347 results on '"‘t Hart, Leen M."'
Search Results
2. Trajectories of clinical characteristics, complications and treatment choices in data-driven subgroups of type 2 diabetes
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Li, Xinyu, Donnelly, Louise A., Slieker, Roderick C., Beulens, Joline W. J., ‘t Hart, Leen M., Elders, Petra J. M., Pearson, Ewan R., van Giessen, Anoukh, Leal, Jose, and Feenstra, Talitha
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- 2024
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3. Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank
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Jin, Qiao, Lau, Eric S. H., Luk, Andrea O., Tam, Claudia H. T., Ozaki, Risa, Lim, Cadmon K. P., Wu, Hongjiang, Chow, Elaine Y. K., Kong, Alice P. S., Lee, Heung Man, Fan, Baoqi, Ng, Alex C. W., Jiang, Guozhi, Lee, Ka Fai, Siu, Shing Chung, Hui, Grace, Tsang, Chiu Chi, Lau, Kam Piu, Leung, Jenny Y., Tsang, Man-wo, Cheung, Elaine Y. N., Kam, Grace, Lau, Ip Tim, Li, June K., Yeung, Vincent T. F., Lau, Emmy, Lo, Stanley, Fung, Samuel, Cheng, Yuk Lun, Chow, Chun Chung, Yu, Weichuan, Tsui, Stephen K. W., Tomlinson, Brian, Huang, Yu, Lan, Hui-yao, Szeto, Cheuk Chun, So, Wing Yee, Jenkins, Alicia J., Fung, Erik, Muilwijk, Mirthe, Blom, Marieke T., ‘t Hart, Leen M., Chan, Juliana C. N., and Ma, Ronald C. W.
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- 2024
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4. An omics-based machine learning approach to predict diabetes progression: a RHAPSODY study
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Slieker, Roderick C., Münch, Magnus, Donnelly, Louise A., Bouland, Gerard A., Dragan, Iulian, Kuznetsov, Dmitry, Elders, Petra J. M., Rutter, Guy A., Ibberson, Mark, Pearson, Ewan R., ’t Hart, Leen M., van de Wiel, Mark A., and Beulens, Joline W. J.
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- 2024
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5. Altered blood gene expression in the obesity-related type 2 diabetes cluster may be causally involved in lipid metabolism: a Mendelian randomisation study
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de Klerk, Juliette A., Beulens, Joline W. J., Mei, Hailiang, Bijkerk, Roel, van Zonneveld, Anton Jan, Koivula, Robert W., Elders, Petra J. M., ’t Hart, Leen M., and Slieker, Roderick C.
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- 2023
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6. Identification of biomarkers for glycaemic deterioration in type 2 diabetes
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Slieker, Roderick C., Donnelly, Louise A., Akalestou, Elina, Lopez-Noriega, Livia, Melhem, Rana, Güneş, Ayşim, Abou Azar, Frederic, Efanov, Alexander, Georgiadou, Eleni, Muniangi-Muhitu, Hermine, Sheikh, Mahsa, Giordano, Giuseppe N., Åkerlund, Mikael, Ahlqvist, Emma, Ali, Ashfaq, Banasik, Karina, Brunak, Søren, Barovic, Marko, Bouland, Gerard A., Burdet, Frédéric, Canouil, Mickaël, Dragan, Iulian, Elders, Petra J. M., Fernandez, Celine, Festa, Andreas, Fitipaldi, Hugo, Froguel, Phillippe, Gudmundsdottir, Valborg, Gudnason, Vilmundur, Gerl, Mathias J., van der Heijden, Amber A., Jennings, Lori L., Hansen, Michael K., Kim, Min, Leclerc, Isabelle, Klose, Christian, Kuznetsov, Dmitry, Mansour Aly, Dina, Mehl, Florence, Marek, Diana, Melander, Olle, Niknejad, Anne, Ottosson, Filip, Pavo, Imre, Duffin, Kevin, Syed, Samreen K., Shaw, Janice L., Cabrera, Over, Pullen, Timothy J., Simons, Kai, Solimena, Michele, Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Lim, Gareth E., Estall, Jennifer, Ibberson, Mark, Beulens, Joline W. J., ’t Hart, Leen M, Pearson, Ewan R., and Rutter, Guy A.
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- 2023
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7. Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
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Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Leal Rodríguez, Cristina, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B., De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E. Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T., ‘t Hart, Leen M., Pattou, Francois, Raverdy, Violeta, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Mourby, Miranda, Kaye, Jane, Hattersley, Andrew, McDonald, Timothy, Ridderstråle, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Hansen, Torben, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, McCarthy, Mark I., Pearson, Ewan, Banasik, Karina, Rasmussen, Simon, and Brunak, Søren
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- 2023
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8. The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits
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Abecasis, Gonçalo, Akolkar, Beena, Alexander, Benjamin R., Allred, Nicholette D., Altshuler, David, Below, Jennifer E., Bergman, Richard, Beulens, Joline W.J., Blangero, John, Boehnke, Michael, Bokvist, Krister, Bottinger, Erwin, Boughton, Andrew P., Bowden, Donald, Brosnan, M. Julia, Brown, Christopher, Bruskiewicz, Kenneth, Burtt, Noël P., Carmichael, Mary, Caulkins, Lizz, Cebola, Inês, Chambers, John, Ida Chen, Yii-Der, Cherkas, Andriy, Chu, Audrey Y., Clark, Christopher, Claussnitzer, Melina, Costanzo, Maria C., Cox, Nancy J., Hoed, Marcel den, Dong, Duc, Duby, Marc, Duggirala, Ravindranath, Dupuis, Josée, Elders, Petra J.M., Engreitz, Jesse M., Fauman, Eric, Ferrer, Jorge, Flannick, Jason, Flicek, Paul, Flickinger, Matthew, Florez, Jose C., Fox, Caroline S., Frayling, Timothy M., Frazer, Kelly A., Gaulton, Kyle J., Gilbert, Clint, Gloyn, Anna L., Green, Todd, Hanis, Craig L., Hanson, Robert, Hattersley, Andrew T., Hoang, Quy, Im, Hae Kyung, Iqbal, Sidra, Jacobs, Suzanne B.R., Jang, Dong-Keun, Jordan, Tad, Kamphaus, Tania, Karpe, Fredrik, Keane, Thomas M., Kim, Seung K., Kluge, Alexandria, Koesterer, Ryan, Kudtarkar, Parul, Lage, Kasper, Lange, Leslie A., Lazar, Mitchell, Lehman, Donna, Liu, Ching-Ti, Loos, Ruth J.F., Ma, Ronald Ching-wan, MacDonald, Patrick, Massung, Jeffrey, Maurano, Matthew T., McCarthy, Mark I., McVean, Gil, Meigs, James B., Mercader, Josep M., Miller, Melissa R., Mitchell, Braxton, Mohlke, Karen L., Morabito, Samuel, Morgan, Claire, Mullican, Shannon, Narendra, Sharvari, Ng, Maggie C.Y., Nguyen, Lynette, Palmer, Colin N.A., Parker, Stephen C.J., Parrado, Antonio, Parsa, Afshin, Pawlyk, Aaron C., Pearson, Ewan R., Plump, Andrew, Province, Michael, Quertermous, Thomas, Redline, Susan, Reilly, Dermot F., Ren, Bing, Rich, Stephen S., Richards, J. Brent, Rotter, Jerome I., Ruebenacker, Oliver, Ruetten, Hartmut, Salem, Rany M., Sander, Maike, Sanders, Michael, Sanghera, Dharambir, Scott, Laura J., Sengupta, Sebanti, Siedzik, David, Sim, Xueling, Singh, Preeti, Sladek, Robert, Small, Kerrin, Smith, Philip, Stein, Peter, Spalding, Dylan, Stringham, Heather M., Sun, Ying, Susztak, Katalin, ’t Hart, Leen M., Taliun, Daniel, Taylor, Kent, Thomas, Melissa K., Todd, Jennifer A., Udler, Miriam S., Voight, Benjamin, von Grotthuss, Marcin, Wan, Andre, Welch, Ryan P., Wholley, David, Yuksel, Kaan, Zaghloul, Norann A., Jang, Dongkeun, Moriondo, Annie, Nguyen, Trang, Smadbeck, Patrick, Brandes, MacKenzie, Dornbos, Peter, Huellas-Bruskiewicz, Kenneth C., Ji, Yue, McMahon, Aoife C., Fauman, Eric B., Kamphaus, Tania Nayak, and Abecasis, Gonçalo R.
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- 2023
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9. A saturated map of common genetic variants associated with human height
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Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U., Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D., Graham, Sarah E., Mukamel, Ronen E., Spracklen, Cassandra N., Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H., Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E., Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S., Akiyama, Masato, Allison, Matthew A., Alvarez, Marcus, Andersen, Mette K., Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F., Bollepalli, Sailalitha, Bonnycastle, Lori L., Bork-Jensen, Jette, Bradfield, Jonathan P., Bradford, Yuki, Braund, Peter S., Brody, Jennifer A., Burgdorf, Kristoffer S., Cade, Brian E., Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E. Warwick, Degenhard, Frauke, Delgado, Graciela E., Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B., Engmann, Jorgen E., Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D., Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E., Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P., Goel, Anuj, Gordon, Scott D., Gorski, Mathias, Grove, Jakob, Guo, Xiuqing, Gustafsson, Stefan, Haessler, Jeffrey, Hansen, Thomas F., Havulinna, Aki S., Haworth, Simon J., He, Jing, Heard-Costa, Nancy, Hebbar, Prashantha, Hindy, George, Ho, Yuk-Lam A., Hofer, Edith, Holliday, Elizabeth, Horn, Katrin, Hornsby, Whitney E., Hottenga, Jouke-Jan, Huang, Hongyan, Huang, Jie, Huerta-Chagoya, Alicia, Huffman, Jennifer E., Hung, Yi-Jen, Huo, Shaofeng, Hwang, Mi Yeong, Iha, Hiroyuki, Ikeda, Daisuke D., Isono, Masato, Jackson, Anne U., Jäger, Susanne, Jansen, Iris E., Johansson, Ingegerd, Jonas, Jost B., Jonsson, Anna, Jørgensen, Torben, Kalafati, Ioanna-Panagiota, Kanai, Masahiro, Kanoni, Stavroula, Kårhus, Line L., Kasturiratne, Anuradhani, Katsuya, Tomohiro, Kawaguchi, Takahisa, Kember, Rachel L., Kentistou, Katherine A., Kim, Han-Na, Kim, Young Jin, Kleber, Marcus E., Knol, Maria J., Kurbasic, Azra, Lauzon, Marie, Le, Phuong, Lea, Rodney, Lee, Jong-Young, Leonard, Hampton L., Li, Shengchao A., Li, Xiaohui, Li, Xiaoyin, Liang, Jingjing, Lin, Honghuang, Lin, Shih-Yi, Liu, Jun, Liu, Xueping, Lo, Ken Sin, Long, Jirong, Lores-Motta, Laura, Luan, Jian’an, Lyssenko, Valeriya, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamakou, Vasiliki, Mangino, Massimo, Manichaikul, Ani, Marten, Jonathan, Mattheisen, Manuel, Mavarani, Laven, McDaid, Aaron F., Meidtner, Karina, Melendez, Tori L., Mercader, Josep M., Milaneschi, Yuri, Miller, Jason E., Millwood, Iona Y., Mishra, Pashupati P., Mitchell, Ruth E., Møllehave, Line T., Morgan, Anna, Mucha, Soeren, Munz, Matthias, Nakatochi, Masahiro, Nelson, Christopher P., Nethander, Maria, Nho, Chu Won, Nielsen, Aneta A., Nolte, Ilja M., Nongmaithem, Suraj S., Noordam, Raymond, Ntalla, Ioanna, Nutile, Teresa, Pandit, Anita, Christofidou, Paraskevi, Pärna, Katri, Pauper, Marc, Petersen, Eva R. B., Petersen, Liselotte V., Pitkänen, Niina, Polašek, Ozren, Poveda, Alaitz, Preuss, Michael H., Pyarajan, Saiju, Raffield, Laura M., Rakugi, Hiromi, Ramirez, Julia, Rasheed, Asif, Raven, Dennis, Rayner, Nigel W., Riveros, Carlos, Rohde, Rebecca, Ruggiero, Daniela, Ruotsalainen, Sanni E., Ryan, Kathleen A., Sabater-Lleal, Maria, Saxena, Richa, Scholz, Markus, Sendamarai, Anoop, Shen, Botong, Shi, Jingchunzi, Shin, Jae Hun, Sidore, Carlo, Sitlani, Colleen M., Slieker, Roderick C., Smit, Roelof A. J., Smith, Albert V., Smith, Jennifer A., Smyth, Laura J., Southam, Lorraine, Steinthorsdottir, Valgerdur, Sun, Liang, Takeuchi, Fumihiko, Tallapragada, Divya Sri Priyanka, Taylor, Kent D., Tayo, Bamidele O., Tcheandjieu, Catherine, Terzikhan, Natalie, Tesolin, Paola, Teumer, Alexander, Theusch, Elizabeth, Thompson, Deborah J., Thorleifsson, Gudmar, Timmers, Paul R. H. J., Trompet, Stella, Turman, Constance, Vaccargiu, Simona, van der Laan, Sander W., van der Most, Peter J., van Klinken, Jan B., van Setten, Jessica, Verma, Shefali S., Verweij, Niek, Veturi, Yogasudha, Wang, Carol A., Wang, Chaolong, Wang, Lihua, Wang, Zhe, Warren, Helen R., Bin Wei, Wen, Wickremasinghe, Ananda R., Wielscher, Matthias, Wiggins, Kerri L., Winsvold, Bendik S., Wong, Andrew, Wu, Yang, Wuttke, Matthias, Xia, Rui, Xie, Tian, Yamamoto, Ken, Yang, Jingyun, Yao, Jie, Young, Hannah, Yousri, Noha A., Yu, Lei, Zeng, Lingyao, Zhang, Weihua, Zhang, Xinyuan, Zhao, Jing-Hua, Zhao, Wei, Zhou, Wei, Zimmermann, Martina E., Zoledziewska, Magdalena, Adair, Linda S., Adams, Hieab H. H., Aguilar-Salinas, Carlos A., Al-Mulla, Fahd, Arnett, Donna K., Asselbergs, Folkert W., Åsvold, Bjørn Olav, Attia, John, Banas, Bernhard, Bandinelli, Stefania, Bennett, David A., Bergler, Tobias, Bharadwaj, Dwaipayan, Biino, Ginevra, Bisgaard, Hans, Boerwinkle, Eric, Böger, Carsten A., Bønnelykke, Klaus, Boomsma, Dorret I., Børglum, Anders D., Borja, Judith B., Bouchard, Claude, Bowden, Donald W., Brandslund, Ivan, Brumpton, Ben, Buring, Julie E., Caulfield, Mark J., Chambers, John C., Chandak, Giriraj R., Chanock, Stephen J., Chaturvedi, Nish, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Ching-Yu, Christophersen, Ingrid E., Ciullo, Marina, Cole, John W., Collins, Francis S., Cooper, Richard S., Cruz, Miguel, Cucca, Francesco, Cupples, L. Adrienne, Cutler, Michael J., Damrauer, Scott M., Dantoft, Thomas M., de Borst, Gert J., de Groot, Lisette C. P. G. M., De Jager, Philip L., de Kleijn, Dominique P. V., Janaka de Silva, H., Dedoussis, George V., den Hollander, Anneke I., Du, Shufa, Easton, Douglas F., Elders, Petra J. M., Eliassen, A. Heather, Ellinor, Patrick T., Elmståhl, Sölve, Erdmann, Jeanette, Evans, Michele K., Fatkin, Diane, Feenstra, Bjarke, Feitosa, Mary F., Ferrucci, Luigi, Ford, Ian, Fornage, Myriam, Franke, Andre, Franks, Paul W., Freedman, Barry I., Gasparini, Paolo, Gieger, Christian, Girotto, Giorgia, Goddard, Michael E., Golightly, Yvonne M., Gonzalez-Villalpando, Clicerio, Gordon-Larsen, Penny, Grallert, Harald, Grant, Struan F. A., Grarup, Niels, Griffiths, Lyn, Gudnason, Vilmundur, Haiman, Christopher, Hakonarson, Hakon, Hansen, Torben, Hartman, Catharina A., Hattersley, Andrew T., Hayward, Caroline, Heckbert, Susan R., Heng, Chew-Kiat, Hengstenberg, Christian, Hewitt, Alex W., Hishigaki, Haretsugu, Hoyng, Carel B., Huang, Paul L., Huang, Wei, Hunt, Steven C., Hveem, Kristian, Hyppönen, Elina, Iacono, William G., Ichihara, Sahoko, Ikram, M. Arfan, Isasi, Carmen R., Jackson, Rebecca D., Jarvelin, Marjo-Riitta, Jin, Zi-Bing, Jöckel, Karl-Heinz, Joshi, Peter K., Jousilahti, Pekka, Jukema, J. Wouter, Kähönen, Mika, Kamatani, Yoichiro, Kang, Kui Dong, Kaprio, Jaakko, Kardia, Sharon L. R., Karpe, Fredrik, Kato, Norihiro, Kee, Frank, Kessler, Thorsten, Khera, Amit V., Khor, Chiea Chuen, Kiemeney, Lambertus A. L. M., Kim, Bong-Jo, Kim, Eung Kweon, Kim, Hyung-Lae, Kirchhof, Paulus, Kivimaki, Mika, Koh, Woon-Puay, Koistinen, Heikki A., Kolovou, Genovefa D., Kooner, Jaspal S., Kooperberg, Charles, Köttgen, Anna, Kovacs, Peter, Kraaijeveld, Adriaan, Kraft, Peter, Krauss, Ronald M., Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lange, Leslie A., Langenberg, Claudia, Launer, Lenore J., Le Marchand, Loic, Lee, Hyejin, Lee, Nanette R., Lehtimäki, Terho, Li, Huaixing, Li, Liming, Lieb, Wolfgang, Lin, Xu, Lind, Lars, Linneberg, Allan, Liu, Ching-Ti, Liu, Jianjun, Loeffler, Markus, London, Barry, Lubitz, Steven A., Lye, Stephen J., Mackey, David A., Mägi, Reedik, Magnusson, Patrik K. E., Marcus, Gregory M., Vidal, Pedro Marques, Martin, Nicholas G., März, Winfried, Matsuda, Fumihiko, McGarrah, Robert W., McGue, Matt, McKnight, Amy Jayne, Medland, Sarah E., Mellström, Dan, Metspalu, Andres, Mitchell, Braxton D., Mitchell, Paul, Mook-Kanamori, Dennis O., Morris, Andrew D., Mucci, Lorelei A., Munroe, Patricia B., Nalls, Mike A., Nazarian, Saman, Nelson, Amanda E., Neville, Matt J., Newton-Cheh, Christopher, Nielsen, Christopher S., Nöthen, Markus M., Ohlsson, Claes, Oldehinkel, Albertine J., Orozco, Lorena, Pahkala, Katja, Pajukanta, Päivi, Palmer, Colin N. A., Parra, Esteban J., Pattaro, Cristian, Pedersen, Oluf, Pennell, Craig E., Penninx, Brenda W. J. H., Perusse, Louis, Peters, Annette, Peyser, Patricia A., Porteous, David J., Posthuma, Danielle, Power, Chris, Pramstaller, Peter P., Province, Michael A., Qi, Qibin, Qu, Jia, Rader, Daniel J., Raitakari, Olli T., Ralhan, Sarju, Rallidis, Loukianos S., Rao, Dabeeru C., Redline, Susan, Reilly, Dermot F., Reiner, Alexander P., Rhee, Sang Youl, Ridker, Paul M., Rienstra, Michiel, Ripatti, Samuli, Ritchie, Marylyn D., Roden, Dan M., Rosendaal, Frits R., Rotter, Jerome I., Rudan, Igor, Rutters, Femke, Sabanayagam, Charumathi, Saleheen, Danish, Salomaa, Veikko, Samani, Nilesh J., Sanghera, Dharambir K., Sattar, Naveed, Schmidt, Börge, Schmidt, Helena, Schmidt, Reinhold, Schulze, Matthias B., Schunkert, Heribert, Scott, Laura J., Scott, Rodney J., Sever, Peter, Shiroma, Eric J., Shoemaker, M. Benjamin, Shu, Xiao-Ou, Simonsick, Eleanor M., Sims, Mario, Singh, Jai Rup, Singleton, Andrew B., Sinner, Moritz F., Smith, J. Gustav, Snieder, Harold, Spector, Tim D., Stampfer, Meir J., Stark, Klaus J., Strachan, David P., ‘t Hart, Leen M., Tabara, Yasuharu, Tang, Hua, Tardif, Jean-Claude, Thanaraj, Thangavel A., Timpson, Nicholas J., Tönjes, Anke, Tremblay, Angelo, Tuomi, Tiinamaija, Tuomilehto, Jaakko, Tusié-Luna, Maria-Teresa, Uitterlinden, Andre G., van Dam, Rob M., van der Harst, Pim, Van der Velde, Nathalie, van Duijn, Cornelia M., van Schoor, Natasja M., Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Völzke, Henry, Wacher-Rodarte, Niels H., Walker, Mark, Wang, Ya Xing, Wareham, Nicholas J., Watanabe, Richard M., Watkins, Hugh, Weir, David R., Werge, Thomas M., Widen, Elisabeth, Wilkens, Lynne R., Willemsen, Gonneke, Willett, Walter C., Wilson, James F., Wong, Tien-Yin, Woo, Jeong-Taek, Wright, Alan F., Wu, Jer-Yuarn, Xu, Huichun, Yajnik, Chittaranjan S., Yokota, Mitsuhiro, Yuan, Jian-Min, Zeggini, Eleftheria, Zemel, Babette S., Zheng, Wei, Zhu, Xiaofeng, Zmuda, Joseph M., Zonderman, Alan B., Zwart, John-Anker, Chasman, Daniel I., Cho, Yoon Shin, Heid, Iris M., McCarthy, Mark I., Ng, Maggie C. Y., O’Donnell, Christopher J., Rivadeneira, Fernando, Thorsteinsdottir, Unnur, Sun, Yan V., Tai, E. Shyong, Boehnke, Michael, Deloukas, Panos, Justice, Anne E., Lindgren, Cecilia M., Loos, Ruth J. F., Mohlke, Karen L., North, Kari E., Stefansson, Kari, Walters, Robin G., Winkler, Thomas W., Young, Kristin L., Loh, Po-Ru, Yang, Jian, Esko, Tõnu, Assimes, Themistocles L., Auton, Adam, Abecasis, Goncalo R., Willer, Cristen J., Locke, Adam E., Berndt, Sonja I., Lettre, Guillaume, Frayling, Timothy M., Okada, Yukinori, Wood, Andrew R., Visscher, Peter M., and Hirschhorn, Joel N.
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- 2022
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10. Assessment of the bi-directional relationship between blood mitochondrial DNA copy number and type 2 diabetes mellitus: a multivariable-adjusted regression and Mendelian randomisation study
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Wang, Wenyi, Luo, Jiao, Willems van Dijk, Ko, Hägg, Sara, Grassmann, Felix, `t Hart, Leen M., van Heemst, Diana, and Noordam, Raymond
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- 2022
- Full Text
- View/download PDF
11. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids
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Ramdas, Shweta, Judd, Jonathan, Graham, Sarah E., Kanoni, Stavroula, Wang, Yuxuan, Surakka, Ida, Wenz, Brandon, Clarke, Shoa L., Chesi, Alessandra, Wells, Andrew, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J.M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Lee, Wen-Jane, Hsiung, Chao Agnes, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Schönherr, Sebastian, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Le, Phuong, Feitosa, Mary F., Wojczynski, Mary K., Hemerich, Daiane, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Noah, Tsao L., Verma, Anurag, Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Emmel, Carina, Schmidt, Börge, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S., Sankareswaran, Alagu, Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R.H.J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Morgan, Anna, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R.B., Nielsen, Aneta A., Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, He, Karen Y., Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H.H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W.J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Ida Chen, Yii-Der, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Zimmermann, Martina E., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D.C., Arnett, Donna K., Walker, Mark, Scott, Laura J., Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N.A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Lu, Fan, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, t Hart, Leen M., Elders, Petra J.M., Rader, Daniel J., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J.F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F.A., Kiemeney, Lambertus, de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O., Willems van Dijk, Ko, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Huey-Herng Sheu, Wayne, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K.E., Boomsma, Dorret I., de Geus, Eco J.C., Cupples, L. Adrienne, van Meurs, Joyce B.J., Ikram, Arfan, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Tuomilehto, Jaakko, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., Hazelhurst, Scott, Ramsay, Michèle, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, Y. Eugene, Ho, Yuk-Lam, Lynch, Julie A., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Struan Grant, Natarajan, Pradeep, Sun, Yan V., Morris, Andrew P., Deloukas, Panos, Peloso, Gina, Assimes, Themistocles L., Willer, Cristen J., Zhu, Xiang, and Brown, Christopher D.
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- 2022
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12. Diabetes risk loci-associated pathways are shared across metabolic tissues
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Bouland, Gerard A., Beulens, Joline W. J., Nap, Joey, van der Slik, Arno R., Zaldumbide, Arnaud, ’t Hart, Leen M., and Slieker, Roderick C.
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- 2022
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13. The power of genetic diversity in genome-wide association studies of lipids
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Graham, Sarah E., Clarke, Shoa L., Wu, Kuan-Han H., Kanoni, Stavroula, Zajac, Greg J. M., Ramdas, Shweta, Surakka, Ida, Ntalla, Ioanna, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Hwang, Mi Yeong, Han, Sohee, Narita, Akira, Choudhury, Ananyo, Bentley, Amy R., Ekoru, Kenneth, Verma, Anurag, Trivedi, Bhavi, Martin, Hilary C., Hunt, Karen A., Hui, Qin, Klarin, Derek, Zhu, Xiang, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Ruotsalainen, Sanni E., Havulinna, Aki S., Veturi, Yogasudha, Feng, QiPing, Rosenthal, Elisabeth A., Lingren, Todd, Pacheco, Jennifer Allen, Pendergrass, Sarah A., Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Hindy, George, Rasheed, Asif, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Willemsen, Gonneke, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Yao, Jie, Manichaikul, Ani, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Sidore, Carlo, Fiorillo, Edoardo, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Thuesen, Betina H., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Feitosa, Mary F., Wojczynski, Mary K., Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Kember, Rachel L., Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L., Marten, Jonathan, Schmidt, Börge, Arendt, Marina, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U., Yousri, Noha A., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Chai, Xiaoran, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Hung, Yi-Jen, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Gorski, Mathias, Brumat, Marco, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Xue, Chao, Zhang, Jifeng, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., Lee, Jiwon, van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Zimmermann, Martina E., Lee, Jong Young, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hildalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Schwander, Karen, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Highland, Heather M., Young, Kristin L., Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Nadkarni, Girish N., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, Konain Fatima, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Chen, Y. Eugene, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Jung, Bettina, Böger, Carsten A., Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D. C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Yajnik, Chittaranjan S., Mercader, Josep M., Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Lu, Fan, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Parra, Esteban J., Cruz, Miguel, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, ’t Hart, Leen M., Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Cucca, Francesco, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., de Geus, Eco J. C., Cupples, L. Adrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Justice, Anne E., Baras, Aris, Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Thorsteinsdottir, Unnur, Stefansson, Kari, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Rotimi, Charles N., Hazelhurst, Scott, Ramsay, Michèle, Trembath, Richard C., van Heel, David A., Tamiya, Gen, Yamamoto, Masayuki, Kim, Bong-Jo, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Natarajan, Pradeep, Peloso, Gina M., Brown, Christopher D., Morris, Andrew P., Assimes, Themistocles L., Deloukas, Panos, Sun, Yan V., and Willer, Cristen J.
- Published
- 2021
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14. Author Correction: Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
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Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Leal Rodríguez, Cristina, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B., De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E. Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T., ‘t Hart, Leen M., Pattou, Francois, Raverdy, Violeta, Brage, Soren, Kokkola, Tarja, Heggie, Alison, McEvoy, Donna, Mourby, Miranda, Kaye, Jane, Hattersley, Andrew, McDonald, Timothy, Ridderstråle, Martin, Walker, Mark, Forgie, Ian, Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Pedersen, Oluf, Hansen, Torben, Dermitzakis, Emmanouil, Franks, Paul W., Schwenk, Jochen M., Adamski, Jerzy, McCarthy, Mark I., Pearson, Ewan, Banasik, Karina, Rasmussen, Simon, and Brunak, Søren
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- 2023
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15. Replication and cross-validation of type 2 diabetes subtypes based on clinical variables: an IMI-RHAPSODY study
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Slieker, Roderick C., Donnelly, Louise A., Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J., Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Festa, Andreas, Hansen, Michael K., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J., Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido-Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A., Beulens, Joline W. J., ‘t Hart, Leen M., and Pearson, Ewan R.
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- 2021
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16. Circulating small non‐coding RNAs are associated with the insulin‐resistant and obesity‐related type 2 diabetes clusters.
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de Klerk, Juliette A., Beulens, Joline W. J., Bijkerk, Roel, van Zonneveld, Anton Jan, Elders, Petra J. M., 't Hart, Leen M., and Slieker, Roderick
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TYPE 2 diabetes ,GENE expression ,HDL cholesterol ,BODY mass index ,NON-coding RNA - Abstract
Aim: To uncover differences in small non‐coding RNAs (sncRNAs) in individuals with type 2 diabetes (T2D) categorized into five clusters based on individual characteristics, which may aid in the identification of those prone to rapid progression. Materials and Methods: In the Hoorn Diabetes Care System (DCS) cohort, participants were clustered by age, body mass index (BMI), and glycated haemoglobin, C‐peptide and high‐density lipoprotein (HDL) cholesterol levels, yielding severe insulin‐deficient diabetes, severe insulin‐resistant diabetes (SIRD), mild obesity‐related diabetes (MOD), mild diabetes, and mild diabetes with high HDL cholesterol clusters (n = 412). Utilizing plasma sncRNA‐sequencing, we identified distinct cluster‐specific sncRNAs. Validation was performed in a smaller DCS Hoorn dataset (n = 138). To elucidate their potential functions, we examined tissue expression, identified potential targets or (co‐)regulated proteins, conducted gene set enrichment analyses on the targets through Reactome, and examined tissue expression of the (co‐)regulated proteins. Results: The insulin‐resistant cluster exhibited aberrant expression of 10 sncRNAs, while the high BMI cluster featured eight differentially expressed sncRNAs. Multiple (co‐)regulated proteins were identified for sncRNAs associated with both clusters. Proteins associated with both clusters showed enrichment for metabolism. Proteins that specifically and only associated with the SIRD cluster showed enrichment for immune‐related signalling. Furthermore, MOD cluster‐specific associated proteins showed enrichment for the complement system. Conclusions: Our research showed differential sncRNA levels among type 2 diabetes clusters. This may reflect and could deepen our understanding of molecular mechanisms, in development, progression, and risk factors for each cluster. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Apolipoprotein-CIII O-Glycosylation Is Associated with Micro- and Macrovascular Complications of Type 2 Diabetes
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Naber, Annemieke, primary, Demus, Daniel, additional, Slieker, Roderick C., additional, Nicolardi, Simone, additional, Beulens, Joline W. J., additional, Elders, Petra J. M., additional, Lieverse, Aloysius G., additional, Sijbrands, Eric J. G., additional, ‘t Hart, Leen M., additional, Wuhrer, Manfred, additional, and van Hoek, Mandy, additional
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- 2024
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18. Genomics Research of Lifetime Depression in the Netherlands: The BIObanks Netherlands Internet Collaboration (BIONIC) Project
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Huider, Floris, primary, Milaneschi, Yuri, additional, Hottenga, Jouke-Jan, additional, Bot, Mariska, additional, Rietman, M. Liset, additional, Kok, Almar A.L., additional, Galesloot, Tessel E., additional, ‘t Hart, Leen M., additional, Rutters, Femke, additional, Blom, Marieke T., additional, Rhebergen, Didi, additional, Visser, Marjolein, additional, Brouwer, Ingeborg, additional, Feskens, Edith, additional, Hartman, Catharina A., additional, Oldehinkel, Albertine J., additional, de Geus, Eco J.C., additional, Kiemeney, Lambertus A., additional, Huisman, Martijn, additional, Picavet, H. Susan J., additional, Verschuren, W.M. Monique, additional, van Loo, Hanna M., additional, Penninx, Brenda W.J.H., additional, and Boomsma, Dorret I., additional
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- 2024
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19. An omics-based machine learning approach to predict diabetes progression: a RHAPSODY study
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Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiometabolic Health, Slieker, Roderick C., Münch, Magnus, Donnelly, Louise A., Bouland, Gerard A., Dragan, Iulian, Kuznetsov, Dmitry, Elders, Petra J.M., Rutter, Guy A., Ibberson, Mark, Pearson, Ewan R., ’t Hart, Leen M., van de Wiel, Mark A., Beulens, Joline W.J., Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiometabolic Health, Slieker, Roderick C., Münch, Magnus, Donnelly, Louise A., Bouland, Gerard A., Dragan, Iulian, Kuznetsov, Dmitry, Elders, Petra J.M., Rutter, Guy A., Ibberson, Mark, Pearson, Ewan R., ’t Hart, Leen M., van de Wiel, Mark A., and Beulens, Joline W.J.
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- 2024
20. Genomics Research of Lifetime Depression in the Netherlands: The BIObanks Netherlands Internet Collaboration (BIONIC) Project
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Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Huider, Floris, Milaneschi, Yuri, Hottenga, Jouke-Jan, Bot, Mariska, Rietman, M Liset, Kok, Almar A L, Galesloot, Tessel E, 't Hart, Leen M, Rutters, Femke, Blom, Marieke T, Rhebergen, Didi, Visser, Marjolein, Brouwer, Ingeborg, Feskens, Edith, Hartman, Catharina A, Oldehinkel, Albertine J, de Geus, Eco J C, Kiemeney, Lambertus A, Huisman, Martijn, Picavet, H Susan J, Verschuren, W M Monique, van Loo, Hanna M, Penninx, Brenda W J H, Boomsma, Dorret I, Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Huider, Floris, Milaneschi, Yuri, Hottenga, Jouke-Jan, Bot, Mariska, Rietman, M Liset, Kok, Almar A L, Galesloot, Tessel E, 't Hart, Leen M, Rutters, Femke, Blom, Marieke T, Rhebergen, Didi, Visser, Marjolein, Brouwer, Ingeborg, Feskens, Edith, Hartman, Catharina A, Oldehinkel, Albertine J, de Geus, Eco J C, Kiemeney, Lambertus A, Huisman, Martijn, Picavet, H Susan J, Verschuren, W M Monique, van Loo, Hanna M, Penninx, Brenda W J H, and Boomsma, Dorret I
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- 2024
21. Trajectories of clinical characteristics, complications and treatment choices in data-driven subgroups of type 2 diabetes
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Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiometabolic Health, Li, Xinyu, Donnelly, Louise A., Slieker, Roderick C., Beulens, Joline W.J., ‘t Hart, Leen M., Elders, Petra J.M., Pearson, Ewan R., van Giessen, Anoukh, Leal, Jose, Feenstra, Talitha, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiometabolic Health, Li, Xinyu, Donnelly, Louise A., Slieker, Roderick C., Beulens, Joline W.J., ‘t Hart, Leen M., Elders, Petra J.M., Pearson, Ewan R., van Giessen, Anoukh, Leal, Jose, and Feenstra, Talitha
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- 2024
22. Genomics Research of Lifetime Depression in the Netherlands : The BIObanks Netherlands Internet Collaboration (BIONIC) Project
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Huider, Floris, Milaneschi, Yuri, Hottenga, Jouke Jan, Bot, Mariska, Rietman, Liset, Kok, Almar A.L., Galesloot, Tessel E., T' Hart, Leen M., Rutters, Femke, Blom, Marieke T., Rhebergen, Didi, Visser, Marjolein, Brouwer, Ingeborg, Feskens, Edith, Hartman, Catharina A., Oldehinkel, Albertine J., De Geus, Eco J.C., Kiemeney, Lambertus A., Huisman, Martijn, Picavet, Susan J., Verschuren, Monique, Van Loo, Hanna M., Penninx, Brenda W.J.H., Boomsma, Dorret I., Huider, Floris, Milaneschi, Yuri, Hottenga, Jouke Jan, Bot, Mariska, Rietman, Liset, Kok, Almar A.L., Galesloot, Tessel E., T' Hart, Leen M., Rutters, Femke, Blom, Marieke T., Rhebergen, Didi, Visser, Marjolein, Brouwer, Ingeborg, Feskens, Edith, Hartman, Catharina A., Oldehinkel, Albertine J., De Geus, Eco J.C., Kiemeney, Lambertus A., Huisman, Martijn, Picavet, Susan J., Verschuren, Monique, Van Loo, Hanna M., Penninx, Brenda W.J.H., and Boomsma, Dorret I.
- Abstract
In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.
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- 2024
23. Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug–metabolite atlas
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Liu, Jun, Lahousse, Lies, Nivard, Michel G., Bot, Mariska, Chen, Lianmin, van Klinken, Jan Bert, Thesing, Carisha S., Beekman, Marian, van den Akker, Erik Ben, Slieker, Roderick C., Waterham, Eveline, van der Kallen, Carla J. H., de Boer, Irene, Li-Gao, Ruifang, Vojinovic, Dina, Amin, Najaf, Radjabzadeh, Djawad, Kraaij, Robert, Alferink, Louise J. M., Murad, Sarwa Darwish, Uitterlinden, André G., Willemsen, Gonneke, Pool, Rene, Milaneschi, Yuri, van Heemst, Diana, Suchiman, H. Eka D., Rutters, Femke, Elders, Petra J. M., Beulens, Joline W. J., van der Heijden, Amber A. W. A., van Greevenbroek, Marleen M. J., Arts, Ilja C. W., Onderwater, Gerrit L. J., van den Maagdenberg, Arn M. J. M., Mook-Kanamori, Dennis O., Hankemeier, Thomas, Terwindt, Gisela M., Stehouwer, Coen D. A., Geleijnse, Johanna M., ‘t Hart, Leen M., Slagboom, P. Eline, van Dijk, Ko Willems, Zhernakova, Alexandra, Fu, Jingyuan, Penninx, Brenda W. J. H., Boomsma, Dorret I., Demirkan, Ayşe, Stricker, Bruno H. C., and van Duijn, Cornelia M.
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- 2020
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24. Apolipoprotein-CIII O-Glycosylation, a Link between GALNT2 and Plasma Lipids
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Naber, Annemieke, primary, Demus, Daniel, additional, Slieker, Roderick, additional, Nicolardi, Simone, additional, Beulens, Joline W. J., additional, Elders, Petra J. M., additional, Lieverse, Aloysius G., additional, Sijbrands, Eric J. G., additional, ’t Hart, Leen M., additional, Wuhrer, Manfred, additional, and van Hoek, Mandy, additional
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- 2023
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25. Multi-omics subgroups associated with glycaemic deterioration in type 2 diabetes: an IMI-RHAPSODY Study.
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Shiying Li, Dragan, Iulian, Tran, Van Du T., Chun Ho Fung, Kuznetsov, Dmitry, Hansen, Michael K., Beulens, Joline W. J., t Hart, Leen M., Slieker, Roderick C., Donnelly, Louise A., Gerl, Mathias J., Klose, Christian, Mehl, Florence, Simons, Kai, Elders, Petra J. M., Pearson, Ewan R., Rutter, Guy A., and Ibberson, Mark
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TYPE 2 diabetes ,MULTIOMICS ,INTERLEUKIN receptors ,BLOOD lipids ,INSULIN ,INSULIN sensitivity ,INSULIN aspart - Abstract
Introduction: Type 2 diabetes (T2D) onset, progression and outcomes differ substantially between individuals. Multi-omics analyses may allow a deeper understanding of these differences and ultimately facilitate personalised treatments. Here, in an unsupervised "bottom-up" approach, we attempt to group T2D patients based solely on -omics data generated from plasma. Methods: Circulating plasma lipidomic and proteomic data from two independent clinical cohorts, Hoorn Diabetes Care System (DCS) and Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS), were analysed using Similarity Network Fusion. The resulting patient network was analysed with Logistic and Cox regression modelling to explore relationships between plasma -omic profiles and clinical characteristics. Results: From a total of 1,134 subjects in the two cohorts, levels of 180 circulating plasma lipids and 1195 proteins were used to separate patients into two subgroups. These differed in terms of glycaemic deterioration (Hazard Ratio=0.56;0.73), insulin sensitivity and secretion (C-peptide, p=3.7e-11;2.5e-06, DCS and GoDARTS, respectively; Homeostatic model assessment 2 (HOMA2)-B; -IR; -S, p=0.0008;4.2e-11;1.1e-09, only in DCS). The main molecular signatures separating the two groups included triacylglycerols, sphingomyelin, testican-1 and interleukin 18 receptor. Conclusions: Using an unsupervised network-based fusion method on plasma lipidomics and proteomics data from two independent cohorts, we were able to identify two subgroups of T2D patients differing in terms of disease severity. The molecular signatures identified within these subgroups provide insights into disease mechanisms and possibly new prognostic markers for T2D. [ABSTRACT FROM AUTHOR]
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- 2024
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26. IgG N‐glycans are associated with prevalent and incident complications of type 2 diabetes
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Memarian, Elham, primary, Heijmans, Ralph, additional, Slieker, Roderick C., additional, Sierra, Adriana, additional, Gornik, Olga, additional, Beulens, Joline W. J., additional, Hanic, Maja, additional, Elders, Petra, additional, Pascual, Julio, additional, Sijbrands, Eric, additional, Lauc, Gordan, additional, Dotz, Viktoria, additional, Barrios, Clara, additional, ’t Hart, Leen M., additional, Wuhrer, Manfred, additional, and van Hoek, Mandy, additional
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- 2023
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27. Visit-to-visit variability of glycemia and vascular complications: the Hoorn Diabetes Care System cohort
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Slieker, Roderick C., van der Heijden, Amber A. W. H., Nijpels, Giel, Elders, Petra J. M., ’t Hart, Leen M., and Beulens, Joline W. J.
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- 2019
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28. Apolipoprotein-CIII O-Glycosylation, a Link between GALNT2 and Plasma Lipids
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Naber, Annemieke, Demus, Daniel, Slieker, Roderick, Nicolardi, Simone, Beulens, Joline W.J., Elders, Petra J.M., Lieverse, Aloysius G., Sijbrands, Eric J.G., ’t Hart, Leen M., Wuhrer, Manfred, van Hoek, Mandy, Naber, Annemieke, Demus, Daniel, Slieker, Roderick, Nicolardi, Simone, Beulens, Joline W.J., Elders, Petra J.M., Lieverse, Aloysius G., Sijbrands, Eric J.G., ’t Hart, Leen M., Wuhrer, Manfred, and van Hoek, Mandy
- Abstract
Apolipoprotein-CIII (apo-CIII) is involved in triglyceride-rich lipoprotein metabolism and linked to beta-cell damage, insulin resistance, and cardiovascular disease. Apo-CIII exists in four main proteoforms: non-glycosylated (apo-CIII0a), and glycosylated apo-CIII with zero, one, or two sialic acids (apo-CIII0c, apo-CIII1 and apo-CIII2). Our objective is to determine how apo-CIII glycosylation affects lipid traits and type 2 diabetes prevalence, and to investigate the genetic basis of these relations with a genome-wide association study (GWAS) on apo-CIII glycosylation. We conducted GWAS on the four apo-CIII proteoforms in the DiaGene study in people with and without type 2 diabetes (n = 2318). We investigated the relations of the identified genetic loci and apo-CIII glycosylation with lipids and type 2 diabetes. The associations of the genetic variants with lipids were replicated in the Diabetes Care System (n = 5409). Rs4846913-A, in the GALNT2-gene, was associated with decreased apo-CIII0a. This variant was associated with increased high-density lipoprotein cholesterol and decreased triglycerides, while high apo-CIII0a was associated with raised high-density lipoprotein-cholesterol and triglycerides. Rs67086575-G, located in the IFT172-gene, was associated with decreased apo-CIII2 and with hypertriglyceridemia. In line, apo-CIII2 was associated with low triglycerides. On a genome-wide scale, we confirmed that the GALNT2-gene plays a major role i O-glycosylation of apolipoprotein-CIII, with subsequent associations with lipid parameters. We newly identified the IFT172/NRBP1 region, in the literature previously associated with hypertriglyceridemia, as involved in apolipoprotein-CIII sialylation and hypertriglyceridemia. These results link genomics, glycosylation, and lipid metabolism, and represent a key step towards unravelling the importance of O-glycosylation in health and
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- 2023
29. IgG N-glycans are associated with prevalent and incident complications of type 2 diabetes
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Memarian, Elham, Heijmans, Ralph, Slieker, Roderick C., Sierra, Adriana, Gornik, Olga, Beulens, Joline W.J., Hanic, Maja, Elders, Petra, Pascual, Julio, Sijbrands, Eric, Lauc, Gordan, Dotz, Viktoria, Barrios, Clara, ’t Hart, Leen M., Wuhrer, Manfred, van Hoek, Mandy, Memarian, Elham, Heijmans, Ralph, Slieker, Roderick C., Sierra, Adriana, Gornik, Olga, Beulens, Joline W.J., Hanic, Maja, Elders, Petra, Pascual, Julio, Sijbrands, Eric, Lauc, Gordan, Dotz, Viktoria, Barrios, Clara, ’t Hart, Leen M., Wuhrer, Manfred, and van Hoek, Mandy
- Abstract
Aims/Hypothesis:Inflammation is important in the development of type 2 diabetes complications. The N-glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N-glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N-glycosylation of IgG may be related to the development of complications of type 2 diabetes. Methods: In three independent type 2 diabetes cohorts, plasma IgG N-glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N-glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox- and logistic regression, followed by meta-analyses. The models were adjusted for age and sex and additionally for clinical risk factors. Results: IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex. Conclusions: We showed that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N-glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.
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- 2023
30. Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models:[with Author Correction]
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Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B, De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T, 't Hart, Leen M, Pattou, Francois, Raverdy, Violeta, Brage, Soren, Ridderstråle, Martin, Pedersen, Oluf, Hansen, Torben, Banasik, Karina, Rasmussen, Simon, Brunak, Søren, Allesøe, Rosa Lundbye, Lundgaard, Agnete Troen, Hernández Medina, Ricardo, Aguayo-Orozco, Alejandro, Johansen, Joachim, Nissen, Jakob Nybo, Brorsson, Caroline, Mazzoni, Gianluca, Niu, Lili, Biel, Jorge Hernansanz, Brasas, Valentas, Webel, Henry, Benros, Michael Eriksen, Pedersen, Anders Gorm, Chmura, Piotr Jaroslaw, Jacobsen, Ulrik Plesner, Mari, Andrea, Koivula, Robert, Mahajan, Anubha, Vinuela, Ana, Tajes, Juan Fernandez, Sharma, Sapna, Haid, Mark, Hong, Mun-Gwan, Musholt, Petra B, De Masi, Federico, Vogt, Josef, Pedersen, Helle Krogh, Gudmundsdottir, Valborg, Jones, Angus, Kennedy, Gwen, Bell, Jimmy, Thomas, E Louise, Frost, Gary, Thomsen, Henrik, Hansen, Elizaveta, Hansen, Tue Haldor, Vestergaard, Henrik, Muilwijk, Mirthe, Blom, Marieke T, 't Hart, Leen M, Pattou, Francois, Raverdy, Violeta, Brage, Soren, Ridderstråle, Martin, Pedersen, Oluf, Hansen, Torben, Banasik, Karina, Rasmussen, Simon, and Brunak, Søren
- Abstract
The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug-omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug-drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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- 2023
31. Potential Value of Identifying Type 2 Diabetes Subgroups for Guiding Intensive Treatment: A Comparison of Novel Data-Driven Clustering With Risk-Driven Subgroups
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Li, Xinyu, primary, van Giessen, Anoukh, additional, Altunkaya, James, additional, Slieker, Roderick C., additional, Beulens, Joline W.J., additional, ‘t Hart, Leen M., additional, Pearson, Ewan R., additional, Elders, Petra J.M., additional, Feenstra, Talitha L., additional, and Leal, Jose, additional
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- 2023
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32. The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits
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Costanzo, Maria C., primary, von Grotthuss, Marcin, additional, Massung, Jeffrey, additional, Jang, Dongkeun, additional, Caulkins, Lizz, additional, Koesterer, Ryan, additional, Gilbert, Clint, additional, Welch, Ryan P., additional, Kudtarkar, Parul, additional, Hoang, Quy, additional, Boughton, Andrew P., additional, Singh, Preeti, additional, Sun, Ying, additional, Duby, Marc, additional, Moriondo, Annie, additional, Nguyen, Trang, additional, Smadbeck, Patrick, additional, Alexander, Benjamin R., additional, Brandes, MacKenzie, additional, Carmichael, Mary, additional, Dornbos, Peter, additional, Green, Todd, additional, Huellas-Bruskiewicz, Kenneth C., additional, Ji, Yue, additional, Kluge, Alexandria, additional, McMahon, Aoife C., additional, Mercader, Josep M., additional, Ruebenacker, Oliver, additional, Sengupta, Sebanti, additional, Spalding, Dylan, additional, Taliun, Daniel, additional, Smith, Philip, additional, Thomas, Melissa K., additional, Akolkar, Beena, additional, Brosnan, M. Julia, additional, Cherkas, Andriy, additional, Chu, Audrey Y., additional, Fauman, Eric B., additional, Fox, Caroline S., additional, Kamphaus, Tania Nayak, additional, Miller, Melissa R., additional, Nguyen, Lynette, additional, Parsa, Afshin, additional, Reilly, Dermot F., additional, Ruetten, Hartmut, additional, Wholley, David, additional, Zaghloul, Norann A., additional, Abecasis, Gonçalo R., additional, Altshuler, David, additional, Keane, Thomas M., additional, McCarthy, Mark I., additional, Gaulton, Kyle J., additional, Florez, Jose C., additional, Boehnke, Michael, additional, Burtt, Noël P., additional, Flannick, Jason, additional, Abecasis, Gonçalo, additional, Allred, Nicholette D., additional, Below, Jennifer E., additional, Bergman, Richard, additional, Beulens, Joline W.J., additional, Blangero, John, additional, Bokvist, Krister, additional, Bottinger, Erwin, additional, Bowden, Donald, additional, Brown, Christopher, additional, Bruskiewicz, Kenneth, additional, Cebola, Inês, additional, Chambers, John, additional, Ida Chen, Yii-Der, additional, Clark, Christopher, additional, Claussnitzer, Melina, additional, Costanzo, Maria C., additional, Cox, Nancy J., additional, Hoed, Marcel den, additional, Dong, Duc, additional, Duggirala, Ravindranath, additional, Dupuis, Josée, additional, Elders, Petra J.M., additional, Engreitz, Jesse M., additional, Fauman, Eric, additional, Ferrer, Jorge, additional, Flicek, Paul, additional, Flickinger, Matthew, additional, Frayling, Timothy M., additional, Frazer, Kelly A., additional, Gloyn, Anna L., additional, Hanis, Craig L., additional, Hanson, Robert, additional, Hattersley, Andrew T., additional, Im, Hae Kyung, additional, Iqbal, Sidra, additional, Jacobs, Suzanne B.R., additional, Jang, Dong-Keun, additional, Jordan, Tad, additional, Kamphaus, Tania, additional, Karpe, Fredrik, additional, Kim, Seung K., additional, Lage, Kasper, additional, Lange, Leslie A., additional, Lazar, Mitchell, additional, Lehman, Donna, additional, Liu, Ching-Ti, additional, Loos, Ruth J.F., additional, Ma, Ronald Ching-wan, additional, MacDonald, Patrick, additional, Maurano, Matthew T., additional, McVean, Gil, additional, Meigs, James B., additional, Mitchell, Braxton, additional, Mohlke, Karen L., additional, Morabito, Samuel, additional, Morgan, Claire, additional, Mullican, Shannon, additional, Narendra, Sharvari, additional, Ng, Maggie C.Y., additional, Palmer, Colin N.A., additional, Parker, Stephen C.J., additional, Parrado, Antonio, additional, Pawlyk, Aaron C., additional, Pearson, Ewan R., additional, Plump, Andrew, additional, Province, Michael, additional, Quertermous, Thomas, additional, Redline, Susan, additional, Ren, Bing, additional, Rich, Stephen S., additional, Richards, J. Brent, additional, Rotter, Jerome I., additional, Salem, Rany M., additional, Sander, Maike, additional, Sanders, Michael, additional, Sanghera, Dharambir, additional, Scott, Laura J., additional, Siedzik, David, additional, Sim, Xueling, additional, Sladek, Robert, additional, Small, Kerrin, additional, Stein, Peter, additional, Stringham, Heather M., additional, Susztak, Katalin, additional, ’t Hart, Leen M., additional, Taylor, Kent, additional, Todd, Jennifer A., additional, Udler, Miriam S., additional, Voight, Benjamin, additional, Wan, Andre, additional, and Yuksel, Kaan, additional
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- 2023
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33. HbA1c is associated with altered expression in blood of cell cycle- and immune response-related genes
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Slieker, Roderick C., van der Heijden, Amber A. W. A., van Leeuwen, Nienke, Mei, Hailiang, Nijpels, Giel, Beulens, Joline W. J., and ’t Hart, Leen M.
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- 2017
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34. Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study
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Molnos, Sophie, Wahl, Simone, Haid, Mark, Eekhoff, E. Marelise W., Pool, René, Floegel, Anna, Deelen, Joris, Much, Daniela, Prehn, Cornelia, Breier, Michaela, Draisma, Harmen H., van Leeuwen, Nienke, Simonis-Bik, Annemarie M. C., Jonsson, Anna, Willemsen, Gonneke, Bernigau, Wolfgang, Wang-Sattler, Rui, Suhre, Karsten, Peters, Annette, Thorand, Barbara, Herder, Christian, Rathmann, Wolfgang, Roden, Michael, Gieger, Christian, Kramer, Mark H. H., van Heemst, Diana, Pedersen, Helle K., Gudmundsdottir, Valborg, Schulze, Matthias B., Pischon, Tobias, de Geus, Eco J. C., Boeing, Heiner, Boomsma, Dorret I., Ziegler, Anette G., Slagboom, P. Eline, Hummel, Sandra, Beekman, Marian, Grallert, Harald, Brunak, Søren, McCarthy, Mark I., Gupta, Ramneek, Pearson, Ewan R., Adamski, Jerzy, and ’t Hart, Leen M.
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- 2017
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35. Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts
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Atabaki-Pasdar, Naeimeh, Ohlsson, Mattias, Viñuela, Ana, Frau, Francesca, Pomares-Millan, Hugo, Haid, Mark, Jones, Angus G., Thomas, E. Louise, Koivula, Robert W., Kurbasic, Azra, Mutie, Pascal M., Fitipaldi, Hugo, Fernandez, Juan, Dawed, Adem Y., Giordano, Giuseppe N., Forgie, Ian M., McDonald, Timothy J., Rutters, Femke, Cederberg, Henna, Chabanova, Elizaveta, Dale, Matilda, Masi, Federico De, Thomas, Cecilia Engel, Allin, Kristine H., Hansen, Tue H., Heggie, Alison, Hong, Mun-Gwan, Elders, Petra J. M., Kennedy, Gwen, Kokkola, Tarja, Pedersen, Helle Krogh, Mahajan, Anubha, McEvoy, Donna, Pattou, Francois, Raverdy, Violeta, Häussler, Ragna S., Sharma, Sapna, Thomsen, Henrik S., Vangipurapu, Jagadish, Vestergaard, Henrik, 't Hart, Leen M., Adamski, Jerzy, Musholt, Petra B., Brage, Soren, Brunak, Søren, Dermitzakis, Emmanouil, Frost, Gary, Hansen, Torben, Laakso, Markku, Pedersen, Oluf, Ridderstråle, Martin, Ruetten, Hartmut, Hattersley, Andrew T., Walker, Mark, Beulens, Joline W. J., Mari, Andrea, Schwenk, Jochen M., Gupta, Ramneek, McCarthy, Mark I., Pearson, Ewan R., Bell, Jimmy D., Pavo, Imre, Franks, Paul W., Howard, Helen, and Moyer, Caitlin
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Risk factors ,Health aspects ,Diagnostic imaging -- Health aspects ,Machine learning -- Health aspects ,Type 2 diabetes -- Risk factors ,Enzymes -- Health aspects ,Fatty liver -- Risk factors - Abstract
Author(s): Naeimeh Atabaki-Pasdar 1, Mattias Ohlsson 2,3, Ana Viñuela 4,5,6, Francesca Frau 7, Hugo Pomares-Millan 1, Mark Haid 8, Angus G. Jones 9, E. Louise Thomas 10, Robert W. Koivula [...], Background Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. Methods and findings We utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n = 795) or at high risk of developing the disease (n = 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content ( Conclusions In this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see: https://www.predictliverfat.org/) and made it available to the community. Trial registration ClinicalTrials.gov NCT03814915.
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- 2020
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36. Author Correction : The power of genetic diversity in genome-wide association studies of lipids
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Graham, Sarah E., Clarke, Shoa L., Wu, Kuan-Han H., Kanoni, Stavroula, Zajac, Greg J. M., Ramdas, Shweta, Surakka, Ida, Ntalla, Ioanna, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Hwang, Mi Yeong, Han, Sohee, Narita, Akira, Choudhury, Ananyo, Bentley, Amy R., Ekoru, Kenneth, Verma, Anurag, Trivedi, Bhavi, Martin, Hilary C., Hunt, Karen A., Hui, Qin, Klarin, Derek, Zhu, Xiang, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Ruotsalainen, Sanni E., Havulinna, Aki S., Veturi, Yogasudha, Feng, QiPing, Rosenthal, Elisabeth A., Lingren, Todd, Pacheco, Jennifer Allen, Pendergrass, Sarah A., Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Hindy, George, Rasheed, Asif, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Mahajan, Anubha, Brown, Michael R., Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M., Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Willemsen, Gonneke, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Yao, Jie, Manichaikul, Ani, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Sidore, Carlo, Fiorillo, Edoardo, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Thuesen, Betina H., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Daw, E. Warwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Feitosa, Mary F., Wojczynski, Mary K., Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Kember, Rachel L., Slieker, Roderick C., Lo, Ken Sin, Zilhao, Nuno R., Le, Phuong, Kleber, Marcus E., Delgado, Graciela E., Huo, Shaofeng, Ikeda, Daisuke D., Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L., Marten, Jonathan, Schmidt, Börge, Arendt, Marina, Smyth, Laura J., Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U., Yousri, Noha A., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., Chai, Xiaoran, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N., Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C., Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Hung, Yi-Jen, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Gorski, Mathias, Brumat, Marco, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Xue, Chao, Zhang, Jifeng, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., Lee, Jiwon, van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Zimmermann, Martina E., Lee, Jong Young, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W., Wang, Carol A., Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hildalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Schwander, Karen, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Highland, Heather M., Young, Kristin L., Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., Nadkarni, Girish N., Launer, Lenore J., Li, Huaixing, Nalls, Mike A., Raitakari, Olli T., Ichihara, Sahoko, Wild, Sarah H., Nelson, Christopher P., Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S., Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, Konain Fatima, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H. H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W., Kraaijeveld, Adriaan O., Beulens, Joline W. J., Shu, Xiao-Ou, Rallidis, Loukianos S., Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W., Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E., Mori, Trevor A., Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M., Stark, Klaus J., Völzke, Henry, Homuth, Georg, Evans, Michele K., Zonderman, Alan B., Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E., Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J., Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Chen, Y. Eugene, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Jung, Bettina, Böger, Carsten A., Joshi, Peter K., Bennett, David A., De Jager, Philip L., Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J., Munroe, Patricia B., Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J., Kaprio, Jaakko, Pajukanta, Päivi, Adair, Linda S., Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R., Krauss, Ronald M., Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I., Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G., Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E., Golightly, Yvonne M., Wilson, James F., Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J., Rao, D.C., Arnett, Donna K., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Yajnik, Chittaranjan S., Mercader, Josep M., Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E. Shyong, van Dam, Rob M., Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F., McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I., Palmer, Colin N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Lu, Fan, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Parra, Esteban J., Cruz, Miguel, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, ’t Hart, Leen M., Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W., Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V., Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Cucca, Francesco, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., de Geus, Eco J. C., Cupples, L. Adrienne, van Meurs, Joyce B. J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J., Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C., Kooner, Jaspal S., de Vries, Paul S., Morrison, Alanna C., North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G., Whitfield, John B., Abbas, Shahid, Saleheen, Danish, Walters, Robin G., Holmes, Michael V., Black, Corri, Smith, Blair H., Justice, Anne E., Baras, Aris, Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Wei, Wei-Qi, Jarvik, Gail P., Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D., Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Thorsteinsdottir, Unnur, Stefansson, Kari, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter, Rotimi, Charles N., Hazelhurst, Scott, Ramsay, Michèle, Trembath, Richard C., van Heel, David A., Tamiya, Gen, Yamamoto, Masayuki, Kim, Bong-Jo, Mohlke, Karen L., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Boehnke, Michael, Natarajan, Pradeep, Peloso, Gina M., Brown, Christopher D., Morris, Andrew P., Assimes, Themistocles L., Deloukas, Panos, Sun, Yan V., and Willer, Cristen J.
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Medizin - Abstract
Correction to: Nature Published online 9 December 2021 In the version of this article initially published, Noha A. Yousri (Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar and Department of Computer and Systems Engineering, Alexandria University, Egypt) and Steven C. Hunt (Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA and Department of Genetic Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar) were not included in the author list. In addition, Hieab H. H. Adams (Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands and Department of Clinical Genetics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands) was shown with an incorrect second affiliation in the HTML and PDF versions of the article. Finally, in the HTML version, Cristen J. Willer was mistakenly listed with an extra affiliation (Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia). The authors and affiliations have been corrected in the HTML and PDF versions of the article.
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- 2023
37. Genome-Wide Meta-analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas
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Dawed, Adem Y., Yee, Sook Wah, Zhou, Kaixin, van Leeuwen, Nienke, Zhang, Yanfei, Siddiqui, Moneeza K., Etheridge, Amy, Innocenti, Federico, Xu, Fei, Li, Josephine H., Beulens, Joline W., van der Heijden, Amber A., Slieker, Roderick C., Chang, Yu-Chuan, Mercader, Josep M., Kaur, Varinderpal, Witte, John S., Lee, Ming Ta Michael, Kamatani, Yoichiro, Momozawa, Yukihide, Kubo, Michiaki, Palmer, Colin N.A., Florez, Jose C., Hedderson, Monique M., ‘t Hart, Leen M., Giacomini, Kathleen M., Pearson, Ewan R., Pearson, Ewan, Dawed, Adem, Holman, Rury, Coleman, Ruth, ‘t Hart, Leen, Slieker, Roderick, Beulens, Joline, van der Heijden, Amber, Nijpels, Giel, Elders, Petra, Rutters, Femke, Stricker, Bruno, Ahmadizar, Fariba, de Keyser, Catherine, Koov, Adriaan, Out, Mattijs, Kloviņš, Jānis, Zaharenko, Linda, Javorsky, Martin, Tkac, Ivan, Florez, Jose, Giacomini, Kathy, Wah Yee, Sook, Hedderson, Monique, Motsinger-Reif, Alison, Wagner, Michael, Semiz, Sabina, Dujic, Tanja, Christensen, Mette, Brøsen, Kim, Waterworth, Dawn, Ehm, Meg, Ma, Ronald, Psaty, Bruce, Floyd, James, Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, General practice, and APH - Methodology
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Advanced and Specialized Nursing ,business.industry ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,medicine.disease ,Bioinformatics ,Sulfonylurea ,Metformin ,Meta-analysis ,Expression quantitative trait loci ,Internal Medicine ,medicine ,Epidemiology/Health Services Research ,business ,Genetic association ,Glycemic ,medicine.drug ,Glipizide - Abstract
OBJECTIVE Sulfonylureas, the first available drugs for the management of type 2 diabetes, remain widely prescribed today. However, there exists significant variability in glycemic response to treatment. We aimed to establish heritability of sulfonylurea response and identify genetic variants and interacting treatments associated with HbA1c reduction. RESEARCH DESIGN AND METHODS As an initiative of the Metformin Genetics Plus Consortium (MetGen Plus) and the DIabetes REsearCh on patient straTification (DIRECT) consortium, 5,485 White Europeans with type 2 diabetes treated with sulfonylureas were recruited from six referral centers in Europe and North America. We first estimated heritability using the generalized restricted maximum likelihood approach and then undertook genome-wide association studies of glycemic response to sulfonylureas measured as HbA1c reduction after 12 months of therapy followed by meta-analysis. These results were supported by acute glipizide challenge in humans who were naïve to type 2 diabetes medications, cis expression quantitative trait loci (eQTL), and functional validation in cellular models. Finally, we examined for possible drug-drug-gene interactions. RESULTS After establishing that sulfonylurea response is heritable (mean ± SEM 37 ± 11%), we identified two independent loci near the GXYLT1 and SLCO1B1 genes associated with HbA1c reduction at a genome-wide scale (P < 5 × 10−8). The C allele at rs1234032, near GXYLT1, was associated with 0.14% (1.5 mmol/mol), P = 2.39 × 10−8), lower reduction in HbA1c. Similarly, the C allele was associated with higher glucose trough levels (β = 1.61, P = 0.005) in healthy volunteers in the SUGAR-MGH given glipizide (N = 857). In 3,029 human whole blood samples, the C allele is a cis eQTL for increased expression of GXYLT1 (β = 0.21, P = 2.04 × 10−58). The C allele of rs10770791, in an intronic region of SLCO1B1, was associated with 0.11% (1.2 mmol/mol) greater reduction in HbA1c (P = 4.80 × 10−8). In 1,183 human liver samples, the C allele at rs10770791 is a cis eQTL for reduced SLCO1B1 expression (P = 1.61 × 10−7), which, together with functional studies in cells expressing SLCO1B1, supports a key role for hepatic SLCO1B1 (encoding OATP1B1) in regulation of sulfonylurea transport. Further, a significant interaction between statin use and SLCO1B1 genotype was observed (P = 0.001). In statin nonusers, C allele homozygotes at rs10770791 had a large absolute reduction in HbA1c (0.48 ± 0.12% [5.2 ± 1.26 mmol/mol]), equivalent to that associated with initiation of a dipeptidyl peptidase 4 inhibitor. CONCLUSIONS We have identified clinically important genetic effects at genome-wide levels of significance, and important drug-drug-gene interactions, which include commonly prescribed statins. With increasing availability of genetic data embedded in clinical records these findings will be important in prescribing glucose-lowering drugs.
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- 2021
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38. Novel subgroups of type 2 diabetes based on multi-Omics profiling: an IMI-RHAPSODY Study
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Li, Shiying, primary, Dragan, Iulian, additional, Fung, Chun Ho, additional, Kuznetsov, Dmitry, additional, Hansen, Michael K., additional, Beulens, Joline W.J., additional, ’t Hart, Leen M., additional, Slieker, Roderick C., additional, Donnelly, Louise A., additional, Gerl, Mathias J., additional, Klose, Christian, additional, Mehl, Florence, additional, Simons, Kai, additional, Elders, Petra JM, additional, Pearson, Ewan R., additional, Rutter, Guy A., additional, and Ibberson, Mark, additional
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- 2022
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39. Additional file 4 of Diabetes risk loci-associated pathways are shared across metabolic tissues
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Bouland, Gerard A., Beulens, Joline W. J., Nap, Joey, van der Slik, Arno R., Zaldumbide, Arnaud, ’t Hart, Leen M., and Slieker, Roderick C.
- Subjects
animal diseases ,fungi ,genetic processes ,food and beverages - Abstract
Additional file 4: Table S3. Protein, metabolite and expression QTLs associated with rs1260326.
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- 2022
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40. Additional file 5 of Diabetes risk loci-associated pathways are shared across metabolic tissues
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Bouland, Gerard A., Beulens, Joline W. J., Nap, Joey, van der Slik, Arno R., Zaldumbide, Arnaud, ’t Hart, Leen M., and Slieker, Roderick C.
- Subjects
animal diseases ,fungi ,genetic processes ,food and beverages - Abstract
Additional file 5: Table S4. Protein and expression QTLs associated with rs474513.
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- 2022
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41. Additional file 2 of Diabetes risk loci-associated pathways are shared across metabolic tissues
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Bouland, Gerard A., Beulens, Joline W. J., Nap, Joey, van der Slik, Arno R., Zaldumbide, Arnaud, ’t Hart, Leen M., and Slieker, Roderick C.
- Abstract
Additional file 2: Table S1. Characteristics of the individuals in the GTEX data.
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- 2022
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42. Additional file 1 of Diabetes risk loci-associated pathways are shared across metabolic tissues
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Bouland, Gerard A., Beulens, Joline W. J., Nap, Joey, van der Slik, Arno R., Zaldumbide, Arnaud, ’t Hart, Leen M., and Slieker, Roderick C.
- Abstract
Additional file 1: Figure S1. a Frequency of tissues in which a certain eGene was identified. X-axis, genes under influence of a diabetes SNP, y-axis, frequency of tissues in which the QTL was identified. Figure S2. Scatterplot of expression of RP11-613D13.10 versus the expression of HSD17B12. X-axis, expression of RP11-613D13.10; y-axis expression of HSD17B12. Figure S3. a Frequency of the number of times an enriched pathway was found across the twelve tested tissues. X-axis, pathway investigated; y-axis, frequency of tissues. Blue bars indicate pathways associated with HLA-genes. Figure S4. Relation between KEGG pathways identified in each of the tissues. Tissues include subcutaneous fat (a), visceral fat (b), sigmoid colon (c), transverse colon (d), pituitary (e), small intestine (f), stomach (g), thyroid (h), whole blood (i). Figure S5. Chromatin state segmentations for rs601945 in various tissues and cell lines (data from Epigenomics Roadmap). Plus-symbol indicates a SNP in LD and blood cell types are colored in blue. X-axis, location on the genome; y-axis cell type.
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- 2022
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43. Plasma protein N-glycosylation is associated with cardiovascular disease, nephropathy, and retinopathy in type 2 diabetes
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Memarian, Elham, primary, 't Hart, Leen M, additional, Slieker, Roderick C, additional, Lemmers, Roosmarijn F L, additional, van der Heijden, Amber A, additional, Rutters, Femke, additional, Nijpels, Giel, additional, Schoep, Emma, additional, Lieverse, Aloysius G, additional, Sijbrands, Eric J G, additional, Wuhrer, Manfred, additional, van Hoek, Mandy, additional, and Dotz, Viktoria, additional
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- 2021
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44. Performance of prediction models for nephropathy in people with type 2 diabetes: systematic review and external validation study
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Slieker, Roderick C, primary, van der Heijden, Amber A W A, additional, Siddiqui, Moneeza K, additional, Langendoen-Gort, Marlous, additional, Nijpels, Giel, additional, Herings, Ron, additional, Feenstra, Talitha L, additional, Moons, Karel G M, additional, Bell, Samira, additional, Elders, Petra J, additional, ’t Hart, Leen M, additional, and Beulens, Joline W J, additional
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- 2021
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45. The power of genetic diversity in genome-wide association studies of lipids
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Graham, Sarah E. Clarke, Shoa L. Wu, Kuan-Han H. Kanoni, Stavroula Zajac, Greg J. M. Ramdas, Shweta Surakka, Ida and Ntalla, Ioanna Vedantam, Sailaja Winkler, Thomas W. Locke, Adam E. Marouli, Eirini Hwang, Mi Yeong Han, Sohee and Narita, Akira Choudhury, Ananyo Bentley, Amy R. Ekoru, Kenneth Verma, Anurag Trivedi, Bhavi Martin, Hilary C. and Hunt, Karen A. Hui, Qin Klarin, Derek Zhu, Xiang and Thorleifsson, Gudmar Helgadottir, Anna Gudbjartsson, Daniel F. and Holm, Hilma Olafsson, Isleifur Akiyama, Masato Sakaue, Saori Terao, Chikashi Kanai, Masahiro Zhou, Wei and Brumpton, Ben M. Rasheed, Humaira Ruotsalainen, Sanni E. and Havulinna, Aki S. Veturi, Yogasudha Feng, QiPing Rosenthal, Elisabeth A. Lingren, Todd Pacheco, Jennifer Allen and Pendergrass, Sarah A. Haessler, Jeffrey Giulianini, Franco and Bradford, Yuki Miller, Jason E. Campbell, Archie Lin, Kuang and Millwood, Iona Y. Hindy, George Rasheed, Asif Faul, Jessica D. Zhao, Wei Weir, David R. Turman, Constance and Huang, Hongyan Graff, Mariaelisa Mahajan, Anubha Brown, Michael R. Zhang, Weihua Yu, Ketian Schmidt, Ellen M. and Pandit, Anita Gustafsson, Stefan Yin, Xianyong Luan, Jian'an and Zhao, Jing-Hua Matsuda, Fumihiko Jang, Hye-Mi Yoon, Kyungheon Medina-Gomez, Carolina Pitsillides, Achilleas and Hottenga, Jouke Jan Willemsen, Gonneke Wood, Andrew R. Ji, Yingji Gao, Zishan Haworth, Simon Mitchell, Ruth E. and Chai, Jin Fang Aadahl, Mette Yao, Jie Manichaikul, Ani and Warren, Helen R. Ramirez, Julia Bork-Jensen, Jette Karhus, Line L. Goel, Anuj Sabater-Lleal, Maria Noordam, Raymond and Sidore, Carlo Fiorillo, Edoardo McDaid, Aaron F. and Marques-Vidal, Pedro Wielscher, Matthias Trompet, Stella and Sattar, Naveed Mollehave, Line T. Thuesen, Betina H. Munz, Matthias Zeng, Lingyao Huang, Jianfeng Yang, Bin Poveda, Alaitz Kurbasic, Azra Lamina, Claudia Forer, Lukas and Scholz, Markus Galesloot, Tessel E. Bradfield, Jonathan P. and Daw, E. Warwick Zmuda, Joseph M. Mitchell, Jonathan S. and Fuchsberger, Christian Christensen, Henry Brody, Jennifer A. and Feitosa, Mary F. Wojczynski, Mary K. Preuss, Michael and Mangino, Massimo Christofidou, Paraskevi Verweij, Niek and Benjamins, Jan W. Engmann, Jorgen Kember, Rachel L. Slieker, Roderick C. Lo, Ken Sin Zilhao, Nuno R. Phuong Le and Kleber, Marcus E. Delgado, Graciela E. Huo, Shaofeng Ikeda, Daisuke D. Iha, Hiroyuki Yang, Jian Liu, Jun Leonard, Hampton L. Marten, Jonathan Schmidt, Borge Arendt, Marina and Smyth, Laura J. Canadas-Garre, Marisa Wang, Chaolong and Nakatochi, Masahiro Wong, Andrew Hutri-Kahonen, Nina Sim, Xueling Xia, Rui Huerta-Chagoya, Alicia Fernandez-Lopez, Juan Carlos Lyssenko, Valeriya Ahmed, Meraj Jackson, Anne U. and Irvin, Marguerite R. Oldmeadow, Christopher Kim, Han-Na and Ryu, Seungho Timmers, Paul R. H. J. Arbeeva, Liubov Dorajoo, Rajkumar Lange, Leslie A. Chai, Xiaoran Prasad, Gauri and Lores-Motta, Laura Pauper, Marc Long, Jirong Li, Xiaohui and Theusch, Elizabeth Takeuchi, Fumihiko Spracklen, Cassandra N. and Loukola, Anu Bollepalli, Sailalitha Warner, Sophie C. and Wang, Ya Xing Wei, Wen B. Nutile, Teresa Ruggiero, Daniela and Sung, Yun Ju Hung, Yi-Jen Chen, Shufeng Liu, Fangchao and Yang, Jingyun Kentistou, Katherine A. Gorski, Mathias and Brumat, Marco Meidtner, Karina Bielak, Lawrence F. Smith, Jennifer A. Hebbar, Prashantha Farmaki, Aliki-Eleni Hofer, Edith Lin, Maoxuan Xue, Chao Zhang, Jifeng Concas, Maria Pina Vaccargiu, Simona van der Most, Peter J. Pitkanen, Niina Cade, Brian E. Lee, Jiwon van Der Laan, Sander W. and Chitrala, Kumaraswamy Naidu Weiss, Stefan Zimmermann, Martina E. and Lee, Jong Young Choi, Hyeok Sun Nethander, Maria and Freitag-Wolf, Sandra Southam, Lorraine Rayner, Nigel W. and Wang, Carol A. Lin, Shih-Yi Wang, Jun-Sing Couture, Christian Lyytikainen, Leo-Pekka Nikus, Kjell and Cuellar-Partida, Gabriel Vestergaard, Henrik Hildalgo, Bertha and Giannakopoulou, Olga Cai, Qiuyin Obura, Morgan O. van Setten, Jessica Li, Xiaoyin Schwander, Karen Terzikhan, Natalie Shin, Jae Hun Jackson, Rebecca D. Reiner, Alexander P. Martin, Lisa Warsinger Chen, Zhengming Li, Liming and Highland, Heather M. Young, Kristin L. Kawaguchi, Takahisa and Thiery, Joachim Bis, Joshua C. Nadkarni, Girish N. Launer, Lenore J. Li, Huaixing Nalls, Mike A. Raitakari, Olli T. and Ichihara, Sahoko Wild, Sarah H. Nelson, Christopher P. and Campbell, Harry Jager, Susanne Nabika, Toru Al-Mulla, Fahd and Niinikoski, Harri Braund, Peter S. Kolcic, Ivana Kovacs, Peter Giardoglou, Tota Katsuya, Tomohiro Bhatti, Fatima and de Kleijn, Dominique de Borst, Gert J. Kim, Eung Kweon and Adams, Hieab H. H. Ikram, M. Arfan Zhu, Xiaofeng Asselbergs, Folkert W. Kraaijeveld, Adriaan O. Beulens, Joline W. J. and Shu, Xiao-Ou Rallidis, Loukianos S. Pedersen, Oluf Hansen, Torben Mitchell, Paul Hewitt, Alex W. Kahonen, Mika and Perusse, Louis Bouchard, Claude Tonjes, Anke Chen, Yii-Der Ida Pennell, Craig E. Mori, Trevor A. Lieb, Wolfgang and Franke, Andre Ohlsson, Claes Mellstrom, Dan Cho, Yoon Shin and Lee, Hyejin Yuan, Jian-Min Koh, Woon-Puay Rhee, Sang Youl Woo, Jeong-Taek Heid, Iris M. Stark, Klaus J. and Volzke, Henry Homuth, Georg Evans, Michele K. Zonderman, Alan B. Polasek, Ozren Pasterkamp, Gerard Hoefer, Imo E. and Redline, Susan Pahkala, Katja Oldehinkel, Albertine J. and Snieder, Harold Biino, Ginevra Schmidt, Reinhold Schmidt, Helena Chen, Y. Eugene Bandinelli, Stefania Dedoussis, George Thanaraj, Thangavel Alphonse Kardia, Sharon L. R. and Kato, Norihiro Schulze, Matthias B. Girotto, Giorgia Jung, Bettina Boger, Carsten A. Joshi, Peter K. Bennett, David A. and De Jager, Philip L. Lu, Xiangfeng Mamakou, Vasiliki and Brown, Morris Caulfield, Mark J. Munroe, Patricia B. Guo, Xiuqing Ciullo, Marina Jonas, Jost B. Samani, Nilesh J. and Kaprio, Jaakko Pajukanta, Paivi Adair, Linda S. Bechayda, Sonny Augustin de Silva, H. Janaka Wickremasinghe, Ananda R. and Krauss, Ronald M. Wu, Jer-Yuarn Zheng, Wei den Hollander, I, Anneke Bharadwaj, Dwaipayan Correa, Adolfo Wilson, James G. and Lind, Lars Heng, Chew-Kiat Nelson, Amanda E. Golightly, Yvonne M. Wilson, James F. Penninx, Brenda Kim, Hyung-Lae and Attia, John Scott, Rodney J. Rao, D. C. Arnett, Donna K. and Walker, Mark Koistinen, Heikki A. Chandak, Giriraj R. and Yajnik, Chittaranjan S. Mercader, Josep M. Tusie-Luna, Teresa and Aguilar-Salinas, Carlos A. Villalpando, Clicerio Gonzalez and Orozco, Lorena Fornage, Myriam Tai, E. Shyong van Dam, Rob M. Lehtimaki, Terho Chaturvedi, Nish Yokota, Mitsuhiro and Liu, Jianjun Reilly, Dermot F. McKnight, Amy Jayne Kee, Frank Jockel, Karl-Heinz McCarthy, I, Mark Palmer, Colin N. A. Vitart, Veronique Hayward, Caroline Simonsick, Eleanor and van Duijn, Cornelia M. Lu, Fan Qu, Jia Hishigaki, Haretsugu Lin, Xu Marz, Winfried Parra, Esteban J. Cruz, Miguel Gudnason, Vilmundur Tardif, Jean-Claude Lettre, Guillaume `t Hart, Leen M. Elders, Petra J. M. Damrauer, Scott M. Kumari, Meena Kivimaki, Mika van der Harst, Pim and Spector, Tim D. Loos, Ruth J. F. Province, Michael A. Psaty, Bruce M. Brandslund, Ivan Pramstaller, Peter P. Christensen, Kaare Ripatti, Samuli Widen, Elisabeth Hakonarson, Hakon and Grant, Struan F. A. Kiemeney, Lambertus A. L. M. de Graaf, Jacqueline Loeffler, Markus Kronenberg, Florian Gu, Dongfeng and Erdmann, Jeanette Schunkert, Heribert Franks, Paul W. and Linneberg, Allan Jukema, J. Wouter Khera, V, Amit Mannikko, Minna Jarvelin, Marjo-Riitta Kutalik, Zoltan Cucca, Francesco Mook-Kanamori, Dennis O. van Dijk, Ko Willems and Watkins, Hugh Strachan, David P. Grarup, Niels Sever, Peter and Poulter, Neil Rotter, I, Jerome Dantoft, Thomas M. and Karpe, Fredrik Neville, Matt J. Timpson, Nicholas J. Cheng, Ching-Yu Wong, Tien-Yin Khor, Chiea Chuen Sabanayagam, Charumathi Peters, Annette Gieger, Christian Hattersley, Andrew T. Pedersen, Nancy L. Magnusson, Patrik K. E. and Boomsma, I, Dorret de Geus, Eco J. C. Cupples, L. Adrienne and van Meurs, Joyce B. J. Ghanbari, Mohsen Rsen, Penny Gordon-La and Huang, Wei Kim, Young Jin Tabara, Yasuharu Wareham, Nicholas J. Langenberg, Claudia Zeggini, Eleftheria and Kuusisto, Johanna Laakso, Markku Ingelsson, Erik Abecasis, Goncalo Chambers, John C. Kooner, Jaspal S. de Vries, Paul S. Morrison, Alanna C. North, Kari E. Daviglus, Martha and Kraft, Peter Martin, Nicholas G. Whitfield, John B. Abbas, Shahid Saleheen, Danish Walters, Robin G. Holmes, V, Michael and Black, Corri Smith, Blair H. Justice, Anne E. Baras, Aris Buring, Julie E. Ridker, Paul M. Chasman, I, Daniel and Kooperberg, Charles Wei, Wei-Qi Jarvik, Gail P. Namjou, Bahram Hayes, M. Geoffrey Ritchie, Marylyn D. Jousilahti, Pekka Salomaa, Veikko Hveem, Kristian Asvold, Bjorn Olav and Kubo, Michiaki Kamatani, Yoichiro Okada, Yukinori Murakami, Yoshinori Thorsteinsdottir, Unnur Stefansson, Kari Ho, Yuk-Lam Lynch, Julie A. Rader, Daniel J. Tsao, Philip S. and Chang, Kyong-Mi Cho, Kelly O'Donnell, Christopher J. and Gaziano, John M. Wilson, Peter Rotimi, Charles N. and Hazelhurst, Scott Ramsay, Michele Trembath, Richard C. van Heel, David A. Tamiya, Gen Yamamoto, Masayuki Kim, Bong-Jo and Mohlke, Karen L. Frayling, Timothy M. Hirschhorn, Joel N. and Kathiresan, Sekar Boehnke, Michael Natarajan, Pradeep and Peloso, Gina M. Brown, Christopher D. Morris, Andrew P. and Assimes, Themistocles L. Deloukas, Panos Sun, V, Yan Willer, Cristen J.
- Abstract
Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use(1). Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels(2), heart disease remains the leading cause of death worldwide(3). Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS(4-23) have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns(24). Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine(25), we anticipate that increased diversity of participants will lead to more accurate and equitable(26) application of polygenic scores in clinical practice.
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- 2021
46. Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes: An IMI-RHAPSODY Study
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Slieker, Roderick C., primary, Donnelly, Louise A., additional, Fitipaldi, Hugo, additional, Bouland, Gerard A., additional, Giordano, Giuseppe N., additional, Åkerlund, Mikael, additional, Gerl, Mathias J., additional, Ahlqvist, Emma, additional, Ali, Ashfaq, additional, Dragan, Iulian, additional, Elders, Petra, additional, Festa, Andreas, additional, Hansen, Michael K., additional, van der Heijden, Amber A., additional, Mansour Aly, Dina, additional, Kim, Min, additional, Kuznetsov, Dmitry, additional, Mehl, Florence, additional, Klose, Christian, additional, Simons, Kai, additional, Pavo, Imre, additional, Pullen, Timothy J., additional, Suvitaival, Tommi, additional, Wretlind, Asger, additional, Rossing, Peter, additional, Lyssenko, Valeriya, additional, Legido Quigley, Cristina, additional, Groop, Leif, additional, Thorens, Bernard, additional, Franks, Paul W., additional, Ibberson, Mark, additional, Rutter, Guy A., additional, Beulens, Joline W.J., additional, ’t Hart, Leen M., additional, and Pearson, Ewan R., additional
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- 2021
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47. Long RNA Sequencing and Ribosome Profiling of Inflamed β-Cells Reveal an Extensive Translatome Landscape
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Thomaidou, Sofia, primary, Slieker, Roderick C., additional, van der Slik, Arno R., additional, Boom, Jasper, additional, Mulder, Flip, additional, Munoz-Garcia, Amadeo, additional, ‘t Hart, Leen M., additional, Koeleman, Bobby, additional, Carlotti, Françoise, additional, Hoeben, Rob C., additional, Roep, Bart O., additional, Mei, Hailiang, additional, and Zaldumbide, Arnaud, additional
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- 2021
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48. Replication and cross-validation of type 2 diabetes subtypes based on clinical variables:an IMI-RHAPSODY study
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Slieker, Roderick C., Donnelly, Louise A, Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J, Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Festa, Andreas, Hansen, Michael K., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J, Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido-Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A, Beulens, Joline W J, ‘t Hart, Leen M, Pearson, Ewan R, Slieker, Roderick C., Donnelly, Louise A, Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J, Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Festa, Andreas, Hansen, Michael K., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J, Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido-Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A, Beulens, Joline W J, ‘t Hart, Leen M, and Pearson, Ewan R
- Abstract
Aims/hypothesis: Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes. In the current study we replicate and cross-validate these type 2 diabetes clusters in three large cohorts using variables readily measured in the clinic. Methods: In three independent cohorts, in total 15,940 individuals were clustered based on age, BMI, HbA1c, random or fasting C-peptide, and HDL-cholesterol. Clusters were cross-validated against the original clusters based on HOMA measures. In addition, between cohorts, clusters were cross-validated by re-assigning people based on each cohort’s cluster centres. Finally, we compared the time to insulin requirement for each cluster. Results: Five distinct type 2 diabetes clusters were identified and mapped back to the original four All New Diabetics in Scania (ANDIS) clusters. Using C-peptide and HDL-cholesterol instead of HOMA2-B and HOMA2-IR, three of the clusters mapped with high sensitivity (80.6–90.7%) to the previously identified severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) clusters. The previously described ANDIS mild age-related diabetes (MARD) cluster could be mapped to the two milder groups in our study: one characterised by high HDL-cholesterol (mild diabetes with high HDL-cholesterol [MDH] cluster), and the other not having any extreme characteristic (mild diabetes [MD]). When these two milder groups were combined, they mapped well to the previously labelled MARD cluster (sensitivity 79.1%). In the cross-validation between cohorts, particularly the SIDD and MDH clusters cross-validated well, with sensitivities ranging from 73.3% to 97.1%. SIRD and MD showed a lower sensitivity, ranging from 36.1% to 92.3%, where individuals shifted from SIRD to MD and vice versa. People belonging to the SIDD cluster showed the fastest progression towards insulin requiremen
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- 2021
49. Distinct Molecular Signatures of Clinical Clusters in People With Type 2 Diabetes:An IMI-RHAPSODY Study
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Slieker, Roderick C., Donnelly, Louise A., Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J., Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Elders, Petra, Festa, Andreas, Hansen, Michael K., van der Heijden, Amber A., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J., Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A., Beulens, Joline W.J., 't Hart, Leen M., Pearson, Ewan R., Slieker, Roderick C., Donnelly, Louise A., Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J., Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Elders, Petra, Festa, Andreas, Hansen, Michael K., van der Heijden, Amber A., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J., Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A., Beulens, Joline W.J., 't Hart, Leen M., and Pearson, Ewan R.
- Abstract
Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity, investigators of a previous study clustered people with diabetes according to five diabetes subtypes. The aim of the current study is to investigate the etiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic (N = 12,828), metabolomic (N = 2,945), lipidomic (N = 2,593), and proteomic (N = 1,170) data were obtained in plasma. For each data type, each cluster was compared with the other four clusters as the reference. The insulin-resistant cluster showed the most distinct molecular signature, with higher branched-chain amino acid, diacylglycerol, and triacylglycerol levels and aberrant protein levels in plasma were enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher levels of cytokines. The mild diabetes cluster with high HDL showed the most beneficial molecular profile with effects opposite of those seen in the insulin-resistant cluster. This study shows that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease.
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- 2021
50. Processes Underlying Glycemic Deterioration in Type 2 Diabetes:An IMI DIRECT Study
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Bizzotto, Roberto, Jennison, Christopher, Jones, Angus G., Kurbasic, Azra, Tura, Andrea, Kennedy, Gwen, Bell, Jimmy D., Thomas, E. Louise, Frost, Gary, Eriksen, Rebeca, Koivula, Robert W., Brage, Soren, Kaye, Jane, Hattersley, Andrew T., Heggie, Alison, McEvoy, Donna, 't Hart, Leen M., Beulens, Joline W., Elders, Petra, Musholt, Petra B., Ridderstrale, Martin, Hansen, Tue H., Allin, Kristine H., Hansen, Torben, Vestergaard, Henrik, Lundgaard, Agnete T., Thomsen, Henrik S., De Masi, Federico, Tsirigos, Konstantinos D., Brunak, Søren, Vinuela, Ana, Mahajan, Anubha, McDonald, Timothy J., Kokkola, Tarja, Forgie, Ian M., Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil, McCarthy, Mark I., Pedersen, Oluf, Schwenk, Jochen M., Adamski, Jerzy, Franks, Paul W., Walker, Mark, Pearson, Ewan R., Mari, Andrea, Bizzotto, Roberto, Jennison, Christopher, Jones, Angus G., Kurbasic, Azra, Tura, Andrea, Kennedy, Gwen, Bell, Jimmy D., Thomas, E. Louise, Frost, Gary, Eriksen, Rebeca, Koivula, Robert W., Brage, Soren, Kaye, Jane, Hattersley, Andrew T., Heggie, Alison, McEvoy, Donna, 't Hart, Leen M., Beulens, Joline W., Elders, Petra, Musholt, Petra B., Ridderstrale, Martin, Hansen, Tue H., Allin, Kristine H., Hansen, Torben, Vestergaard, Henrik, Lundgaard, Agnete T., Thomsen, Henrik S., De Masi, Federico, Tsirigos, Konstantinos D., Brunak, Søren, Vinuela, Ana, Mahajan, Anubha, McDonald, Timothy J., Kokkola, Tarja, Forgie, Ian M., Giordano, Giuseppe N., Pavo, Imre, Ruetten, Hartmut, Dermitzakis, Emmanouil, McCarthy, Mark I., Pedersen, Oluf, Schwenk, Jochen M., Adamski, Jerzy, Franks, Paul W., Walker, Mark, Pearson, Ewan R., and Mari, Andrea
- Abstract
OBJECTIVEWe investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSA total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), beta-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA(1c) deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression.RESULTSFaster HbA(1c) progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R-2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role.CONCLUSIONSDeteriorating insulin sensitivity and beta-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, beta-cell function, and insulin clearance may be relevant to prevent
- Published
- 2021
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