RT Journal Article
SR Electronic
T1 A Low-Frequency Inactivating <em>AKT2</em> Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 2019
OP 2032
DO 10.2337/db16-1329
VO 66
IS 7
A1 Manning, Alisa
A1 Highland, Heather M.
A1 Gasser, Jessica
A1 Sim, Xueling
A1 Tukiainen, Taru
A1 Fontanillas, Pierre
A1 Grarup, Niels
A1 Rivas, Manuel A.
A1 Mahajan, Anubha
A1 Locke, Adam E.
A1 Cingolani, Pablo
A1 Pers, Tune H.
A1 Viñuela, Ana
A1 Brown, Andrew A.
A1 Wu, Ying
A1 Flannick, Jason
A1 Fuchsberger, Christian
A1 Gamazon, Eric R.
A1 Gaulton, Kyle J.
A1 Im, Hae Kyung
A1 Teslovich, Tanya M.
A1 Blackwell, Thomas W.
A1 Bork-Jensen, Jette
A1 Burtt, Noël P.
A1 Chen, Yuhui
A1 Green, Todd
A1 Hartl, Christopher
A1 Kang, Hyun Min
A1 Kumar, Ashish
A1 Ladenvall, Claes
A1 Ma, Clement
A1 Moutsianas, Loukas
A1 Pearson, Richard D.
A1 Perry, John R.B.
A1 Rayner, N. William
A1 Robertson, Neil R.
A1 Scott, Laura J.
A1 van de Bunt, Martijn
A1 Eriksson, Johan G.
A1 Jula, Antti
A1 Koskinen, Seppo
A1 Lehtimäki, Terho
A1 Palotie, Aarno
A1 Raitakari, Olli T.
A1 Jacobs, Suzanne B.R.
A1 Wessel, Jennifer
A1 Chu, Audrey Y.
A1 Scott, Robert A.
A1 Goodarzi, Mark O.
A1 Blancher, Christine
A1 Buck, Gemma
A1 Buck, David
A1 Chines, Peter S.
A1 Gabriel, Stacey
A1 Gjesing, Anette P.
A1 Groves, Christopher J.
A1 Hollensted, Mette
A1 Huyghe, Jeroen R.
A1 Jackson, Anne U.
A1 Jun, Goo
A1 Justesen, Johanne Marie
A1 Mangino, Massimo
A1 Murphy, Jacquelyn
A1 Neville, Matt
A1 Onofrio, Robert
A1 Small, Kerrin S.
A1 Stringham, Heather M.
A1 Trakalo, Joseph
A1 Banks, Eric
A1 Carey, Jason
A1 Carneiro, Mauricio O.
A1 DePristo, Mark
A1 Farjoun, Yossi
A1 Fennell, Timothy
A1 Goldstein, Jacqueline I.
A1 Grant, George
A1 Hrabé de Angelis, Martin
A1 Maguire, Jared
A1 Neale, Benjamin M.
A1 Poplin, Ryan
A1 Purcell, Shaun
A1 Schwarzmayr, Thomas
A1 Shakir, Khalid
A1 Smith, Joshua D.
A1 Strom, Tim M.
A1 Wieland, Thomas
A1 Lindstrom, Jaana
A1 Brandslund, Ivan
A1 Christensen, Cramer
A1 Surdulescu, Gabriela L.
A1 Lakka, Timo A.
A1 Doney, Alex S.F.
A1 Nilsson, Peter
A1 Wareham, Nicholas J.
A1 Langenberg, Claudia
A1 Varga, Tibor V.
A1 Franks, Paul W.
A1 Rolandsson, Olov
A1 Rosengren, Anders H.
A1 Farook, Vidya S.
A1 Thameem, Farook
A1 Puppala, Sobha
A1 Kumar, Satish
A1 Lehman, Donna M.
A1 Jenkinson, Christopher P.
A1 Curran, Joanne E.
A1 Hale, Daniel Esten
A1 Fowler, Sharon P.
A1 Arya, Rector
A1 DeFronzo, Ralph A.
A1 Abboud, Hanna E.
A1 Syvänen, Ann-Christine
A1 Hicks, Pamela J.
A1 Palmer, Nicholette D.
A1 Ng, Maggie C.Y.
A1 Bowden, Donald W.
A1 Freedman, Barry I.
A1 Esko, Tõnu
A1 Mägi, Reedik
A1 Milani, Lili
A1 Mihailov, Evelin
A1 Metspalu, Andres
A1 Narisu, Narisu
A1 Kinnunen, Leena
A1 Bonnycastle, Lori L.
A1 Swift, Amy
A1 Pasko, Dorota
A1 Wood, Andrew R.
A1 Fadista, João
A1 Pollin, Toni I.
A1 Barzilai, Nir
A1 Atzmon, Gil
A1 Glaser, Benjamin
A1 Thorand, Barbara
A1 Strauch, Konstantin
A1 Peters, Annette
A1 Roden, Michael
A1 Müller-Nurasyid, Martina
A1 Liang, Liming
A1 Kriebel, Jennifer
A1 Illig, Thomas
A1 Grallert, Harald
A1 Gieger, Christian
A1 Meisinger, Christa
A1 Lannfelt, Lars
A1 Musani, Solomon K.
A1 Griswold, Michael
A1 Taylor, Herman A.
A1 Wilson, Gregory
A1 Correa, Adolfo
A1 Oksa, Heikki
A1 Scott, William R.
A1 Afzal, Uzma
A1 Tan, Sian-Tsung
A1 Loh, Marie
A1 Chambers, John C.
A1 Sehmi, Jobanpreet
A1 Kooner, Jaspal Singh
A1 Lehne, Benjamin
A1 Cho, Yoon Shin
A1 Lee, Jong-Young
A1 Han, Bok-Ghee
A1 Käräjämäki, Annemari
A1 Qi, Qibin
A1 Qi, Lu
A1 Huang, Jinyan
A1 Hu, Frank B.
A1 Melander, Olle
A1 Orho-Melander, Marju
A1 Below, Jennifer E.
A1 Aguilar, David
A1 Wong, Tien Yin
A1 Liu, Jianjun
A1 Khor, Chiea-Chuen
A1 Chia, Kee Seng
A1 Lim, Wei Yen
A1 Cheng, Ching-Yu
A1 Chan, Edmund
A1 Tai, E Shyong
A1 Aung, Tin
A1 Linneberg, Allan
A1 Isomaa, Bo
A1 Meitinger, Thomas
A1 Tuomi, Tiinamaija
A1 Hakaste, Liisa
A1 Kravic, Jasmina
A1 Jørgensen, Marit E.
A1 Lauritzen, Torsten
A1 Deloukas, Panos
A1 Stirrups, Kathleen E.
A1 Owen, Katharine R.
A1 Farmer, Andrew J.
A1 Frayling, Timothy M.
A1 O'Rahilly, Stephen P.
A1 Walker, Mark
A1 Levy, Jonathan C.
A1 Hodgkiss, Dylan
A1 Hattersley, Andrew T.
A1 Kuulasmaa, Teemu
A1 Stančáková, Alena
A1 Barroso, Inês
A1 Bharadwaj, Dwaipayan
A1 Chan, Juliana
A1 Chandak, Giriraj R.
A1 Daly, Mark J.
A1 Donnelly, Peter J.
A1 Ebrahim, Shah B.
A1 Elliott, Paul
A1 Fingerlin, Tasha
A1 Froguel, Philippe
A1 Hu, Cheng
A1 Jia, Weiping
A1 Ma, Ronald C.W.
A1 McVean, Gilean
A1 Park, Taesung
A1 Prabhakaran, Dorairaj
A1 Sandhu, Manjinder
A1 Scott, James
A1 Sladek, Rob
A1 Tandon, Nikhil
A1 Teo, Yik Ying
A1 Zeggini, Eleftheria
A1 Watanabe, Richard M.
A1 Koistinen, Heikki A.
A1 Kesaniemi, Y. Antero
A1 Uusitupa, Matti
A1 Spector, Timothy D.
A1 Salomaa, Veikko
A1 Rauramaa, Rainer
A1 Palmer, Colin N.A.
A1 Prokopenko, Inga
A1 Morris, Andrew D.
A1 Bergman, Richard N.
A1 Collins, Francis S.
A1 Lind, Lars
A1 Ingelsson, Erik
A1 Tuomilehto, Jaakko
A1 Karpe, Fredrik
A1 Groop, Leif
A1 Jørgensen, Torben
A1 Hansen, Torben
A1 Pedersen, Oluf
A1 Kuusisto, Johanna
A1 Abecasis, Gonçalo
A1 Bell, Graeme I.
A1 Blangero, John
A1 Cox, Nancy J.
A1 Duggirala, Ravindranath
A1 Seielstad, Mark
A1 Wilson, James G.
A1 Dupuis, Josee
A1 Ripatti, Samuli
A1 Hanis, Craig L.
A1 Florez, Jose C.
A1 Mohlke, Karen L.
A1 Meigs, James B.
A1 Laakso, Markku
A1 Morris, Andrew P.
A1 Boehnke, Michael
A1 Altshuler, David
A1 McCarthy, Mark I.
A1 Gloyn, Anna L.
A1 Lindgren, Cecilia M.
YR 2017
UL http://diabetes.diabetesjournals.org/content/66/7/2019.abstract
AB To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.