A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
Manning, Alisa (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.,Harvard Medical School,Broad Institute
Highland, Heather M. (författare)
Univ Texas MD Anderson Canc Ctr, Human Genet Ctr, Houston, TX 77030 USA.;Univ Texas Hlth Sci Ctr Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA.;Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA.
Gasser, Jessica (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
Tukiainen, Taru (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.
Fontanillas, Pierre (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;23andMe, Mountain View, CA USA.
Grarup, Niels (författare)
Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
Ma, Clement (författare)
Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Wessel, Jennifer (författare)
Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN USA.;Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.
Chu, Audrey Y. (författare)
Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
Scott, Robert A. (författare)
Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
Goodarzi, Mark O. (författare)
Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.;Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA.
Blancher, Christine (författare)
Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England.
Buck, Gemma (författare)
Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England.
Buck, David (författare)
Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England.
Chines, Peter S. (författare)
NHGRI, NIH, Bethesda, MD 20892 USA.
Gabriel, Stacey (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Gjesing, Anette P. (författare)
Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
Trakalo, Joseph (författare)
Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, High Throughput Genom,Oxford Genom Ctr, Oxford, England.
Banks, Eric (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Carey, Jason (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Carneiro, Mauricio O. (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
DePristo, Mark (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Farjoun, Yossi (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Fennell, Timothy (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Goldstein, Jacqueline I. (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
Grant, George (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
de Angelis, Martin Hrabe (författare)
German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Expt Genet, Neuherberg, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Tech Univ Munich, Sch Life Sci Weihenstephan, Inst Expt Genet, Freising Weihenstephan, Germany.
Maguire, Jared (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Neale, Benjamin M. (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
Poplin, Ryan (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Purcell, Shaun (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Psychiat, New York, NY 10029 USA.
Schwarzmayr, Thomas (författare)
German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.
Shakir, Khalid (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
Smith, Joshua D. (författare)
Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA USA.
Strom, Tim M. (författare)
German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Tech Univ Munich, Inst Human Genet, Neuherberg, Germany.
Wieland, Thomas (författare)
German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany.
Lindstrom, Jaana (författare)
Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
Ninewells Hosp & Med Sch, Med Res Inst, Div Cardiovasc & Diabet Med, Dundee, Scotland.
Nilsson, Peter (författare)
Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups
Wareham, Nicholas J. (författare)
Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
Langenberg, Claudia (författare)
Univ Cambridge, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England.
Umeå universitet,Medicin,Department of Clinical Sciences, Lund University Diabetes Centre, and Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA,Lund Univ, Lund Univ Diabet Ctr, Dept Clin Sci, Malmo, Sweden.;Lund Univ, Genet & Mol Epidemiol Unit, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.
Strauch, Konstantin (författare)
German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Dept Genet Epidemiol, Munich, Germany.
Peters, Annette (författare)
German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Partner Site Munich Heart Alliance, Herz Kreislauf Forsch DZHK, Deutsch Zentrum, Munich, Germany.
Roden, Michael (författare)
Heinrich Heine Univ, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany.;Partner Dusseldorf, German Ctr Diabet Res, Dusseldorf, Germany.
Mueller-Nurasyid, Martina (författare)
German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Dept Genet Epidemiol, Munich, Germany.;Partner Site Munich Heart Alliance, Herz Kreislauf Forsch DZHK, Deutsch Zentrum, Munich, Germany.;Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
Liang, Liming (författare)
Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.
Kriebel, Jennifer (författare)
German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
Illig, Thomas (författare)
German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany.;Hannover Med Sch, Inst Human Genet, Hannover, Germany.
Grallert, Harald (författare)
German Ctr Diabet Res DZD, Neuherberg, Germany.;German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.;German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
Gieger, Christian (författare)
German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
Meisinger, Christa (författare)
German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.
Lannfelt, Lars(författare)
Musani, Solomon K. (författare)
Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA.
Griswold, Michael (författare)
Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA.
Taylor, Herman A., Jr. (författare)
Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
Wilson, Gregory, Sr. (författare)
Jackson State Univ, Coll Publ Serv, Jackson, MS USA.
Correa, Adolfo (författare)
Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
Lee, Jong-Young (författare)
Minist Hlth & Welf, Seoul, South Korea.
Han, Bok-Ghee (författare)
Korea Natl Res Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
Karajamaki, Annemari (författare)
Vaasa Hlth Care Ctr, Vaasa, Finland.;Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.
Qi, Qibin (författare)
Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
Qi, Lu (författare)
Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.
Huang, Jinyan (författare)
Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
Hu, Frank B. (författare)
Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
Melander, Olle (författare)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
Orho-Melander, Marju (författare)
Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
Below, Jennifer E. (författare)
Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA.
Aguilar, David (författare)
Baylor Coll Med, Cardiovasc Div, Houston, TX 77030 USA.
Wong, Tien Yin (författare)
Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.
Liu, Jianjun (författare)
Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore.
Khor, Chiea-Chuen (författare)
Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore.;ASTAR, Genome Inst Singapore, Div Human Genet, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore.
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Diabetiska komplikationer,Genomics, Diabetes and Endocrinology,Lund University Research Groups,Diabetic Complications
Jorgensen, Marit E. (författare)
Steno Diabet Ctr, Gentofte, Denmark.
Lauritzen, Torsten (författare)
Aarhus Univ, Dept Publ Hlth, Sect Gen Practice, Aarhus, Denmark.
Deloukas, Panos (författare)
Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
Stirrups, Kathleen E. (författare)
Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England.
Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.;Univ Cambridge, Inst Metab Sci, Med Res Labs, Cambridge, England.
Bharadwaj, Dwaipayan (författare)
CSIR Inst Genom & Integrat Biol, Funct Genom Unit, New Delhi, India.
Chan, Juliana (författare)
Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China.
Chandak, Giriraj R. (författare)
CSIR Ctr Cellular Mol Biol, Hyderabad, Andhra Pradesh, India.
Daly, Mark J. (författare)
Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Hong Kong, Peoples R China.
Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
Watanabe, Richard M. (författare)
Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA.;Univ Southern Calif, Keck Sch Med, Diabet & Obes Res Inst, Los Angeles, CA USA.
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
Jorgensen, Torben (författare)
Glostrup Univ Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark.
Hansen, Torben (författare)
Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
Pedersen, Oluf (författare)
Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA.
Florez, Jose C. (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.
Mohlke, Karen L. (författare)
Univ North Carolina Chapel Hill, Dept Genet, Chapel Hill, NC USA.
Meigs, James B. (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
Altshuler, David (författare)
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA.;MIT, Dept Biol, Cambridge, MA USA.
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England.,Broad Institute,Massachusetts General Hospital,University of Oxford
Lannfelt, L (författare)
Uppsala universitet,Geriatrik
Syvänen, Ann-Christine, 1950- (författare)
Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
V. Varga, Tibor (författare)
Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
Rosengren, Anders (författare)
Lund University,Lunds universitet,Diabetes - öpatofysiologi,Forskargrupper vid Lunds universitet,Diabetes - Islet Patophysiology,Lund University Research Groups
Franks, Paul (författare)
Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA;Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA. Harvard Medical School (creator_code:org_t)
et al
American Diabetes Association, 2017
2017
Engelska.
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
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.
Ämnesord
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)