveal novel genetic associations

Author

Temprano‐Sagrera, Gerard, Sitlani, Colleen M., Bone, William P., Martin‐Bornez, Miguel, Voight, Benjamin F., Morrison, Alanna C., Damrauer, Scott M., de Vries, Paul S., Smith, Nicholas L., Sabater‐Lleal, Maria, Dehghan, Abbas, Heath, Adam S, Morrison, Alanna C, Reiner, Alex P, Johnson, Andrew, Richmond, Anne, Peters, Annette, van Hylckama Vlieg, Astrid, McKnight, Barbara, Psaty, Bruce M, Hayward, Caroline, Ward‐Caviness, Cavin, O’Donnell, Christopher, Chasman, Daniel, Strachan, David P, Tregouet, David A, Mook‐Kanamori, Dennis, Gill, Dipender, Thibord, Florian, Asselbergs, Folkert W, Leebeek, Frank W.G., Rosendaal, Frits R, Davies, Gail, Homuth, Georg, Temprano, Gerard, Campbell, Harry, Taylor, Herman A, Bressler, Jan, Huffman, Jennifer E, Rotter, Jerome I, Yao, Jie, Wilson, James F, Bis, Joshua C, Hahn, Julie M, Desch, Karl C, Wiggins, Kerri L, Raffield, Laura M, Bielak, Lawrence F, Yanek, Lisa R, Kleber, Marcus E, Mueller, Martina, Kavousi, Maryam, Mangino, Massimo, Liu, Melissa, Brown, Michael R, Conomos, Matthew P, Jhun, Min‐A, Chen, Ming‐Huei, de Maat, Moniek P.M., Pankratz, Nathan, Smith, Nicholas L, Peyser, Patricia A, Elliot, Paul, de Vries, Paul S, Wei, Peng, Wild, Philipp S, Morange, Pierre E, van der Harst, Pim, Yang, Qiong, Le, Ngoc‐Quynh, Marioni, Riccardo, Li, Ruifang, Damrauer, Scott M, Cox, Simon R, Trompet, Stella, Felix, Stephan B, Völker, Uwe, Tang, Weihong, Koenig, Wolfgang, Jukema, J. Wouter, Guo, Xiuqing, Lindstrom, Sara, Wang, Lu, Smith, Erin N, Gordon, William, de Andrade, Mariza, Brody, Jennifer A, Pattee, Jack W, Haessler, Jeffrey, Brumpton, Ben M, Chasman, Daniel I, Suchon, Pierre, Turman, Constance, Germain, Marine, MacDonald, James, Braekkan, Sigrid K, Armasu, Sebastian M, Jackson, Rabecca D, Nielsen, Jonas B, Giulianini, Franco, Puurunen, Marja K, Ibrahim, Manal, Heckbert, Susan R, Bammler, Theo K, Frazer, Kelly A, McCauley, Bryan M, Taylor, Kent, Pankow, James S, Reiner, Alexander P, Gabrielsen, Maiken E, Deleuze, Jean‐François, O’Donnell, Chris J, Kim, Jihye, Kraft, Peter, Hansen, John‐Bjarne, Heit, John A, Kooperberg, Charles, Hveem, Kristian, Ridker, Paul M, Morange, Pierre‐Emmanuel, Johnson, Andrew D, Kabrhel, Christopher, Trégouët, David‐Alexandre, Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten‐Jacobs, Loes, Giese, Anne‐Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chen, Wei‐Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Holliday, Elizabeth G, Howard, George, Hsu, Fang‐Chi, Hyacinth, Hyacinth I, Arfan Ikram, M, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez‐Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin‐Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei‐Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Pulit, Sara L, Rannikmäe, Kristiina, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Rost, Natalia S, Rothwell, Peter M, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie LM, Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D, Thijs, Vincent NS, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Wassertheil‐Smoller, Sylvia, Wilson, James G, Yusuf, Salim, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu‐Ching, Hoan Choi, Seung, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean‐François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Mei Liu, Yong, Lopez, Oscar L, Makoto, Hirata, Martinez‐Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller‐Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Reddy Peddareddygari, Leema, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba‐Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti‐Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano‐Tárraga, Carolina, Stanne, Tara, Colin Stine, O, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres‐Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles DA, Wong, Quenna, Xu, Huichun, Yamaji, Taiki, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez‐Cadenas, Israel, Longstreth, W T, Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S, Howson, Joanna MM, Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2022
Full Text
View/download PDF

9. Biological/Genetic Regulation of Physical Activity Level

Author

Lightfoot, J Timothy, DE Geus, Eco JC, Booth, Frank W, Bray, Molly S, DEN Hoed, Marcel, Kaprio, Jaakko, Kelly, Scott A, Pomp, Daniel, Saul, Michael C, Thomis, Martine A, Garland, Theodore, and Bouchard, Claude

Subjects
Public Health, Health Sciences, Behavioral and Social Science, Genetics, Basic Behavioral and Social Science, Cancer, Good Health and Well Being, Biology, Consensus, Environment, Exercise, Health Behavior, Humans, Societies, Medical, Sports Medicine, ANIMAL, BIOLOGY, GENETICS, GENOMICS, HUMAN, PHYSICAL ACTIVITY, SPONTANEOUS ACTIVITY, VOLUNTARY PHYSICAL ACTIVITY, Human Movement and Sports Sciences, Medical Physiology, Public Health and Health Services, Sport Sciences, Clinical sciences, Medical physiology, Sports science and exercise
Abstract

PurposePhysical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity.ConclusionsFuture research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.

Published
2018

10. Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Anderson, Christopher D, Chong, Michael, Adams, Hieab HH, Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M, Benavente, Oscar R, Bevan, Steve, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chasman, Daniel I, Chen, Wei-Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul IW, DeStefano, Anita L, den Hoed, Marcel, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Heckbert, Susan R, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I, Ikram, M Arfan, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei-Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O’Donnell, Martin J, Psaty, Bruce M, Pulit, Sara L, Rannikmäe, Kristiina, Reiner, Alexander P, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Ridker, Paul M, Rost, Natalia S, Rothwell, Peter M, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, and Sale, Michele M

Subjects
Biological Sciences, Genetics, Human Genome, Stroke, Clinical Research, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Computational Biology, Databases, Genetic, Epigenesis, Genetic, Female, Gene Regulatory Networks, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, INDEL Mutation, Linkage Disequilibrium, Male, Models, Genetic, Polymorphism, Single Nucleotide, Risk Factors, AFGen Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, International Genomics of Blood Pressure (iGEN-BP) Consortium, INVENT Consortium, STARNET, BioBank Japan Cooperative Hospital Group, COMPASS Consortium, EPIC-CVD Consortium, EPIC-InterAct Consortium, International Stroke Genetics Consortium, METASTROKE Consortium, Neurology Working Group of the CHARGE Consortium, NINDS Stroke Genetics Network, UK Young Lacunar DNA Study, MEGASTROKE Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

Published
2018

11. PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Author

van Setten, Jessica, Brody, Jennifer A, Jamshidi, Yalda, Swenson, Brenton R, Butler, Anne M, Campbell, Harry, Del Greco, Fabiola M, Evans, Daniel S, Gibson, Quince, Gudbjartsson, Daniel F, Kerr, Kathleen F, Krijthe, Bouwe P, Lyytikäinen, Leo-Pekka, Müller, Christian, Müller-Nurasyid, Martina, Nolte, Ilja M, Padmanabhan, Sandosh, Ritchie, Marylyn D, Robino, Antonietta, Smith, Albert V, Steri, Maristella, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, Ulivi, Sheila, Verweij, Niek, Yin, Xiaoyan, Arnar, David O, Asselbergs, Folkert W, Bader, Joel S, Barnard, John, Bis, Josh, Blankenberg, Stefan, Boerwinkle, Eric, Bradford, Yuki, Buckley, Brendan M, Chung, Mina K, Crawford, Dana, den Hoed, Marcel, Denny, Josh C, Dominiczak, Anna F, Ehret, Georg B, Eijgelsheim, Mark, Ellinor, Patrick T, Felix, Stephan B, Franco, Oscar H, Franke, Lude, Harris, Tamara B, Holm, Hilma, Ilaria, Gandin, Iorio, Annamaria, Kähönen, Mika, Kolcic, Ivana, Kors, Jan A, Lakatta, Edward G, Launer, Lenore J, Lin, Honghuang, Lin, Henry J, Loos, Ruth JF, Lubitz, Steven A, Macfarlane, Peter W, Magnani, Jared W, Leach, Irene Mateo, Meitinger, Thomas, Mitchell, Braxton D, Munzel, Thomas, Papanicolaou, George J, Peters, Annette, Pfeufer, Arne, Pramstaller, Peter P, Raitakari, Olli T, Rotter, Jerome I, Rudan, Igor, Samani, Nilesh J, Schlessinger, David, Silva Aldana, Claudia T, Sinner, Moritz F, Smith, Jonathan D, Snieder, Harold, Soliman, Elsayed Z, Spector, Timothy D, Stott, David J, Strauch, Konstantin, Tarasov, Kirill V, Thorsteinsdottir, Unnur, Uitterlinden, Andre G, Van Wagoner, David R, Völker, Uwe, Völzke, Henry, Waldenberger, Melanie, Jan Westra, Harm, Wild, Philipp S, Zeller, Tanja, Alonso, Alvaro, Avery, Christy L, Bandinelli, Stefania, Benjamin, Emelia J, Cucca, Francesco, Dörr, Marcus, and Ferrucci, Luigi

Subjects
Biological Sciences, Genetics, Human Genome, Heart Disease, Biotechnology, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Atrial Function, Atrioventricular Node, Electrocardiography, Electrophysiological Phenomena, Female, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Mutation, Missense, Risk Factors
Abstract

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.

Published
2018

12. Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

Author

Graff, Mariaelisa, Scott, Robert A, Justice, Anne E, Young, Kristin L, Feitosa, Mary F, Barata, Llilda, Winkler, Thomas W, Chu, Audrey Y, Mahajan, Anubha, Hadley, David, Xue, Luting, Workalemahu, Tsegaselassie, Heard-Costa, Nancy L, den Hoed, Marcel, Ahluwalia, Tarunveer S, Qi, Qibin, Ngwa, Julius S, Renström, Frida, Quaye, Lydia, Eicher, John D, Hayes, James E, Cornelis, Marilyn, Kutalik, Zoltan, Lim, Elise, Luan, Jian'an, Huffman, Jennifer E, Zhang, Weihua, Zhao, Wei, Griffin, Paula J, Haller, Toomas, Ahmad, Shafqat, Marques-Vidal, Pedro M, Bien, Stephanie, Yengo, Loic, Teumer, Alexander, Smith, Albert Vernon, Kumari, Meena, Harder, Marie Neergaard, Justesen, Johanne Marie, Kleber, Marcus E, Hollensted, Mette, Lohman, Kurt, Rivera, Natalia V, Whitfield, John B, Zhao, Jing Hua, Stringham, Heather M, Lyytikäinen, Leo-Pekka, Huppertz, Charlotte, Willemsen, Gonneke, Peyrot, Wouter J, Wu, Ying, Kristiansson, Kati, Demirkan, Ayse, Fornage, Myriam, Hassinen, Maija, Bielak, Lawrence F, Cadby, Gemma, Tanaka, Toshiko, Mägi, Reedik, van der Most, Peter J, Jackson, Anne U, Bragg-Gresham, Jennifer L, Vitart, Veronique, Marten, Jonathan, Navarro, Pau, Bellis, Claire, Pasko, Dorota, Johansson, Åsa, Snitker, Søren, Cheng, Yu-Ching, Eriksson, Joel, Lim, Unhee, Aadahl, Mette, Adair, Linda S, Amin, Najaf, Balkau, Beverley, Auvinen, Juha, Beilby, John, Bergman, Richard N, Bergmann, Sven, Bertoni, Alain G, Blangero, John, Bonnefond, Amélie, Bonnycastle, Lori L, Borja, Judith B, Brage, Søren, Busonero, Fabio, Buyske, Steve, Campbell, Harry, Chines, Peter S, Collins, Francis S, Corre, Tanguy, Smith, George Davey, Delgado, Graciela E, Dueker, Nicole, Dörr, Marcus, Ebeling, Tapani, Eiriksdottir, Gudny, Esko, Tõnu, and Faul, Jessica D

Subjects
CHARGE Consortium, EPIC-InterAct Consortium, PAGE Consortium, Humans, Obesity, Genetic Predisposition to Disease, Body Mass Index, Waist-Hip Ratio, Exercise, Genotype, Female, Male, Adiposity, Waist Circumference, Genome-Wide Association Study, Epigenomics, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Genetics, Developmental Biology
Abstract

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

Published
2017

14. A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease.

Author

Scott, Robert A, Freitag, Daniel F, Li, Li, Chu, Audrey Y, Surendran, Praveen, Young, Robin, Grarup, Niels, Stancáková, Alena, Chen, Yuning, Varga, Tibor V, Yaghootkar, Hanieh, Luan, Jian'an, Zhao, Jing Hua, Willems, Sara M, Wessel, Jennifer, Wang, Shuai, Maruthur, Nisa, Michailidou, Kyriaki, Pirie, Ailith, van der Lee, Sven J, Gillson, Christopher, Al Olama, Ali Amin, Amouyel, Philippe, Arriola, Larraitz, Arveiler, Dominique, Aviles-Olmos, Iciar, Balkau, Beverley, Barricarte, Aurelio, Barroso, Inês, Garcia, Sara Benlloch, Bis, Joshua C, Blankenberg, Stefan, Boehnke, Michael, Boeing, Heiner, Boerwinkle, Eric, Borecki, Ingrid B, Bork-Jensen, Jette, Bowden, Sarah, Caldas, Carlos, Caslake, Muriel, CVD50 consortium, Cupples, L Adrienne, Cruchaga, Carlos, Czajkowski, Jacek, den Hoed, Marcel, Dunn, Janet A, Earl, Helena M, Ehret, Georg B, Ferrannini, Ele, Ferrieres, Jean, Foltynie, Thomas, Ford, Ian, Forouhi, Nita G, Gianfagna, Francesco, Gonzalez, Carlos, Grioni, Sara, Hiller, Louise, Jansson, Jan-Håkan, Jørgensen, Marit E, Jukema, J Wouter, Kaaks, Rudolf, Kee, Frank, Kerrison, Nicola D, Key, Timothy J, Kontto, Jukka, Kote-Jarai, Zsofia, Kraja, Aldi T, Kuulasmaa, Kari, Kuusisto, Johanna, Linneberg, Allan, Liu, Chunyu, Marenne, Gaëlle, Mohlke, Karen L, Morris, Andrew P, Muir, Kenneth, Müller-Nurasyid, Martina, Munroe, Patricia B, Navarro, Carmen, Nielsen, Sune F, Nilsson, Peter M, Nordestgaard, Børge G, Packard, Chris J, Palli, Domenico, Panico, Salvatore, Peloso, Gina M, Perola, Markus, Peters, Annette, Poole, Christopher J, Quirós, J Ramón, Rolandsson, Olov, Sacerdote, Carlotta, Salomaa, Veikko, Sánchez, María-José, Sattar, Naveed, Sharp, Stephen J, Sims, Rebecca, Slimani, Nadia, Smith, Jennifer A, Thompson, Deborah J, and Trompet, Stella

Subjects
CVD50 consortium, GERAD_EC Consortium, Neurology Working Group of the Cohorts for Heart, Aging Research in Genomic Epidemiology, Alzheimer’s Disease Genetics Consortium, Pancreatic Cancer Cohort Consortium, European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease, EPIC-InterAct, CHARGE consortium, CHD Exome+ Consortium, CARDIOGRAM Exome Consortium, Humans, Coronary Disease, Diabetes Mellitus, Type 2, Obesity, Receptor, Cannabinoid, CB2, Receptor, Serotonin, 5-HT2C, Receptors, Somatostatin, Genotype, Alleles, Sodium-Glucose Transporter 1, Dipeptidyl Peptidase 4, Glucagon-Like Peptide-1 Receptor, Medical and Health Sciences, Biological Sciences
Abstract

Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic therapies by predicting cardiovascular and other health endpoints. We therefore investigated the association of variants in six genes that encode drug targets for obesity or T2D with a range of metabolic traits in up to 11,806 individuals by targeted exome sequencing and follow-up in 39,979 individuals by targeted genotyping, with additional in silico follow-up in consortia. We used these data to first compare associations of variants in genes encoding drug targets with the effects of pharmacological manipulation of those targets in clinical trials. We then tested the association of those variants with disease outcomes, including coronary heart disease, to predict cardiovascular safety of these agents. A low-frequency missense variant (Ala316Thr; rs10305492) in the gene encoding glucagon-like peptide-1 receptor (GLP1R), the target of GLP1R agonists, was associated with lower fasting glucose and T2D risk, consistent with GLP1R agonist therapies. The minor allele was also associated with protection against heart disease, thus providing evidence that GLP1R agonists are not likely to be associated with an unacceptable increase in cardiovascular risk. Our results provide an encouraging signal that these agents may be associated with benefit, a question currently being addressed in randomized controlled trials. Genetic variants associated with metabolic traits and multiple disease outcomes can be used to validate therapeutic targets at an early stage in the drug development process.

Published
2016

20. Publisher Correction: Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W., Gretarsdottir, Solveig, Anderson, Christopher D., Chong, Michael, Adams, Hieab H. H., Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M., Benavente, Oscar R., Bevan, Steve, Boncoraglio, Giorgio B., Brown, Jr, Robert D., Butterworth, Adam S., Carrera, Caty, Carty, Cara L., Chasman, Daniel I., Chen, Wei-Min, Cole, John W., Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I. W., DeStefano, Anita L., den Hoed, Marcel, Duan, Qing, Engelter, Stefan T., Falcone, Guido J., Gottesman, Rebecca F., Grewal, Raji P., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B., Hassan, Ahamad, Havulinna, Aki S., Heckbert, Susan R., Holliday, Elizabeth G., Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I., Ikram, M. Arfan, Ingelsson, Erik, Irvin, Marguerite R., Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A., Jukema, J. Wouter, Kanai, Masahiro, Keene, Keith L., Kissela, Brett M., Kleindorfer, Dawn O., Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M., Lin, Wei-Yu, Lindgren, Arne G., Lorentzen, Erik, Magnusson, Patrik K., Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F., Meschia, James F., Mitchell, Braxton D., Mosley, Thomas H., Nalls, Michael A., Ninomiya, Toshiharu, O’Donnell, Martin J., Psaty, Bruce M., Pulit, Sara L., Rannikmäe, Kristiina, Reiner, Alexander P., Rexrode, Kathryn M., Rice, Kenneth, Rich, Stephen S., Ridker, Paul M., Rost, Natalia S., Rothwell, Peter M., Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Sakaue, Saori, Sale, Michele M., Salomaa, Veikko, Sapkota, Bishwa R., Schmidt, Reinhold, Schmidt, Carsten O., Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie L. M., Tanislav, Christian, Tatlisumak, Turgut, Taylor, Kent D., Thijs, Vincent N. S., Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M., Walters, Matthew, Wareham, Nicholas J., Wassertheil-Smoller, Sylvia, Wilson, James G., Wiggins, Kerri L., Yang, Qiong, Yusuf, Salim, AFGen Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, International Genomics of Blood Pressure (iGEN-BP) Consortium, INVENT Consortium, STARNET, Bis, Joshua C., Pastinen, Tomi, Ruusalepp, Arno, Schadt, Eric E., Koplev, Simon, Björkegren, Johan L. M., Codoni, Veronica, Civelek, Mete, Smith, Nicholas L., Trégouët, David A., Christophersen, Ingrid E., Roselli, Carolina, Lubitz, Steven A., Ellinor, Patrick T., Tai, E. Shyong, Kooner, Jaspal S., Kato, Norihiro, He, Jiang, van der Harst, Pim, Elliott, Paul, Chambers, John C., Takeuchi, Fumihiko, Johnson, Andrew D., BioBank Japan Cooperative Hospital Group, COMPASS Consortium, EPIC-CVD Consortium, EPIC-InterAct Consortium, International Stroke Genetics Consortium (ISGC), METASTROKE Consortium, Neurology Working Group of the CHARGE Consortium, NINDS Stroke Genetics Network (SiGN), UK Young Lacunar DNA Study, MEGASTROKE Consortium, Sanghera, Dharambir K., Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Longstreth, Jr, W. T., Rolfs, Arndt, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C., Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B., Kittner, Steven J., Seshadri, Sudha, Fornage, Myriam, Markus, Hugh S., Howson, Joanna M. M., Kamatani, Yoichiro, Debette, Stephanie, and Dichgans, Martin

Published
2019
Full Text
View/download PDF

21. Identification of 371 genetic variants for age at first sex and birth linked to externalising behaviour

Author

Mills, Melinda C, Tropf, Felix C, Brazel, David M, van Zuydam, Natalie, Vaez, Ahmad, eQTLGen Consortium, BIOS Consortium, Human Reproductive Behaviour Consortium, Pers, Tune H, Snieder, Harold, Perry, John RB, Ong, Ken K, den Hoed, Marcel, Barban, Nicola, Day, Felix R, Mills, Melinda C [0000-0003-1704-0001], Tropf, Felix C [0000-0003-2445-515X], Brazel, David M [0000-0001-5361-2498], Vaez, Ahmad [0000-0001-9048-3795], Pers, Tune H [0000-0003-0207-4831], Snieder, Harold [0000-0003-1949-2298], Perry, John RB [0000-0001-6483-3771], Ong, Ken K [0000-0003-4689-7530], den Hoed, Marcel [0000-0001-8081-428X], Barban, Nicola [0000-0002-4362-4652], Day, Felix R [0000-0003-3789-7651], and Apollo - University of Cambridge Repository

Subjects
Male, Adolescent, Reproduction, Age Factors, Coitus, Parturition, Humans, Female, Polymorphism, Single Nucleotide, Genetic Association Studies
Abstract

Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5-6% polygenic score prediction. Heritability of age at first birth shifted from 9% [CI = 4-14%] for women born in 1940 to 22% [CI = 19-25%] for those born in 1965. Signals are driven by the genetics of reproductive biology and externalising behaviour, with key genes related to follicle stimulating hormone (FSHB), implantation (ESR1), infertility and spermatid differentiation. Our findings suggest that polycystic ovarian syndrome may lead to later age at first birth, linking with infertility. Late age at first birth is associated with parental longevity and reduced incidence of type 2 diabetes and cardiovascular disease. Higher childhood socioeconomic circumstances and those in the highest polygenic score decile (90%+) experience markedly later reproductive onset. Results are relevant for improving teenage and late-life health, understanding longevity and guiding experimentation into mechanisms of infertility.

Published
2021

23. Erratum: Genetic loci associated with heart rate variability and their effects on cardiac disease risk

Author

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

Published
2017
Full Text
View/download PDF

24. Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression

Author

Mattis, Katia K, primary, Krentz, Nicole A J, additional, Metzendorf, Christoph, additional, Abaitua, Fernando, additional, Spigelman, Aliya F, additional, Sun, Han, additional, Rottner, Antje K, additional, Bautista, Austin, additional, Mazzaferro, Eugenia, additional, Perez-Alcantara, Marta, additional, Manning Fox, Jocelyn E, additional, Torres, Jason M, additional, Weslowska-Andersen, Agata, additional, Yu, Grace Z, additional, Mahajan, Anubha, additional, Larsson, Anders, additional, MacDonald, Patrick E, additional, Davies, Benjamin, additional, den Hoed, Marcel, additional, and Gloyn, Anna L, additional

Published
2022
Full Text
View/download PDF

28. Contribution of common non-synonymous variants in PCSK1 to body mass index variation and risk of obesity: a systematic review and meta-analysis with evidence from up to 331 175 individuals

Author

Nead, Kevin T., Li, Aihua, Wehner, Mackenzie R., Neupane, Binod, Gustafsson, Stefan, Butterworth, Adam, Engert, James C., Davis, A. Darlene, Hegele, Robert A., Miller, Ruby, den Hoed, Marcel, Khaw, Kay-Tee, Kilpeläinen, Tuomas O., Wareham, Nick, Edwards, Todd L., Hallmans, Göran, Varga, Tibor V., Kardia, Sharon L. R., Smith, Jennifer A., Zhao, Wei, Faul, Jessica D., Weir, David, Mi, Jie, Xi, Bo, Quinteros, Samuel Canizales, Cooper, Cyrus, Sayer, Avan Aihie, Jameson, Karen, Grøntved, Anders, Fornage, Myriam, Sidney, Stephen, Hanis, Craig L., Highland, Heather M., Häring, Hans-Ulrich, Heni, Martin, Lasky-Su, Jessica, Weiss, Scott T., Gerhard, Glenn S., Still, Christopher, Melka, Melkaey M., Pausova, Zdenka, Paus, Tomáš, Grant, Struan F. A., Hakonarson, Hakon, Price, R. Arlen, Wang, Kai, Scherag, Andre, Hebebrand, Johannes, Hinney, Anke, Franks, Paul W., Frayling, Timothy M., McCarthy, Mark I., Hirschhorn, Joel N., Loos, Ruth J., Ingelsson, Erik, Gerstein, Hertzel C., Yusuf, Salim, Beyene, Joseph, Anand, Sonia S., and Meyre, David

Published
2015
Full Text
View/download PDF

32. Publisher Correction: Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes (Nature Genetics, (2018), 50, 4, (524-537), 10.1038/s41588-018-0058-3)

Author

Malik, Rainer, Chauhan, Ganesh, Traylor, Matthew, Sargurupremraj, Muralidharan, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W., Gretarsdottir, Solveig, Anderson, Christopher D., Chong, Michael, Adams, Hieab H. H., Ago, Tetsuro, Almgren, Peter, Amouyel, Philippe, Ay, Hakan, Bartz, Traci M., Benavente, Oscar R., Bevan, Steve, Boncoraglio, Giorgio B., Brown, Robert D., Butterworth, Adam S., Carrera, Caty, Carty, Cara L., Chasman, Daniel I., Chen, Wei-Min, Cole, John W., Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I. W., DeStefano, Anita L., den Hoed, Marcel, Duan, Qing, Engelter, Stefan T., Falcone, Guido J., Gottesman, Rebecca F., Grewal, Raji P., Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B., Hassan, Ahamad, Havulinna, Aki S., and van der Lee, Sven J.

Abstract

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

Published
2019

34. Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Author

Strawbridge, Rona J., Silveira, Angela, den Hoed, Marcel, Gustafsson, Stefan, Luan, Jian’an, Rybin, Denis, Dupuis, Josée, Li-Gao, Ruifang, Kavousi, Maryam, Dehghan, Abbas, Haljas, Kadri, Lahti, Jari, Gådin, Jesper R., Bäcklund, Alexandra, de Faire, Ulf, Gertow, Karl, Giral, Phillipe, Goel, Anuj, Humphries, Steve E., Kurl, Sudhir, Langenberg, Claudia, Lannfelt, Lars L., Lind, Lars, Lindgren, Cecilia C.M., Mannarino, Elmo, Mook-Kanamori, Dennis O., Morris, Andrew P., de Mutsert, Renée, Rauramaa, Rainer, Saliba-Gustafsson, Peter, Sennblad, Bengt, Smit, Andries J., Syvänen, Ann-Christine, Tremoli, Elena, Veglia, Fabrizio, Zethelius, Björn, Björck, Hanna M., Eriksson, Johan G., Hofman, Albert, Franco, Oscar H., Watkins, Hugh, Jukema, J. Wouter, Florez, Jose C., Wareham, Nicholas J., Meigs, James B., Ingelsson, Erik, Baldassarre, Damiano, Hamsten, Anders, Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Epidemiology, and Erasmus MC other

Subjects
Carotid Artery Diseases, Male, EXPRESSION, endocrine system, Genetic variants, endocrine system diseases, Quantitative Trait Loci, PATHOPHYSIOLOGY, DEPENDENT DIABETES-MELLITUS, Vascular Remodeling, Carotid Intima-Media Thickness, Polymorphism, Single Nucleotide, INTIMA-MEDIA THICKNESS, Article, Gene Frequency, Risk Factors, Intima-media-thickness, Humans, Genetic Predisposition to Disease, Cardiac and Cardiovascular Systems, CORONARY-HEART-DISEASE, COHORT, cardiovascular diseases, Mendelian randomisation, EUROPEAN POPULATION, COMMON, Genetic Association Studies, Chromosomes, Human, Pair 15, Kardiologi, MEN, Single nucleotide polymorphisms, Mendelian Randomization Analysis, Atherosclerosis, INSULIN, Europe, Phenotype, Asymptomatic Diseases, Linear Models, cardiovascular system, Female, hormones, hormone substitutes, and hormone antagonists, Proinsulin
Abstract

Background and aims Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling. Methods We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants. Results We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures. Conclusions We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT., Highlights • Identification of a novel proinsulin-associated locus on chromosome 15. • Lead chromosome 15 SNP rs8029765 influences expression of UNC45A in liver. • Proinsulin effects on carotid intima-media thickness are segment-specific. • Proinsulin-increasing SNP scores had limited effects on carotid intima-media thickness. • Proinsulin is unlikely to have causal effects on intima-media thickness.

Published
2017

36. Assessing causality in the association between child adiposity and physical activity levels: a mendelian randomization analysis

Author

Richmond, Rebecca C., Smith, George Davey, Ness, Andy R., den Hoed, Marcel, McMahon, George, and Timpson, Nicholas J.

Subjects
Exercise -- Health aspects, Medical research, Medicine, Experimental, Children -- Health aspects, Causation -- Research, Biological sciences
Abstract

Background: Cross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity, and a strong inverse dose-response association with body mass index (BMI) has been found. However, few studies have explored the extent to which this association reflects reverse causation. We aimed to determine whether childhood adiposity causally influences levels of physical activity using genetic variants reliably associated with adiposity to estimate causal effects. Methods and Findings: The Avon Longitudinal Study of Parents and Children collected data on objectively assessed activity levels of 4,296 children at age 11 y with recorded BMI and genotypic data. We used 32 established genetic correlates of BMI combined in a weighted allelic score as an instrumental variable for adiposity to estimate the causal effect of adiposity on activity. In observational analysis, a 3.3 kg/[m.sup.2] (one standard deviation) higher BMI was associated with 22.3 (95% CI, 17.0, 27.6) movement counts/min less total physical activity (p = 1.6 x [10.sup.-16]), 2.6 (2.1, 3.1) min/d less moderate-to-vigorous-intensity activity (p = 3.7 x [10.sup.-29]), and 3.5 (1.5, 5.5) min/d more sedentary time (p = 5.0 x [10.sup.-4]). In Mendelian randomization analyses, the same difference in BMI was associated with 32.4 (0.9, 63.9) movement counts/min less total physical activity (p = 0.04) (~5.3% of the mean counts/minute), 2.8 (0.1, 5.5) min/d less moderate-to-vigorous-intensity activity (p = 0.04), and 13.2 (1.3, 25.2) min/d more sedentary time (p = 0.03). There was no strong evidence for a difference between variable estimates from observational estimates. Similar results were obtained using fat mass index. Low power and poor instrumentation of activity limited causal analysis of the influence of physical activity on BMI. Conclusions: Our results suggest that increased adiposity causes a reduction in physical activity in children and support research into the targeting of BMI in efforts to increase childhood activity levels. Importantly, this does not exclude lower physical activity also leading to increased adiposity, i.e., bidirectional causation. Please see later in the article for the Editors' Summary., Introduction Cross-sectional studies have shown that objectively measured physical activity is associated with childhood adiposity [1-6], and a strong inverse dose-response association with body mass index (BMI) has been found [...]

Published
2014
Full Text
View/download PDF

37. Genetic loci associated with heart rate variability and their effects on cardiac disease risk (vol 8, pg 15805, 2017)

Author

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

Subjects
Netherlands Twin Register (NTR), Cardiovascular genetics Genome-wide association studies Risk factors
Abstract

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

Published
2017
Full Text
View/download PDF

38. Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/Cas9-based approach

Author

von der Heyde, Benedikt, primary, Emmanouilidou, Anastasia, additional, Mazzaferro, Eugenia, additional, Vicenzi, Silvia, additional, Höijer, Ida, additional, Klingström, Tiffany, additional, Jumaa, Sitaf, additional, Dethlefsen, Olga, additional, Snieder, Harold, additional, de Geus, Eco, additional, Ameur, Adam, additional, Ingelsson, Erik, additional, Allalou, Amin, additional, Brooke, Hannah L., additional, and den Hoed, Marcel, additional

Published
2018
Full Text
View/download PDF

42. Genome-wide association meta-analysis of PR interval identifies 47 novel loci associated with atrial and atrioventricular electrical activity

Author

van Setten, Jessica, primary, Brody, Jennifer A., additional, Jamshidi, Yalda, additional, Swenson, Brenton R., additional, Butler, Anne M., additional, Campbell, Harry, additional, Fabiola Del Greco, M., additional, Evans, Daniel S., additional, Gibson, Quince, additional, Gudbjartsson, Daniel F., additional, Kerr, Kathleen F., additional, Krijthe, Bouwe P., additional, Lyytikäinen, Leo-Pekka, additional, Müller, Christian, additional, Müller-Nurasyid, Martina, additional, Nolte, Ilja M., additional, Padmanabhan, Sandosh, additional, Ritchie, Marylyn D., additional, Robino, Antonietta, additional, Smith, Albert V., additional, Steri, Maristella, additional, Tanaka, Toshiko, additional, Teumer, Alexander, additional, Trompet, Stella, additional, Ulivi, Sheila, additional, Verweij, Niek, additional, Yin, Xiaoyan, additional, Arnar, David O., additional, Asselbergs, Folkert W., additional, Bader, Joel S., additional, Barnard, John, additional, Bis, Josh, additional, Blankenberg, Stefan, additional, Boerwinkle, Eric, additional, Bradford, Yuki, additional, Buckley, Brendan M., additional, Chung, Mina K., additional, Crawford, Dana, additional, den Hoed, Marcel, additional, Denny, Josh, additional, Dominiczak, Anna F., additional, Ehret, Georg B., additional, Eijgelsheim, Mark, additional, Ellinor, Patrick T., additional, Felix, Stephan B., additional, Franco, Oscar H., additional, Franke, Lude, additional, Harris, Tamara B., additional, Holm, Hilma, additional, Ilaria, Gandin, additional, Iorio, Annamaria, additional, Kähönen, Mika, additional, Kolcic, Ivana, additional, Kors, Jan A., additional, Lakatta, Edward G., additional, Launer, Lenore J., additional, Lin, Honghuang, additional, Lin, Henry J., additional, Loos, Ruth J.F., additional, Lubitz, Steven A., additional, Macfarlane, Peter W., additional, Magnani, Jared W., additional, Mateo Leach, Irene, additional, Meitinger, Thomas, additional, Mitchell, Braxton D., additional, Munzel, Thomas, additional, Papanicolaou, George J., additional, Peters, Annette, additional, Pfeufer, Arne, additional, Pramstaller, Peter P., additional, Raitakari, Olli T., additional, Rotter, Jerome I., additional, Rudan, Igor, additional, Samani, Nilesh J., additional, Schlessinger, David, additional, Silva Aldana, Claudia T., additional, Sinner, Moritz F., additional, Smith, Jonathan D., additional, Snieder, Harold, additional, Soliman, Elsayed Z., additional, Spector, Timothy D., additional, Stott, David J., additional, Strauch, Konstantin, additional, Tarasov, Kirill V., additional, Uitterlinden, Andre G., additional, van Wagoner, David R., additional, Völker, Uwe, additional, Völzke, Henry, additional, Waldenberger, Melanie, additional, Westra, Harm Jan, additional, Wild, Philipp S., additional, Zeller, Tanja, additional, Alonso, Alvaro, additional, Avery, Christy L., additional, Bandinelli, Stefania, additional, Benjamin, Emelia J., additional, Cucca, Francesco, additional, Dörr, Marcus, additional, Ferrucci, Luigi, additional, Gasparini, Paolo, additional, Gudnason, Vilmundur, additional, Hayward, Caroline, additional, Heckbert, Susan R., additional, Hicks, Andrew A., additional, Jukema, J. Wouter, additional, Kääb, Stefan, additional, Lehtimäki, Terho, additional, Liu, Yongmei, additional, Munroe, Patricia B., additional, Parsa, Afshin, additional, Polasek, Ozren, additional, Psaty, Bruce M., additional, Roden, Dan M., additional, Schnabel, Renate B., additional, Sinagra, Gianfranco, additional, Stefansson, Kari, additional, Stricker, Bruno H., additional, van der Harst, Pim, additional, van Duijn, Cornelia M., additional, Wilson, James F., additional, Gharib, Sina, additional, de Bakker, Paul I.W., additional, Isaacs, Aaron, additional, Arking, Dan E., additional, and Sotoodehnia, Nona, additional

Published
2018
Full Text
View/download PDF

44. Heritability of objectively assessed daily physical activity and sedentary behavior1234

Author

den Hoed, Marcel, Brage, Søren, Zhao, Jing Hua, Westgate, Kate, Nessa, Ayrun, Ekelund, Ulf, Spector, Tim D, Wareham, Nicholas J, and Loos, Ruth JF

Subjects
Adult, Aged, 80 and over, Male, Adolescent, Twins, Monozygotic, Environment, Middle Aged, Motor Activity, Body Mass Index, Young Adult, Phenotype, Nutritional Epidemiology and Public Health, Twins, Dizygotic, Humans, Female, Gene-Environment Interaction, Sedentary Behavior, Energy Metabolism, Aged
Abstract

Background: Twin and family studies that estimated the heritability of daily physical activity have been limited by poor measurement quality and a small sample size. Objective: We examined the heritability of daily physical activity and sedentary behavior assessed objectively by using combined heart rate and movement sensing in a large twin study. Design: Physical activity traits were assessed in daily life for a mean (±SD) 6.7 ± 1.1 d in 1654 twins from 420 monozygotic and 352 dizygotic same-sex twin pairs aged 56.3 ± 10.4 y with body mass index (in kg/m2) of 26.1 ± 4.8. We estimated the average daily movement, physical activity energy expenditure, and time spent in moderate-to-vigorous intensity physical activity and sedentary behavior from heart rate and acceleration data. We used structural equation modeling to examine the contribution of additive genetic, shared environmental, and unique environmental factors to between-individual variation in traits. Results: Additive genetic factors (ie, heritability) explained 47% of the variance in physical activity energy expenditure (95% CI: 23%, 53%) and time spent in moderate-to-vigorous intensity physical activity (95% CI: 29%, 54%), 35% of the variance in acceleration of the trunk (95% CI: 0%, 44%), and 31% of the variance in the time spent in sedentary behavior (95% CI: 9%, 51%). The remaining variance was predominantly explained by unique environmental factors and random error, whereas shared environmental factors played only a marginal role for all traits with a range of 0–15%. Conclusions: The between-individual variation in daily physical activity and sedentary behavior is mainly a result of environmental influences. Nevertheless, genetic factors explain up to one-half of the variance, suggesting that innate biological processes may be driving some of our daily physical activity.

Published
2013

45. Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies

Author

Chauhan, Ganesh, primary, Arnold, Corey R, additional, Chu, Audrey Y, additional, Fornage, Myriam, additional, Reyahi, Azadeh, additional, Bis, Joshua C, additional, Havulinna, Aki S, additional, Sargurupremraj, Muralidharan, additional, Smith, Albert Vernon, additional, Adams, Hieab H H, additional, Choi, Seung Hoan, additional, Pulit, Sara L, additional, Trompet, Stella, additional, Garcia, Melissa E, additional, Manichaikul, Ani, additional, Teumer, Alexander, additional, Gustafsson, Stefan, additional, Bartz, Traci M, additional, Bellenguez, Céline, additional, Vidal, Jean Sebastien, additional, Jian, Xueqiu, additional, Kjartansson, Olafur, additional, Wiggins, Kerri L, additional, Satizabal, Claudia L, additional, Xue, Flora, additional, Ripatti, Samuli, additional, Liu, Yongmei, additional, Deelen, Joris, additional, den Hoed, Marcel, additional, Bevan, Steve, additional, Hopewell, Jemma C, additional, Malik, Rainer, additional, Heckbert, Susan R, additional, Rice, Kenneth, additional, Smith, Nicholas L, additional, Levi, Christopher, additional, Sharma, Pankaj, additional, Sudlow, Cathie LM, additional, Nik, Ali Moussavi, additional, Cole, John W, additional, Schmidt, Reinhold, additional, Meschia, James, additional, Thijs, Vincent, additional, Lindgren, Arne, additional, Melander, Olle, additional, Grewal, Raji P, additional, Sacco, Ralph L, additional, Rundek, Tatjana, additional, Rothwell, Peter M, additional, Arnett, Donna K, additional, Jern, Christina, additional, Johnson, Julie A, additional, Benavente, Oscar R, additional, Wassertheil-Smoller, Sylvia, additional, Lee, Jin-Moo, additional, Wong, Quenna, additional, Aparicio, Hugo J, additional, Engelter, Stefan T, additional, Kloss, Manja, additional, Leys, Didier, additional, Pezzini, Alessandro, additional, Buring, Julie E, additional, Ridker, Paul M, additional, Berr, Claudine, additional, Dartigues, Jean-François, additional, Hamsten, Anders, additional, Magnusson, Patrik K, additional, Traylor, Matthew, additional, Pedersen, Nancy L, additional, Lannfelt, Lars, additional, Lindgren, Lars, additional, Lindgren, Cecilia M, additional, Morris, Andrew P, additional, Jimenez-Conde, Jordi, additional, Montaner, Joan, additional, Radmanesh, Farid, additional, Slowik, Agnieszka, additional, Woo, Daniel, additional, Hofman, Albert, additional, Koudstaal, Peter J, additional, Portegies, Marileen L P, additional, Uitterlinden, André G, additional, de Craen, Anton J M, additional, Ford, Ian, additional, Jukema, J Wouter, additional, Stott, David J, additional, Allen, Norrina B, additional, Sale, Michele M, additional, Johnson, Andrew D, additional, Bennett, David A, additional, De Jager, Philip L, additional, White, Charles C, additional, Grabe, Hans Jörgen, additional, Markus, Marcello Ricardo Paulista, additional, Schminke, Ulf, additional, Boncoraglio, Giorgio B, additional, Clarke, Robert, additional, Kamatani, Yoichiro, additional, Dallongeville, Jean, additional, Lopez, Oscar L, additional, Rotter, Jerome I, additional, Nalls, Michael A, additional, Gottesman, Rebecca F, additional, Griswold, Michael E, additional, Knopman, David S, additional, Windham, B Gwen, additional, Beiser, Alexa, additional, Markus, Hugh S, additional, Vartiainen, Erkki, additional, French, Curtis R, additional, Dichgans, Martin, additional, Pastinen, Tomi, additional, Lathrop, Mark, additional, Gudnason, Vilmundur, additional, Kurth, Tobias, additional, Psaty, Bruce M, additional, Harris, Tamara B, additional, Rich, Stephen S, additional, deStefano, Anita L, additional, Schmidt, Carsten Oliver, additional, Worrall, Bradford B, additional, Rosand, Jonathan, additional, Salomaa, Veikko, additional, Mosley, Thomas H, additional, Ingelsson, Erik, additional, van Duijn, Cornelia M, additional, Tzourio, Christophe, additional, Rexrode, Kathryn M, additional, Lehmann, Ordan J, additional, Launer, Lenore J, additional, Ikram, M Arfan, additional, Carlsson, Peter, additional, Chasman, Daniel I, additional, Childs, Sarah J, additional, Longstreth, William T, additional, Seshadri, Sudha, additional, and Debette, Stéphanie, additional

Published
2016
Full Text
View/download PDF

48. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Author

Horikoshi, Momoko Yaghootkar, Hanieh Mook-Kanamori, Dennis O. and Sovio, Ulla Taal, H. Rob Hennig, Branwen J. Bradfield, Jonathan P. St Pourcain, Beate Evans, David M. Charoen, Pimphen Kaakinen, Marika Cousminer, Diana L. Lehtimaki, Terho Kreiner-Moller, Eskil Warrington, Nicole M. and Bustamante, Mariona Feenstra, Bjarke Berry, Diane J. and Thiering, Elisabeth Pfab, Thiemo Barton, Sheila J. Shields, Beverley M. Kerkhof, Marjan van Leeuwen, Elisabeth M. and Fulford, Anthony J. Kutalik, Zoltan Zhao, Jing Hua den Hoed, Marcel Mahajan, Anubha Lindi, Virpi Goh, Liang-Kee and Hottenga, Jouke-Jan Wu, Ying Raitakari, Olli T. Harder, Marie N. Meirhaeghe, Aline Ntalla, Ioanna Salem, Rany M. and Jameson, Karen A. Zhou, Kaixin Monies, Dorota M. Lagou, Vasiliki Kirin, Mirna Heikkinen, Jani Adair, Linda S. and Alkuraya, Fowzan S. Al-Odaib, Ali Amouyel, Philippe and Andersson, Ehm Astrid Bennett, Amanda J. Blakemore, Alexandra I. F. Buxton, Jessica L. Dallongeville, Jean Das, Shikta de Geus, Eco J. C. Estivill, Xavier Flexeder, Claudia Froguel, Philippe Geller, Frank Godfrey, Keith M. Gottrand, Frederic and Groves, Christopher J. Hansen, Torben Hirschhorn, Joel N. and Hofman, Albert Hollegaard, Mads V. Hougaard, David M. and Hyppoenen, Elina Inskip, Hazel M. Isaacs, Aaron Jorgensen, Torben Kanaka-Gantenbein, Christina Kemp, John P. Kiess, Wieland Kilpelainen, Tuomas O. Klopp, Norman Knight, Bridget A. Kuzawa, Christopher W. McMahon, George Newnham, John P. and Niinikoski, Harri Oostra, Ben A. Pedersen, Louise and Postma, Dirkje S. Ring, Susan M. Rivadeneira, Fernando and Robertson, Neil R. Sebert, Sylvain Simell, Olli Slowinski, Torsten Tiesler, Carla M. T. Toenjes, Anke Vaag, Allan and Viikari, Jorma S. Vink, Jacqueline M. Vissing, Nadja Hawwa and Wareham, Nicholas J. Willemsen, Gonneke Witte, Daniel R. and Zhang, Haitao Zhao, Jianhua Wilson, James F. Stumvoll, Michael Prentice, Andrew M. Meyer, Brian F. Pearson, Ewan R. and Boreham, Colin A. G. Cooper, Cyrus Gillman, Matthew W. and Dedoussis, George V. Moreno, Luis A. Pedersen, Oluf and Saarinen, Maiju Mohlke, Karen L. Boomsma, Dorret I. Saw, Seang-Mei Lakka, Timo A. Koerner, Antje Loos, Ruth J. F. and Ong, Ken K. Vollenweider, Peter van Duijn, Cornelia M. and Koppelman, Gerard H. Hattersley, Andrew T. Holloway, John W. and Hocher, Berthold Heinrich, Joachim Power, Chris Melbye, Mads and Guxens, Monica Pennell, Craig E. Bonnelykke, Klaus and Bisgaard, Hans Eriksson, Johan G. Widen, Elisabeth and Hakonarson, Hakon Uitterlinden, Andre G. Pouta, Anneli and Lawlor, Debbie A. Smith, George Davey Frayling, Timothy M. and McCarthy, Mark I. Grant, Struan F. A. Jaddoe, Vincent W. V. and Jarvelin, Marjo-Riitta Timpson, Nicholas J. Prokopenko, Inga and Freathy, Rachel M. MAGIC Early Growth Genetics EGG

Abstract

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood(1). Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits(2). In an expanded genome-wide association metaanalysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

Published
2013

49. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Author

Evans, David M, Goh, Liang-Kee, Mahajan, Anubha, Kutalik, Zoltán, Feenstra, Bjarke, Thiering, Elisabeth, Zhao, Jing Hua, Charoen, Pimphen, Kerkhof, Marjan, Hottenga, Jouke-Jan, Yaghootkar, Hanieh, Lehtimäki, Terho, Horikoshi, Momoko, Berry, Diane J, Kreiner-Møller, Eskil, Bustamante, Mariona, St Pourcain, Beate, Mook-Kanamori, Dennis O, Shields, Beverley M, Kaakinen, Marika, Bradfield, Jonathan P, Cousminer, Diana L, Lindi, Virpi, Sovio, Ulla, Fulford, Anthony J, Warrington, Nicole M, den Hoed, Marcel, Barton, Sheila J, Taal, H Rob, Pfab, Thiemo, van Leeuwen, Elisabeth M, and Hennig, Branwen J

Abstract

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood1. Previous genome-wide association studies identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes, and a second variant, near CCNL1, with no obvious link to adult traits2. In an expanded genome-wide association meta-analysis and follow-up study (up to 69,308 individuals of European descent from 43 studies), we have now extended the number of genome-wide significant loci to seven, accounting for a similar proportion of variance to maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes; ADRB1 with adult blood pressure; and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

Published
2013
Full Text
View/download PDF

50. Maternal diabetes and incidence of childhood cancer - a nationwide cohort study and exploratory genetic analysis.

Author

Deleskog, Anna, den Hoed, Marcel, Tettamanti, Giorgio, Carlsson, Sofia, Ljung, Rickard, Feychting, Maria, and Brooke, Hannah L.

Subjects
GESTATIONAL diabetes, DISEASE incidence, CHILDHOOD cancer, ETIOLOGY of cancer, BRAIN tumors
Abstract

Background: The etiology of childhood cancer is not well understood, but may be linked to prenatal and perinatal factors, such as maternal diabetes. However, this association has not been examined in depth. We aimed to determine if maternal diabetes is associated with risk of childhood brain tumor (CBT), leukemia (all types combined and acute lymphoblastic leukemia [ALL] separately), and lymphoma. Methods: All children born in Sweden between 1973 and 2014 (n=4,239,965) were followed from birth until first cancer diagnosis, age 15 years, or December 31, 2015. Data on maternal diabetes, childhood cancer, and covariates were obtained from nationwide health registers. Incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using Cox regression adjusted for potential confounders/mediators. Additionally, we performed an exploratory analysis using results from published genome-wide association studies and functional annotation. Results: Maternal diabetes was associated with lower risk of CBT (adjusted IRR [95% CI]: 0.56 [0.35-0.91]) and higher risk of leukemia (adjusted IRR: 1.47 [1.13-1.92] for all leukemia combined and 1.64 [1.23-2.18] for ALL). These associations were similar for both maternal type 1 diabetes and gestational diabetes. Associations of five previously identified genetic loci were compatible with a causal effect of diabetes traits on neuroblastoma and common Hodgkin's lymphoma. Conclusion: Children whose mother had diabetes had lower risk of CBT and higher risk of leukemia, compared with children whose mother did not have diabetes. Our results are compatible with a role of prenatal and perinatal glycemic environment in childhood cancer etiology. [ABSTRACT FROM AUTHOR]

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results