Search

Your search keyword '"Richard M. Watanabe"' showing total 5 results
Start Over Author "Richard M. Watanabe" Journal nature genetics
5 results on '"Richard M. Watanabe"'

1. Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion

Author

Anne U. Jackson, Jeroen R. Huyghe, Jane Romm, Johanna Kuusisto, Laura J. Scott, Lingyao Yang, Kimberly F. Doheny, Gonçalo R. Abecasis, Tanya M. Teslovich, Hyun Min Kang, Francis S. Collins, Mark J. Daly, Richard M. Watanabe, Michael Boehnke, Benjamin M. Neale, Marie P. Fogarty, Elizabeth W. Pugh, Hua Ling, Heather M. Stringham, Peter S. Chines, Markku Laakso, Alena Stančáková, Henna Cederberg, Martin L. Buchkovich, Karen L. Mohlke, Christian Fuchsberger, Roxann G. Ingersoll, Xueling Sim, and Ivy McMullen

Subjects
Genetics, education.field_of_study, Insulin, medicine.medical_treatment, Population, Biology, medicine.disease, medicine, Metabolic syndrome, education, Exome, Allele frequency, Glycemic, Insulin processing, Proinsulin
Abstract

Karen Mohlke, Markku Laakso, Michael Boehnke and colleagues report the first application of the Illumina HumanExome Beadchip array, examining association with insulin and glycemic traits in 8,229 nondiabetic Finnish males from the population-based Metabolic Syndrome in Men (METSIM) study. They identify low-frequency coding variants at both known and newly associated loci with insulin processing and secretion.

Published
2012

2. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

Author

John R. B. Perry, James B. Meigs, José Dupuis, Luigi Ferrucci, Johan G. Eriksson, Vilmundur Gudnason, Eric J.G. Sijbrands, Jeanette S. Andrews, Jonna L. Grimsby, Lawrence F. Bielak, Peter Kovacs, Panos Deloukas, Marijana Peričić, Johannes H. Smit, Ruth J. F. Loos, Gonneke Willemsen, Eric Boerwinkle, Ben A. Oostra, Manuel Serrano-Ríos, Alena Stančáková, Meena Kumari, Antti Jula, Michael Marmot, Caroline S. Fox, Simon Heath, Guo Li, Ola Hansson, Gerard Waeber, Anne U. Jackson, Nicholas L. Smith, Markku Laakso, George Dedoussis, Aarno Palotie, Sara M. Willems, John F. Peden, Elisabeth Widen, Caroline Hayward, Alan F. Wright, Claes Ladenvall, May E. Montasser, María Teresa Martínez-Larrad, Peter Vollenweider, Louis Pérusse, Tamara B. Harris, Wen Hong L. Kao, Danijela Budimir, Denis Rybin, David B. Savage, Michael A. Province, Alisa K. Manning, Bruna Gigante, Najaf Amin, Lenore J. Launer, Naveed Sattar, Lori L. Bonnycastle, Göran Hallmans, Jeffrey R. O'Connell, Stéphane Lobbens, Jacques S. Beckmann, Gemma Cadby, J. Wouter Jukema, Maria Dimitriou, Michael Stumvoll, Max Vikström, Rona J. Strawbridge, Hugh Watkins, Lyle J. Palmer, Johanna Kuusisto, Aimo Ruokonen, Hanieh Yaghootkar, Yan V. Sun, Inês Barroso, Amy J. Swift, Nancy L. Pedersen, Lars Lind, Mladen Boban, Nita G. Forouhi, Ken K. Ong, Ivana Kolcic, Anke Tönjes, Timothy M. Frayling, Paul W. Franks, Narisu Narisu, Karin Leander, Serge Hercberg, Diana Zelenika, Sharon L.R. Kardia, Min A. Jhun, Marjo-Riitta Järvelin, Stella Trompet, Jaakko Kaprio, Toshiko Tanaka, David S. Siscovick, Toby Johnson, Cornelia M. van Duijn, Veikko Salomaa, Jose C. Florez, James F. Wilson, Leena Peltonen, Pilar Galan, Robert Clarke, Andrew A. Hicks, Claudia Langenberg, Anders Hamsten, David Couper, Albert Hofman, Dawn M. Waterworth, John Blangero, James S. Pankow, Nabila Bouatia-Naji, Sirkka Keinänen-Kiukaanniemi, Mark I. McCarthy, Valeriya Lyssenko, Leif Groop, Brenda W.J.H. Penninx, Ching-Ti Liu, Anuj Goel, Marina Pehlić, Michael Boehnke, Mika Kivimäki, Maria Sabater-Lleal, Emil Rehnberg, Ingrid B. Borecki, Ozren Polasek, Eco J. C. de Geus, Peter P. Pramstaller, Igor Rudan, Richard M. Watanabe, Pierre Meneton, Iva Miljkovic, Vincent Mooser, G. Mark Lathrop, John Beilby, Laura J. Rasmussen-Torvik, Arturo Corbató-Anchuelo, Yvonne Böttcher, Richard N. Bergman, Daniel R. Barnes, Paul C. D. Johnson, Mustafa Atalay, Aroon D. Hingorani, Olga D. Carlson, Perttu Salo, Jacqueline C.M. Witteman, Udo Seedorf, Timo Saaristo, Jian'an Luan, Nicholas J. Wareham, Gudny Eiriksdottir, Matti Uusitupa, Yongmei Liu, Jaakko Tuomilehto, Yurii S. Aulchenko, Peter Schwarz, Robert A. Scott, Lina Zgaga, Joseph Hung, Reedik Mägi, Maria Grazia Franzosi, Eric J. Brunner, Claude Bouchard, Ian Ford, Francis S. Collins, Ulf de Faire, Benjamin F. Voight, Erik Ingelsson, Mario A. Morken, Stefania Bandinelli, Nicole L. Glazer, Dmitry Shungin, Lars Lannfelt, André G. Uitterlinden, Tatijana Zemunik, Markus Perola, Kenneth Rice, Veronique Vitart, Kerrin S. Small, Jouke-Jan Hottenga, Han Chen, Jerome I. Rotter, Philippe Froguel, Karen L. Mohlke, Marie-Claude Vohl, Dorret I. Boomsma, Harry Campbell, Peter S. Chines, Pau Navarro, Vasiliki Lagou, Albert V. Smith, Kathleen Stirrups, Josephine M. Egan, Alan R. Shuldiner, Katri Räikkönen, Inga Prokopenko, Ping An, Rainer Rauramaa, Beverley Balkau, Thor Aspelund, Eleanor Wheeler, Mariza de Andrade, Richa Saxena, Jari Lahti, Cécile Lecoeur, Timo A. Lakka, Jennie Hui, Michael R. Erdos, Stavroula Kanoni, Kirsten Ohm Kyvik, Bengt Sennblad, Sarah H. Wild, Patricia A. Peyser, Patrik K. E. Magnusson, Claire Bellis, Elodie Eury, Jaana Lindström, Boston University [Boston] (BU), Broad Institute of Harvard and MIT, Partenaires INRAE, Massachusetts General Hospital, Massachusetts General Hospital [Boston], Department of Genetics [Boston], Harvard Medical School [Boston] (HMS), Department of Medicine, Université de Sherbrooke (UdeS), Addenbrooke's Hospital, Harvard Medical School [Boston] (HMS)-Beth Israel Deaconess Medical Center [Boston] (BIDMC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Université Lille Nord de France (COMUE), Department of Epidemiology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-Center for Social Epidemiology and Population Health, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford [Oxford], The Wellcome Trust Centre for Human Genetics [Oxford], The Netherlands Cancer Institute, Ontario Institute for Cancer Research, Mount Sinai Hospital [Toronto, Canada] (MSH), VU University Amsterdam, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Michigan System, Queen Mary University of London (QMUL), The Wellcome Trust Sanger Institute [Cambridge], Lund University [Lund], Diabetes Centre, Lund University, University of Helsinki, Wake Forest School of Medicine, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, University of Maryland School of Medicine, University of Maryland System, University of Edinburgh, University of Exeter, Department of Twin Research and Genetic Epidemiology, King's College London, London, Northwestern University [Evanston], National Institute of Health and Welfare, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Lund University Diabetes Centre, Umeå University, National Institutes of Health, Centre for Medical Systems Biology, Netherlands Genomics Initiative, Washington University in Saint Louis (WUSTL), Department of Health Sciences Research, Mayo Clinic, Wake Forest University, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland, Institute of Biomedicine, Physiology, University of Eastern Finland, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR S 1018, Université Paris-Sud - Paris 11 (UP11), Azienda Sanitaria Firenze, Department of Medical Genetics, Université de Lausanne (UNIL), Centre Hospitalier Universitaire Vaudois (CHUV), Queen Elizabeth II Medical Centre, Research Institute, University of Southern California (USC), University of Split, The University of Texas Health Science Center at Houston (UTHealth), Leipzig University, Pennington Biomedical Research Center, Department of Epidemiology & Public Health, University College of London [London] (UCL), San Carlos Clinical Hospital, University of North Carolina, Harokopio University, National Institute on Aging, Folkhälsan Research Centre, Vaasa Central Hospital, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychiatry, EMGO - Lifestyle, overweight and diabetes, Epidemiology, Immunology, Erasmus School of Social and Behavioural Sciences, Clinical Genetics, Ophthalmology, Internal Medicine, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium, Ahmadi, K.R., Ainali, C., Barrett, A., Bataille, V., Bell, J.T., Buil, A., Deloukas, P., Dermitzakis, E.T., Dimas, A.S., Durbin, R., Glass, D., Grundberg, E., Hassanali, N., Hedman, Å.K., Ingle, C., Knowles, D., Krestyaninova, M., Lindgren, C.M., Lowe, C.E., McCarthy, M.I., Meduri, E., di Meglio, P., Min, J.L., Montgomery, S.B., Nestle, F.O., Nica, A.C., Nisbet, J., O'Rahilly, S., Parts, L., Potter, S., Sekowska, M., Shin, S.Y., Small, K.S., Soranzo, N., Spector, T.D., Surdulescu, G., Travers, M.E., Tsaprouni, L., Tsoka, S., Wilk, A., Yang, T.P., Zondervan, K.T., Voight, B.F., Scott, L.J., Steinthorsdottir, V., Morris, A.P., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G., McCulloch, L.J., Ferreira, T., Grallert, H., Amin, N., Wu, G., Willer, C.J., Raychaudhuri, S., McCarroll, S.A., Langenberg, C., Hofmann, O.M., Dupuis, J., Qi, L., Segrè, A.V., van Hoek, M., Navarro, P., Ardlie, K., Balkau, B., Benediktsson, R., Bennett, A.J., Blagieva, R., Boerwinkle, E., Bonnycastle, L.L., Boström, K.B., Bravenboer, B., Bumpstead, S., Burtt, N.P., Charpentier, G., Chines, P.S., Cornelis, M., Couper, D.J., Crawford, G., Doney, A.S., Elliott, K.S., Elliott, A.L., Erdos, M.R., Fox, C.S., Franklin, C.S., Ganser, M., Gieger, C., Grarup, N., Green, T., Griffin, S., Groves, C.J., Guiducci, C., Hadjadj, S., Herder, C., Isomaa, B., Jackson, A.U., Johnson, P.R., Jørgensen, T., Kao, W.H., Klopp, N., Kong, A., Kraft, P., Kuusisto, J., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Marre, M., Meitinger, T., Midthjell, K., Morken, M.A., Narisu, N., Nilsson, P., Owen, K.R., Payne, F., Perry, J.R., Petersen, A.K., Platou, C., Proença, C., Prokopenko, I., Rathmann, W., Rayner, N.W., Robertson, N.R., Rocheleau, G., Roden, M., Sampson, M.J., Saxena, R., Shields, B.M., Shrader, P., Sigurdsson, G., Sparsø, T., Strassburger, K., Stringham, H.M., Sun, Q., Swift, A.J., Thorand, B., Tichet, J., Tuomi, T., van Dam, R.M., van Haeften, T.W., van Herpt, T., van Vliet-Ostaptchouk, J.V., Walters, G.B., Weedon, M.N., Wijmenga, C., Witteman, J., Bergman, R.N., Cauchi, S., Collins, F.S., Gloyn, A.L., Gyllensten, U., Hansen, T., Hide, W.A., Hitman, G.A., Hofman, A., Hunter, D.J., Hveem, K., Laakso, M., Mohlke, K.L., Morris, A.D., Palmer, C.N., Pramstaller, P.P., Rudan, I., Sijbrands, E., Stein, L.D., Tuomilehto, J., Uitterlinden, A., Walker, M., Wareham, N.J., Watanabe, R.M., Abecasis, G.R., Boehm, B.O., Campbell, H., Daly, M.J., Hattersley, A.T., Hu, F.B., Meigs, J.B., Pankow, J.S., Pedersen, O., Wichmann, H.E., Barroso, I., Florez, J.C., Frayling, T.M., Groop, L., Sladek, R., Thorsteinsdottir, U., Wilson, J.F., Illig, T., Froguel, P., van Duijn, C.M., Stefansson, K., Altshuler, D., Boehnke, M., Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA)

Subjects
Blood Glucose, Netherlands Twin Register (NTR), medicine.medical_treatment, [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Type 2 diabetes, SUSCEPTIBILITY, Body Mass Index, GLUCOSE, Blood Glucose/metabolism, Cholesterol, HDL/metabolism, Diabetes Mellitus, Type 2/genetics, Genome-Wide Association Study, Humans, Insulin/metabolism, Insulin Resistance/genetics, Polymorphism, Single Nucleotide, 0302 clinical medicine, Insulin, 2. Zero hunger, Genetics, 0303 health sciences, COMMON VARIANTS, 3. Good health, ENVIRONMENT INTERACTION, OBESITY, CORONARY-ARTERY-DISEASE, medicine.medical_specialty, 030209 endocrinology & metabolism, Accounting, Biology, Article, 03 medical and health sciences, Insulin resistance, SDG 3 - Good Health and Well-being, Internal medicine, Diabetes mellitus, medicine, 030304 developmental biology, Genetic association, Glycemic, loci, SNP, insulin, business.industry, Cholesterol, HDL, medicine.disease, Obesity, POLYMORPHISM, ASSOCIATION ANALYSIS, Endocrinology, Diabetes Mellitus, Type 2, TYPE-2 DIABETES RISK, Insulin Resistance, business
Abstract

Group Authors : DIAGRAM Consortium MUTHER Consortium variants influencing fasting glycemic traits and insulin resistance Seuls les 100 premiers auteurs ont été conservés dans la publication. La liste complète des auteurs et des des affiliations est disponible sur la publication https://www.nature.com/articles/ng.2274.pdf p. 667-669.; International audience; Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.

Published
2012

3. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Author

Kenneth Rice, Amy J. Swift, Veronique Vitart, Lu Qi, Kaisa Silander, Olivier Le Bacquer, Laura Crisponi, David S. Siscovick, Bo Isomaa, Anne U. Jackson, Anke Tönjes, Richard N. Bergman, Rosa Maria Roccasecca, Luigi Ferrucci, Narisu Narisu, Kari Stefansson, Holly E. Syddall, Giuseppe Paolisso, Kim L. Ward, Paul Elliott, Scott M. Grundy, Paul Johnson, Jerome I. Rotter, Philippe Froguel, James B. Meigs, George Davey Smith, Andrew T. Hattersley, Leena Peltonen, Eric J.G. Sijbrands, Serena Sanna, María TeresaMartínez-Larrad, David Altshuler, Harald Grallert, Caroline S. Fox, Nita G. Forouhi, Dorret I. Boomsma, Harry Campbell, Jean Tichet, Angelo Scuteri, Aroon D. Hingorani, Daniel S. Pearson, Meena Kumari, Silvia Naitza, Shah Ebrahim, Manjinder S. Sandhu, Jose C. Florez, Cyrus Cooper, David M. Nathan, Joseph Hung, Fredrik Karpe, Ozren Polasek, Philip J. Barter, Ruth McPherson, Benjamin F. Voight, Wolfgang Rathmann, Abbas Dehghan, Udo Seedorf, Beverley M. Shields, Antti Jula, Pau Navarro, Josephine M. Egan, Rune R. Frants, Leif Groop, Gunnar Sigursson, Seppo Koskinen, Vincent Mooser, François Pattou, Jing Hua Zhao, Irene Pichler, John F. Peden, Göran Hallmans, Toshiko Tanaka, Ruth J. F. Loos, Peter Kovacs, Andrew D. Morris, Cécile Lecoeur, Jeffrey R. O'Connell, Massimo Mangino, Nicole Vogelzangs, Rhian Gwilliam, Gordon H. Williams, Carina Zabena, Naomi Hammond, Amélie Bonnefond, Björn Zethelius, Joachim Spranger, Nancy L. Pedersen, Christopher J. Groves, Nicholas J. Timpson, George Dedoussis, Veikko Salomaa, Peter Henneman, Andrew Walley, Serge Hercberg, Ian N. M. Day, Simon Heath, Matt Neville, Alex S. F. Doney, Robert Clarke, Olov Rolandsson, Panos Deloukas, Eric Boerwinkle, Y. AnteroKesaniemi, Mike Sampson, Gerard Waeber, Sven Bergmann, Ben A. Oostra, Manuel Serrano-Ríos, Mandy van Hoek, Christine Cavalcanti-Proença, Anna L. Gloyn, Ulla Sovio, Andrew P. Morris, Anneli Pouta, Amanda J. Bennett, Paul Scheet, Peter Schwarz, Jaakko Tuomilehto, Hugh Watkins, Johanna Kuusisto, Denis Rybin, Anna LiisaHartikainen, Maria GraziaFranzosi, Unnur Thorsteinsdottir, Rafn Benediktsson, Alan F. Wright, Colin N. Apalmer, Anuj Goel, Yavuz Ariyurek, Lars Lind, Robert Sladek, Stefan R. Bornstein, Reedik Mägi, Laila Simpson, Tim D. Spector, Paul W. Franks, Nicholas L. Smith, John R. B. Perry, Peter Vollenweider, Suzannah Bumpstead, Ruth E. Pakyz, Christa Meisinger, Alan R. Shuldiner, Josée Dupuis, Man Li, Eric J. Brunner, Francis S. Collins, Torben Hansen, James F. Wilson, Guangju Zhai, Igor Rudan, Nicole L. Glazer, Marco Orrù, Pierre Meneton, Knut Borch-Johnsen, Eleanor Wheeler, Gonçalo R. Abecasis, Mark I. McCarthy, Jouke JanHottenga, Inga Prokopenko, Ping An, Jérôme Delplanque, Albert Hofman, Andrew B. Singleton, Gabe Crawford, Thomas A. Buchanan, Avan Aihie Sayer, Richard M. Watanabe, David Schlessinger, A C Fedson, André G. Uitterlinden, Frank B. Hu, Jaqueline C. MWitteman, Dhiraj Varma, Ingrid B. Borecki, Sutapa Mukherjee, Murielle Bochud, Barbara Thorand, Christian Gieger, Lori L. Bonnycastle, Stephen J. Sharp, Markus Perola, Caroline Hayward, Kristin Ardlie, J. Graessler, Robert W. Mahley, Toby Johnson, Jian'an Luan, Joshua C. Randall, Cornelia M. van Duijn, Samuli Ripatti, Ko Willems van Dijk, Valgerdur Steinthorsdottir, Yurii S. Aulchenko, G. Mark Lathrop, Christian Dina, Eleftheria Zeggini, Cecilia M. Lindgren, Stavroula Kanoni, Timothy M. Frayling, Dawn M. Waterworth, Marika Kaakinen, Timo T. Valle, Diana Zelenika, Yii Der IdaChen, Angela Silveira, Nigel W. Rayner, Aimo Ruokonen, Yun Li, Cristian Pattaro, Annelli Sandbæk, Richa Saxena, Danielle Posthuma, Steven A. McCarroll, Niels Grarup, Samy Hadjadj, Pilar Galan, Xijing Han, Lyle J. Palmer, Ulf Gyllensten, Peter P. Pramstaller, Manuela Uda, Jarred B. McAteer, Brenda W.J.H. Penninx, Debbie A Lawlor, Torben Jørgensen, Beatrice Knight, Yvonne Böttcher, Claudia Langenberg, Nicole Soranzo, Ghislain Rocheleau, Erik Ingelsson, Mario A. Morken, Michael Roden, Felicity Payne, David R. Hillman, Michael Marmot, Karen L. Mohlke, Heather M. Stringham, Bruce M. Psaty, Gudmar Thorleifsson, Yoav Ben-Shlomo, Inês Barroso, W. H. Linda Kao, James S. Pankow, Valeriya Lyssenko, Nicholas J. Wareham, Tiinamaija Tuomi, Ann ChristineSyvänen, Braxton D. Mitchell, Alisa K. Manning, Mika Kivimäki, Peter Wagner, Praveen Sethupathy, G. BragiWalters, Jaakko Kaprio, Kijoung Song, Marjo Riitta-Järvelin, Michael A. Province, Andrew A. Hicks, Marilyn C. Cornelis, Sarah H. Wild, David Meyre, Guillaume Charpentier, Patrik K. E. Magnusson, David Melzer, Jennie Hui, Peter Shrader, Michael Stumvoll, Mark O. Goodarzi, Michael R. Erdos, Oluf Pedersen, Andreas Pfeiffer, Augustine Kong, Christian Herder, Laura J. Scott, John W. GYarnell, Kirsten Ohm Kyvik, Beverley Balkau, Antje Fischer-Rosinsky, Gonneke Willemsen, Thomas Illig, Neelam Hassanali, Markku Laakso, Michael Boehnke, John Beilby, Christopher S. Franklin, Fernando Rivadeneira, M. Carola Zillikens, Michael N. Weedon, Antonio Cao, Mark E. Cooper, Simon C. Potter, Eco J. C. de Geus, H.-Erich Wichmann, Amanda F. Elliott, Lachlan J. McOin, Sophie Visvikis-Siest, Thomas Sparsø, Laura J. McCulloch, Taina K. Lajunen, Peter S. Chines, Nabila Bouatia-Naji, Medical Research Council (MRC), Biological Psychology, Functional Genomics, Neuroscience Campus Amsterdam - Anxiety & Depression, Neuroscience Campus Amsterdam - Attention & Cognition, EMGO+ - Mental Health, Ophthalmology, Epidemiology, Clinical Genetics, Dermatology, Internal Medicine, DIAGRAM Consortium, GIANT Consortium, Global BPgen Consortium, Anders Hamsten on behalf of Procardis Consortium, MAGIC investigators, Human genetics, Psychiatry, EMGO - Mental health, NCA - Attention & Cognition, and NCA - Anxiety & Depression

Subjects
Blood Glucose, Netherlands Twin Register (NTR), Candidate gene, Genome-wide association study, Type 2 diabetes, CIRCADIAN CLOCK, TRIGLYCERIDE LEVELS, 0302 clinical medicine, Delta-5 Fatty Acid Desaturase, Databases, Genetic, Homeostasis, GENETICS & HEREDITY, Anders Hamsten on behalf of Procardis Consortium, Child, Genetics, PLASMA-GLUCOSE, 0303 health sciences, Glucokinase regulatory protein, COMMON VARIANTS, 11 Medical And Health Sciences, Fasting, MAGIC investigators, 3. Good health, MODEL ASSESSMENT, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, ESSENTIAL COMPONENTS, Adolescent, DNA Copy Number Variations, Alleles, Blood Glucose/genetics, Blood Glucose/metabolism, DNA Copy Number Variations/genetics, Diabetes Mellitus, Type 2/genetics, Fasting/blood, Gene Expression Regulation, Genetic Loci/genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeostasis/genetics, Humans, Meta-Analysis as Topic, Polymorphism, Single Nucleotide/genetics, Quantitative Trait Loci/genetics, Quantitative Trait, Heritable, Reproducibility of Results, Quantitative Trait Loci, 030209 endocrinology & metabolism, Biology, DIAGRAM Consortium, INSULIN-SECRETION, Polymorphism, Single Nucleotide, Article, Fasting glucose, 03 medical and health sciences, Insulin resistance, SDG 3 - Good Health and Well-being, Diabetes mellitus, Internal medicine, genome wide association study, glucose, diabetes type 2, medicine, GIANT Consortium, Allele, GENOME-WIDE ASSOCIATION, Global BPgen Consortium, 030304 developmental biology, Glycemic, Science & Technology, genome-wide association beta-cell dysfunction plasma-glucose insulin-secretion triglyceride levels essential components model assessment common variants circadian clock disease risk, DISEASE RISK, 06 Biological Sciences, medicine.disease, Endocrinology, Diabetes Mellitus, Type 2, Genetic Loci, biology.protein, BETA-CELL DYSFUNCTION, Developmental Biology
Abstract

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46, 186 nondiabetic participants. Follow-up of 25 loci in up to 76, 558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

Published
2010
Full Text
View/download PDF

4. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion

Author

Michael Boehnke, Peter M. Nilsson, Marco Bugliani, Malin Fex, Johan G. Eriksson, Jaakko Tuomilehto, Nicolo Pulizzi, Richard M. Watanabe, Markku Laakso, Piero Marchetti, Peter Spégel, Cecilia Nagorny, Anna Jonsson, Valeriya Lyssenko, Bo Isomaa, Anne U. Jackson, Nils Wierup, Tiinamaija Tuomi, Hindrik Mulder, Richa Saxena, Frank Sundler, Michael R. Erdos, Leif Groop, Johanna Kuusisto, and David Altshuler

Subjects
Male, endocrine system, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Receptors, Melatonin, 030209 endocrinology & metabolism, Type 2 diabetes, Biology, Polymorphism, Single Nucleotide, Article, Cohort Studies, Melatonin, Islets of Langerhans, Mice, 03 medical and health sciences, Pineal gland, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Insulin Secretion, Genetics, medicine, Animals, Humans, Insulin, Genetic Predisposition to Disease, Aged, 030304 developmental biology, 0303 health sciences, Receptor, Melatonin, MT2, Middle Aged, medicine.disease, Rats, Insulin oscillation, Protein Transport, Endocrinology, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Gene Expression Regulation, Melatonin receptor 1B, Female, Hormone, medicine.drug
Abstract

Genome wide association studies revealed that variation in the Melatonin Receptor 1B gene (MTNR1B) is associated with insulin and glucose concentrations. Here we show that the risk genotype of this SNP predicts future type 2 diabetes (T2D) in two large prospective studies. Specifically, the risk genotype was associated with impairment of early insulin response to both oral and intravenous glucose and with faster deterioration of insulin secretion over time. We also show that the Melatonin Receptor 1B mRNA is expressed in human islets, and immunocytochemistry confirms that it is primarily localized in β-cells in islets. Non-diabetic individuals carrying the risk allele and patients with T2D showed increased expression of the receptor in islets. Insulin release from clonal β-cells in response to glucose was inhibited in the presence of melatonin. These data suggest that the circulating hormone melatonin, which is predominantly released from the pineal gland in the brain, is involved in the pathogenesis of T2D. Given the increased expression of Melatonin Receptor 1B in individuals at risk of T2D, the pathogenic effects are likely exerted via a direct inhibitory effect on β-cells. In view of these results, blocking the melatonin ligand-receptor system could be a therapeutic avenue in T2D.

Published
2009
Full Text
View/download PDF

5. Newly identified loci that influence lipid concentrations and risk of coronary artery disease

Author

Richard N. Bergman, Derrick A Bennett, Cristen J. Willer, Richard M. Watanabe, Nicholas J. Timpson, Karen L. Mohlke, Robert Clarke, Francis S. Collins, Laura J. Scott, Antonio Cao, Angelo Scuteri, Alan R. Shuldiner, Antonella Mulas, G. Mark Lathrop, Andrea Maschio, Samer S. Najjar, Diana Zelenika, Serena Sanna, William L. Duren, Michael Boehnke, Jaakko Tuomilehto, Pilar Galan, James B. Strait, Heather M. Stringham, Debbie A Lawlor, Rory Collins, Ramaiah Nagaraja, Anne U. Jackson, Yun Li, Jouko Sundvall, Sarah Parish, Manuela Uda, George Davey-Smith, Giuseppe Albai, Paul Scheet, Shah Ebrahim, Haiqing Shen, David Schlessinger, Pierre Meneton, Lori L. Bonnycastle, Simon Heath, Gonçalo R. Abecasis, Mario A. Morken, Wei-Min Chen, Edward G. Lakatta, Amy J. Swift, Yoav Ben-Shlomo, Narisu Narisu, Fabio Busonero, and Serge Hercberg

Subjects
medicine.medical_specialty, Apolipoprotein B, Coronary Artery Disease, 030204 cardiovascular system & hematology, Polymorphism, Single Nucleotide, Article, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Gene Frequency, Risk Factors, Internal medicine, Genetics, medicine, Humans, Computer Simulation, Allele frequency, Alleles, Triglycerides, 030304 developmental biology, Probability, 0303 health sciences, Likelihood Functions, biology, Cholesterol, Genome, Human, PCSK9, Haplotype, Cholesterol, HDL, Genetic Variation, Cholesterol, LDL, Lipids, Markov Chains, 3. Good health, Endocrinology, chemistry, Haplotypes, ABCA1, Case-Control Studies, LDL receptor, biology.protein, lipids (amino acids, peptides, and proteins), Lipoprotein
Abstract

To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls.

Published
2007

Catalog

Books, media, physical & digital resources
See catalog results