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1
The Trans-Ancestral Genomic Architecture of Glycemic Traits
Chen, Ji
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Spracklen, Cassandra N.
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Marenne, Gaëlle
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Varshney, Arushi
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Corbin, Laura J
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Luan, Jian’an
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Willems, Sara M
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Wu, Ying
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Zhang, Xiaoshuai
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Horikoshi, Momoko
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Boutin, Thibaud S
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Mägi, Reedik
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Waage, Johannes
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Pitsilides, Achilleas
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Li-Gao, Ruifang
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Chan, Kei Hang Katie
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Yao, Jie
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Anasanti, Mila D
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Chu, Audrey Y
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Claringbould, Annique
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Heikkinen, Jani
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Hong, Jaeyoung
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Hottenga, Jouke-Jan
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Huo, Shaofeng
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Kaakinen, Marika A.
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Louie, Tin
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März, Winfried
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Moreno-Macias, Hortensia
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Ndungu, Anne
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Nelson, Sarah C.
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Nolte, Ilja M.
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North, Kari E
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Raulerson, Chelsea K.
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Ray, Debashree
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Rohde, Rebecca
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Rybin, Denis
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Schurmann, Claudia
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Sim, Xueling
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Southam, Loz
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Stewart, Isobel D
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Wang, Carol A.
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Wang, Yujie
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Wu, Peitao
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Zhang, Weihua
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Ahluwalia, Tarunveer S.
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Appel, Emil VR
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Bielak, Lawrence F.
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Brody, Jennifer A.
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Burtt, Noël P
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Cabrera, Claudia P
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Cade, Brian E
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Chai, Jin Fang
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Chai, Xiaoran
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Chang, Li-Ching
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Chen, Chien-Hsiun
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Chen, Brian H
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Chitrala, Kumaraswamy Naidu
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Chiu, Yen-Feng
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de Haan, Hugoline G.
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Delgado, Graciela E
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Demirkan, Ayse
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Duan, Qing
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Engmann, Jorgen
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Fatumo, Segun A
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Gayán, Javier
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Giulianini, Franco
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Gong, Jung Ho
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Gustafsson, Stefan
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Hai, Yang
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Hartwig, Fernando P
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He, Jing
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Heianza, Yoriko
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Huang, Tao
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Huerta-Chagoya, Alicia
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Hwang, Mi Yeong
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Jensen, Richard A.
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Kawaguchi, Takahisa
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Kentistou, Katherine A
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Kim, Young Jin
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Kleber, Marcus E
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Kooner, Ishminder K
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Lai, Shuiqing
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Lange, Leslie A
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Langefeld, Carl D
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Lauzon, Marie
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Li, Man
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Ligthart, Symen
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Liu, Jun
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Loh, Marie
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Long, Jirong
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Lyssenko, Valeriya
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Mangino, Massimo
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Marzi, Carola
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Montasser, May E
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Nag, Abhishek
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Nakatochi, Masahiro
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Noce, Damia
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Noordam, Raymond
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Pistis, Giorgio
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Preuss, Michael
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Raffield, Laura
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Rasmussen-Torvik, Laura J.
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Rich, Stephen S
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Robertson, Neil R
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Rueedi, Rico
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Ryan, Kathleen
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Sanna, Serena
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Saxena, Richa
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Schraut, Katharina E
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Sennblad, Bengt
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Setoh, Kazuya
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Smith, Albert V
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Southam, Lorraine
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Sparsø, Thomas
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Strawbridge, Rona J
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Takeuchi, Fumihiko
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Tan, Jingyi
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Trompet, Stella
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van den Akker, Erik
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van der Most, Peter J
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Verweij, Niek
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Vogel, Mandy
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Wang, Heming
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Wang, Chaolong
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Wang, Nan
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Warren, Helen R
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Wen, Wanqing
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Wilsgaard, Tom
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Wong, Andrew
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Wood, Andrew R
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Xie, Tian
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Zafarmand, Mohammad Hadi
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Zhao, Jing-Hua
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Zhao, Wei
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Amin, Najaf
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Arzumanyan, Zorayr
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Astrup, Arne
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Bakker, Stephan JL
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Baldassarre, Damiano
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Beekman, Marian
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Bergman, Richard N
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Bertoni, Alain
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Blüher, Matthias
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Bonnycastle, Lori L.
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Bornstein, Stefan R
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Bowden, Donald W
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Cai, Qiuyin
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Campbell, Archie
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Campbell, Harry
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Chang, Yi Cheng
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de Geus, Eco J.C.
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Dehghan, Abbas
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Du, Shufa
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Eiriksdottir, Gudny
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Farmaki, Aliki Eleni
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Frånberg, Mattias
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Fuchsberger, Christian
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Gao, Yutang
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Gjesing, Anette P
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Goel, Anuj
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Han, Sohee
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Hartman, Catharina A
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Herder, Christian
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Hicks, Andrew A.
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Hsieh, Chang-Hsun
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Hsueh, Willa A.
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Ichihara, Sahoko
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Igase, Michiya
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Ikram, M. Arfan
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Johnson, W. Craig
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Jørgensen, Marit E
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Joshi, Peter K
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Kalyani, Rita R
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Kandeel, Fouad R.
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Katsuya, Tomohiro
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Khor, Chiea Chuen
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Kiess, Wieland
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Kolcic, Ivana
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Kuulasmaa, Teemu
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Kuusisto, Johanna
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Läll, Kristi
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Lam, Kelvin
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Lawlor, Deborah A
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Lee, Nanette R.
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Lemaitre, Rozenn N.
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Li, Honglan
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Study, Lifelines Cohort
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Lin, Shih-Yi
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Lindström, Jaana
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Linneberg, Allan
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Liu, Jianjun
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Lorenzo, Carlos
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Matsubara, Tatsuaki
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Matsuda, Fumihiko
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Mingrone, Geltrude
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Mooijaart, Simon
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Moon, Sanghoon
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Nabika, Toru
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Nadkarni, Girish N.
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Nadler, Jerry L.
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Nelis, Mari
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Neville, Matt J
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Norris, Jill M
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Ohyagi, Yasumasa
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Peters, Annette
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Peyser, Patricia A.
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Polasek, Ozren
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Qi, Qibin
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Raven, Dennis
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Reilly, Dermot F
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Reiner, Alex
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Rivideneira, Fernando
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Roll, Kathryn
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Rudan, Igor
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Sabanayagam, Charumathi
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Sandow, Kevin
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Sattar, Naveed
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Schürmann, Annette
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Shi, Jinxiu
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Stringham, Heather M
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Taylor, Kent D.
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Teslovich, Tanya M.
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Thuesen, Betina
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Timmers, Paul RHJ
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Tremoli, Elena
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Tsai, Michael Y
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Uitterlinden, Andre
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van Dam, Rob M
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van Heemst, Diana
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van Hylckama Vlieg, Astrid
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Van Vliet-Ostaptchouk, Jana V
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Vangipurapu, Jagadish
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Vestergaard, Henrik
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Wang, Tao
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van Dijk, Ko Willems
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Zemunik, Tatijana
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Abecasis, Goncalo R
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Adair, Linda S.
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Aguilar-Salinas, Carlos Alberto
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Alarcón-Riquelme, Marta E
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An, Ping
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Aviles-Santa, Larissa
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Becker, Diane M
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Beilin, Lawrence J
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Bergmann, Sven
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Bisgaard, Hans
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Black, Corri
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Boehnke, Michael
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Boerwinkle, Eric
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Böhm, Bernhard O
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Bønnelykke, Klaus
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Boomsma, D I.
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Bottinger, Erwin P.
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Buchanan, Thomas A
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Canouil, Mickaël
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Caulfield, Mark J
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Chambers, John C.
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Chasman, Daniel I.
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Chen, Yii-Der Ida
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Cheng, Ching-Yu
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Collins, Francis S.
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Correa, Adolfo
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Cucca, Francesco
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de Silva, H. Janaka
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Dedoussis, George
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Elmståhl, Sölve
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Evans, Michele K.
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Ferrannini, Ele
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Ferrucci, Luigi
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Florez, Jose C
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Franks, Paul W
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Frayling, Timothy M
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Froguel, Philippe
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Gigante, Bruna
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Goodarzi, Mark O.
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Gordon-Larsen, Penny
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Grallert, Harald
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Grarup, Niels
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Grimsgaard, Sameline
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Groop, Leif
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Gudnason, Vilmundur
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Guo, Xiuqing
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Hamsten, Anders
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Hansen, Torben
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Hayward, Caroline
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Heckbert, Susan R.
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Horta, Bernardo L
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Huang, Wei
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Ingelsson, Erik
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James, Pankow S
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Jarvelin, Marjo-Ritta
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Jonas, Jost B
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Jukema, J. Wouter
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Kaleebu, Pontiano
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Kaplan, Robert
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Kardia, Sharon L.R.
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Kato, Norihiro
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Keinanen-Kiukaanniemi, Sirkka M.
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Kim, Bong-Jo
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Kivimaki, Mika
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Koistinen, Heikki A.
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Kooner, Jaspal S.
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Körner, Antje
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Kovacs, Peter
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Kuh, Diana
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Kumari, Meena
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Kutalik, Zoltan
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Laakso, Markku
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Lakka, Timo A.
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Launer, Lenore J
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Leander, Karin
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Li, Huaixing
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Lin, Xu
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Lind, Lars
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Lindgren, Cecilia
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Liu, Simin
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Loos, Ruth J.F.
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Magnusson, Patrik KE
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Mahajan, Anubha
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Metspalu, Andres
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Mook-Kanamori, Dennis O
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Mori, Trevor A
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Munroe, Patricia B
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Njølstad, Inger
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O’Connell, Jeffrey R
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Oldehinkel, Albertine J
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Ong, Ken K
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Padmanabhan, Sandosh
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Palmer, Colin N.A.
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Palmer, Nicholette D
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Pedersen, Oluf
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Pennell, Craig E
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Porteous, David J
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Pramstaller, Peter P.
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Province, Michael A.
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Psaty, Bruce M.
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Qi, Lu
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Raffel, Leslie J.
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Rauramaa, Rainer
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Redline, Susan
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Ridker, Paul M
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Rosendaal, Frits R.
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Saaristo, Timo E.
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Sandhu, Manjinder
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Saramies, Jouko
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Schneiderman, Neil
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Schwarz, Peter
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Scott, Laura J.
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Selvin, Elizabeth
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Sever, Peter
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Shu, Xiao-ou
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Slagboom, P Eline
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Small, Kerrin S
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Smith, Blair H
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Snieder, Harold
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Sofer, Tamar
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Sørensen, Thorkild I.A.
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Spector, Tim D
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Stanton, Alice
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Steves, Claire J
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Stumvoll, Michael
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Sun, Liang
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Tabara, Yasuharu
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Tai, E Shyong
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Timpson, Nicholas J
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Tönjes, Anke
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Tuomilehto, Jaakko
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Tusie, Teresa
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Uusitupa, Matti
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van der Harst, Pim
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van Duijn, Cornelia
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Vitart, Veronique
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Vollenweider, Peter
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Vrijkotte, Tanja GM
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Wagenknecht, Lynne E
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Walker, Mark
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Wang, Ya X
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Wareham, Nick J
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Watanabe, Richard M
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Watkins, Hugh
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Wei, Wen B
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Wickremasinghe, Ananda R
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Willemsen, Gonneke
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Wilson, James F
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Wong, Tien-Yin
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Wu, Jer-Yuarn
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Xiang, Anny H
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Yanek, Lisa R
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Yengo, Loïc
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Yokota, Mitsuhiro
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Zeggini, Eleftheria
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Zheng, Wei
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Zonderman, Alan B
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Rotter, Jerome I
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Gloyn, Anna L
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McCarthy, Mark I.
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Dupuis, Josée
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Meigs, James B
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Scott, Robert A
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Prokopenko, Inga
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Leong, Aaron
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Liu, Ching-Ti
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Parker, Stephen CJ
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Mohlke, Karen L.
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Langenberg, Claudia
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Wheeler, Eleanor
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Morris, Andrew P.
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Barroso, Inês
In: Nat Genet (2021)
Abstract:
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.
Keyword:
Article
URL:
http://www.ncbi.nlm.nih.gov/pubmed/34059833
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958/
https://doi.org/10.1038/s41588-021-00852-9
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