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The Trans-Ancestral Genomic Architecture of Glycemic Traits

Glycemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-...

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Detalles Bibliográficos
Autores principales: Chen, Ji, Spracklen, Cassandra N., Marenne, Gaëlle, Varshney, Arushi, Corbin, Laura J, Luan, Jian’an, Willems, Sara M, Wu, Ying, Zhang, Xiaoshuai, Horikoshi, Momoko, Boutin, Thibaud S, Mägi, Reedik, Waage, Johannes, Pitsilides, Achilleas, Li-Gao, Ruifang, Chan, Kei Hang Katie, Yao, Jie, Anasanti, Mila D, Chu, Audrey Y, Claringbould, Annique, Heikkinen, Jani, Hong, Jaeyoung, Hottenga, Jouke-Jan, Huo, Shaofeng, Kaakinen, Marika A., Louie, Tin, März, Winfried, Moreno-Macias, Hortensia, Ndungu, Anne, Nelson, Sarah C., Nolte, Ilja M., North, Kari E, Raulerson, Chelsea K., Ray, Debashree, Rohde, Rebecca, Rybin, Denis, Schurmann, Claudia, Sim, Xueling, Southam, Loz, Stewart, Isobel D, Wang, Carol A., Wang, Yujie, Wu, Peitao, Zhang, Weihua, Ahluwalia, Tarunveer S., Appel, Emil VR, Bielak, Lawrence F., Brody, Jennifer A., Burtt, Noël P, Cabrera, Claudia P, Cade, Brian E, Chai, Jin Fang, Chai, Xiaoran, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Brian H, Chitrala, Kumaraswamy Naidu, Chiu, Yen-Feng, de Haan, Hugoline G., Delgado, Graciela E, Demirkan, Ayse, Duan, Qing, Engmann, Jorgen, Fatumo, Segun A, Gayán, Javier, Giulianini, Franco, Gong, Jung Ho, Gustafsson, Stefan, Hai, Yang, Hartwig, Fernando P, He, Jing, Heianza, Yoriko, Huang, Tao, Huerta-Chagoya, Alicia, Hwang, Mi Yeong, Jensen, Richard A., Kawaguchi, Takahisa, Kentistou, Katherine A, Kim, Young Jin, Kleber, Marcus E, Kooner, Ishminder K, Lai, Shuiqing, Lange, Leslie A, Langefeld, Carl D, Lauzon, Marie, Li, Man, Ligthart, Symen, Liu, Jun, Loh, Marie, Long, Jirong, Lyssenko, Valeriya, Mangino, Massimo, Marzi, Carola, Montasser, May E, Nag, Abhishek, Nakatochi, Masahiro, Noce, Damia, Noordam, Raymond, Pistis, Giorgio, Preuss, Michael, Raffield, Laura, Rasmussen-Torvik, Laura J., Rich, Stephen S, Robertson, Neil R, Rueedi, Rico, Ryan, Kathleen, Sanna, Serena, Saxena, Richa, Schraut, Katharina E, Sennblad, Bengt, Setoh, Kazuya, Smith, Albert V, Southam, Lorraine, Sparsø, Thomas, Strawbridge, Rona J, Takeuchi, Fumihiko, Tan, Jingyi, Trompet, Stella, van den Akker, Erik, van der Most, Peter J, Verweij, Niek, Vogel, Mandy, Wang, Heming, Wang, Chaolong, Wang, Nan, Warren, Helen R, Wen, Wanqing, Wilsgaard, Tom, Wong, Andrew, Wood, Andrew R, Xie, Tian, Zafarmand, Mohammad Hadi, Zhao, Jing-Hua, Zhao, Wei, Amin, Najaf, Arzumanyan, Zorayr, Astrup, Arne, Bakker, Stephan JL, Baldassarre, Damiano, Beekman, Marian, Bergman, Richard N, Bertoni, Alain, Blüher, Matthias, Bonnycastle, Lori L., Bornstein, Stefan R, Bowden, Donald W, Cai, Qiuyin, Campbell, Archie, Campbell, Harry, Chang, Yi Cheng, de Geus, Eco J.C., Dehghan, Abbas, Du, Shufa, Eiriksdottir, Gudny, Farmaki, Aliki Eleni, Frånberg, Mattias, Fuchsberger, Christian, Gao, Yutang, Gjesing, Anette P, Goel, Anuj, Han, Sohee, Hartman, Catharina A, Herder, Christian, Hicks, Andrew A., Hsieh, Chang-Hsun, Hsueh, Willa A., Ichihara, Sahoko, Igase, Michiya, Ikram, M. Arfan, Johnson, W. Craig, Jørgensen, Marit E, Joshi, Peter K, Kalyani, Rita R, Kandeel, Fouad R., Katsuya, Tomohiro, Khor, Chiea Chuen, Kiess, Wieland, Kolcic, Ivana, Kuulasmaa, Teemu, Kuusisto, Johanna, Läll, Kristi, Lam, Kelvin, Lawlor, Deborah A, Lee, Nanette R., Lemaitre, Rozenn N., Li, Honglan, Study, Lifelines Cohort, Lin, Shih-Yi, Lindström, Jaana, Linneberg, Allan, Liu, Jianjun, Lorenzo, Carlos, Matsubara, Tatsuaki, Matsuda, Fumihiko, Mingrone, Geltrude, Mooijaart, Simon, Moon, Sanghoon, Nabika, Toru, Nadkarni, Girish N., Nadler, Jerry L., Nelis, Mari, Neville, Matt J, Norris, Jill M, Ohyagi, Yasumasa, Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Qi, Qibin, Raven, Dennis, Reilly, Dermot F, Reiner, Alex, Rivideneira, Fernando, Roll, Kathryn, Rudan, Igor, Sabanayagam, Charumathi, Sandow, Kevin, Sattar, Naveed, Schürmann, Annette, Shi, Jinxiu, Stringham, Heather M, Taylor, Kent D., Teslovich, Tanya M., Thuesen, Betina, Timmers, Paul RHJ, Tremoli, Elena, Tsai, Michael Y, Uitterlinden, Andre, van Dam, Rob M, van Heemst, Diana, van Hylckama Vlieg, Astrid, Van Vliet-Ostaptchouk, Jana V, Vangipurapu, Jagadish, Vestergaard, Henrik, Wang, Tao, van Dijk, Ko Willems, Zemunik, Tatijana, Abecasis, Goncalo R, Adair, Linda S., Aguilar-Salinas, Carlos Alberto, Alarcón-Riquelme, Marta E, An, Ping, Aviles-Santa, Larissa, Becker, Diane M, Beilin, Lawrence J, Bergmann, Sven, Bisgaard, Hans, Black, Corri, Boehnke, Michael, Boerwinkle, Eric, Böhm, Bernhard O, Bønnelykke, Klaus, Boomsma, D I., Bottinger, Erwin P., Buchanan, Thomas A, Canouil, Mickaël, Caulfield, Mark J, Chambers, John C., Chasman, Daniel I., Chen, Yii-Der Ida, Cheng, Ching-Yu, Collins, Francis S., Correa, Adolfo, Cucca, Francesco, de Silva, H. Janaka, Dedoussis, George, Elmståhl, Sölve, Evans, Michele K., Ferrannini, Ele, Ferrucci, Luigi, Florez, Jose C, Franks, Paul W, Frayling, Timothy M, Froguel, Philippe, Gigante, Bruna, Goodarzi, Mark O., Gordon-Larsen, Penny, Grallert, Harald, Grarup, Niels, Grimsgaard, Sameline, Groop, Leif, Gudnason, Vilmundur, Guo, Xiuqing, Hamsten, Anders, Hansen, Torben, Hayward, Caroline, Heckbert, Susan R., Horta, Bernardo L, Huang, Wei, Ingelsson, Erik, James, Pankow S, Jarvelin, Marjo-Ritta, Jonas, Jost B, Jukema, J. Wouter, Kaleebu, Pontiano, Kaplan, Robert, Kardia, Sharon L.R., Kato, Norihiro, Keinanen-Kiukaanniemi, Sirkka M., Kim, Bong-Jo, Kivimaki, Mika, Koistinen, Heikki A., Kooner, Jaspal S., Körner, Antje, Kovacs, Peter, Kuh, Diana, Kumari, Meena, Kutalik, Zoltan, Laakso, Markku, Lakka, Timo A., Launer, Lenore J, Leander, Karin, Li, Huaixing, Lin, Xu, Lind, Lars, Lindgren, Cecilia, Liu, Simin, Loos, Ruth J.F., Magnusson, Patrik KE, Mahajan, Anubha, Metspalu, Andres, Mook-Kanamori, Dennis O, Mori, Trevor A, Munroe, Patricia B, Njølstad, Inger, O’Connell, Jeffrey R, Oldehinkel, Albertine J, Ong, Ken K, Padmanabhan, Sandosh, Palmer, Colin N.A., Palmer, Nicholette D, Pedersen, Oluf, Pennell, Craig E, Porteous, David J, Pramstaller, Peter P., Province, Michael A., Psaty, Bruce M., Qi, Lu, Raffel, Leslie J., Rauramaa, Rainer, Redline, Susan, Ridker, Paul M, Rosendaal, Frits R., Saaristo, Timo E., Sandhu, Manjinder, Saramies, Jouko, Schneiderman, Neil, Schwarz, Peter, Scott, Laura J., Selvin, Elizabeth, Sever, Peter, Shu, Xiao-ou, Slagboom, P Eline, Small, Kerrin S, Smith, Blair H, Snieder, Harold, Sofer, Tamar, Sørensen, Thorkild I.A., Spector, Tim D, Stanton, Alice, Steves, Claire J, Stumvoll, Michael, Sun, Liang, Tabara, Yasuharu, Tai, E Shyong, Timpson, Nicholas J, Tönjes, Anke, Tuomilehto, Jaakko, Tusie, Teresa, Uusitupa, Matti, van der Harst, Pim, van Duijn, Cornelia, Vitart, Veronique, Vollenweider, Peter, Vrijkotte, Tanja GM, Wagenknecht, Lynne E, Walker, Mark, Wang, Ya X, Wareham, Nick J, Watanabe, Richard M, Watkins, Hugh, Wei, Wen B, Wickremasinghe, Ananda R, Willemsen, Gonneke, Wilson, James F, Wong, Tien-Yin, Wu, Jer-Yuarn, Xiang, Anny H, Yanek, Lisa R, Yengo, Loïc, Yokota, Mitsuhiro, Zeggini, Eleftheria, Zheng, Wei, Zonderman, Alan B, Rotter, Jerome I, Gloyn, Anna L, McCarthy, Mark I., Dupuis, Josée, Meigs, James B, Scott, Robert A, Prokopenko, Inga, Leong, Aaron, Liu, Ching-Ti, Parker, Stephen CJ, Mohlke, Karen L., Langenberg, Claudia, Wheeler, Eleanor, Morris, Andrew P., Barroso, Inês
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958/
https://www.ncbi.nlm.nih.gov/pubmed/34059833
http://dx.doi.org/10.1038/s41588-021-00852-9
Descripción
Sumario:Glycemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated hemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P<5x10(-8)), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.