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- Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.
Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability.
Citation | “Sex-Dimorphic Genetic Effects And Novel Loci For Fasting Glucose And Insulin Variability.”. Nature Communications, p. 24. . |
Center | UCSD-UCLA |
Author | Vasiliki Lagou, Reedik Magi, Jouke- Jan Hottenga, Harald Grallert, John R B Perry, Nabila Bouatia-Naji, Letizia Marullo, Denis Rybin, Rick Jansen, Josine L Min, Antigone S Dimas, Anna Ulrich, Liudmila Zudina, Jesper R Gådin, Longda Jiang, Alessia Faggian, Amelie Bonnefond, João Fadista, Maria G Stathopoulou, Aaron Isaacs, Sara M Willems, Pau Navarro, Toshiko Tanaka, Anne U Jackson, May E Montasser, Jeff R O'Connell, Lawrence F Bielak, Rebecca J Webster, Richa Saxena, Jeanette M Stafford, Beate St Pourcain, Nicholas J Timpson, Perttu Salo, So-Youn Shin, Najaf Amin, Albert Smith V, Guo Li, Niek Verweij, Anuj Goel, Ian Ford, Paul C D Johnson, Toby Johnson, Karen Kapur, Gudmar Thorleifsson, Rona J Strawbridge, Laura J Rasmussen-Torvik, Tõnu Esko, Evelin Mihailov, Tove Fall, Ross M Fraser, Anubha Mahajan, Stavroula Kanoni, Vilmantas Giedraitis, Marcus E Kleber, Günther Silbernagel, Julia Meyer, Martina Müller-Nurasyid, Andrea Ganna, Antti-Pekka Sarin, Loic Yengo, Dmitry Shungin, Jian'an Luan, Momoko Horikoshi, Ping An, Serena Sanna, Yvonne Boettcher, William Rayner, Ilja M Nolte, Tatijana Zemunik, Erik van Iperen, Peter Kovacs, Nicholas D Hastie, Sarah H Wild, Stela McLachlan, Susan Campbell, Ozren Polasek, Olga Carlson, Josephine Egan, Wieland Kiess, Gonneke Willemsen, Johanna Kuusisto, Markku Laakso, Maria Dimitriou, Andrew A Hicks, Rainer Rauramaa, Stefania Bandinelli, Barbara Thorand, Yongmei Liu, Iva Miljkovic, Lars Lind, Alex Doney, Markus Perola, Aroon Hingorani, Mika Kivimaki, Meena Kumari, Amanda J Bennett, Christopher J Groves, Christian Herder, Heikki A Koistinen, Leena Kinnunen, Ulf de Faire, Stephan J L Bakker, Matti Uusitupa, Colin N A Palmer, Wouter Jukema, Naveed Sattar, Anneli Pouta, Harold Snieder, Eric Boerwinkle, James S Pankow, Patrik K Magnusson, Ulrika Krus, Chiara Scapoli, Eco J C N de Geus, Matthias Blüher, Bruce H R Wolffenbuttel, Michael A Province, Goncalo R Abecasis, James B Meigs, Kees Hovingh, Jaana Lindström, James F Wilson, Alan F Wright, George Dedoussis V, Stefan R Bornstein, Peter E H Schwarz, Anke Tönjes, Bernhard R Winkelmann, Bernhard O Boehm, Winfried März, Andres Metspalu, Jackie F Price, Panos Deloukas, Antje Körner, Timo A Lakka, Sirkka M Keinanen-Kiukaanniemi, Timo E Saaristo, Richard N Bergman, Jaakko Tuomilehto, Nicholas J Wareham, Claudia Langenberg, Satu Männistö, Paul W Franks, Caroline Hayward, Veronique Vitart, Jaakko Kaprio, Sophie Visvikis-Siest, Beverley Balkau, David Altshuler, Igor Rudan, Michael Stumvoll, Harry Campbell, Cornelia M van Duijn, Christian Gieger, Thomas Illig, Luigi Ferrucci, Nancy L Pedersen, Peter P Pramstaller, Michael Boehnke, Timothy M Frayling, Alan R Shuldiner, Patricia A Peyser, Sharon L R Kardia, Lyle J Palmer, Brenda W Penninx, Pierre Meneton, Tamara B Harris, Gerjan Navis, Pim van der Harst, George Davey Smith, Nita G Forouhi, Ruth J F Loos, Veikko Salomaa, Nicole Soranzo, Dorret I Boomsma, Leif Groop, Tiinamaija Tuomi, Albert Hofman, Patricia B Munroe, Vilmundur Gudnason, David S Siscovick, Hugh Watkins, Cecile Lecoeur, Peter Vollenweider, Anders Franco-Cereceda, Per Eriksson, Marjo-Riitta Järvelin, Kari Stefansson, Anders Hamsten, George Nicholson, Fredrik Karpe, Emmanouil T Dermitzakis, Cecilia M Lindgren, Mark I McCarthy, Philippe Froguel, Marika A Kaakinen, Valeriya Lyssenko, Richard M Watanabe, Erik Ingelsson, Jose C Florez, Josée Dupuis, Inês Barroso, Andrew P Morris, Inga Prokopenko, Meta-Analyses of Glucose and Insulin-related traits Consortium |
Abstract |
Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes. |
Year of Publication |
2021
|
Journal |
Nature communications
|
Volume |
12
|
Issue |
1
|
Number of Pages |
24
|
Date Published |
12/2021
|
ISSN Number |
2041-1723
|
DOI |
10.1038/s41467-020-19366-9
|
Alternate Journal |
Nat Commun
|
PMID |
33402679
|
PMCID |
PMC7785747
|
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