Publication: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Publié dans:

Auteurs: Vasiliki Lagou, Reedik Mägi, Jouke- Jan Hottenga, Harald Grallert, John Perry, Nabila Bouatia-Naji, Letizia Marullo, Denis Rybin, Rick Jansen, Josine Min, Antigone Dimas, Anna Ulrich, Liudmila Zudina, Jesper Gådin, Longda Jiang, Alessia Faggian, Amélie Bonnefond, Joao Fadista, Maria Stathopoulou, Aaron Isaacs, Sara Willems, Pau Navarro, Toshiko Tanaka, Anne Jackson, May Montasser, Jeff O’connell, Lawrence Bielak, Rebecca Webster, Richa Saxena, Jeanette Stafford, Beate St Pourcain, Nicholas Timpson, Perttu Salo, So-Youn Shin, Najaf Amin, Albert Smith, Guo Li, Niek Verweij, Anuj Goel, Ian Ford, Paul Johnson, Toby Johnson, Karen Kapur, Gudmar Thorleifsson, Rona Strawbridge, Laura Rasmussen-Torvik, Tõnu Esko, Evelin Mihailov, Tove Fall, Ross Fraser, Anubha Mahajan, Stavroula Kanoni, Vilmantas Giedraitis, Marcus 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, N. William Rayner, Ilja Nolte, Tatijana Zemunik, Erik Van Iperen, Peter Kovacs, Nicholas Hastie, Sarah Wild, Stela Mclachlan, Susan Campbell, Ozren Polasek, Olga Carlson, Josephine Egan, Wieland Kiess, Gonneke Willemsen, Johanna Kuusisto, Markku Laakso, Maria Dimitriou, Andrew Hicks, Rainer Rauramaa, Stefania Bandinelli, Barbara Thorand, Yongmei Liu, Iva Miljkovic, Lars Lind, Alex Doney, Markus Perola, Aroon Hingorani, Mika Kivimaki, Meena Kumari, Amanda Bennett, Christopher Groves, Christian Herder, Heikki Koistinen, Leena Kinnunen, Ulf De Faire, Stephan Bakker, Matti Uusitupa, Colin Palmer, J. Wouter Jukema, Naveed Sattar, Anneli Pouta, Harold Snieder, Eric Boerwinkle, James Pankow, Patrik Magnusson, Ulrika Krus, Chiara Scapoli, Eco de Geus, Matthias Blüher, Bruce Wolffenbuttel, Michael Province, Goncalo Abecasis, James Meigs, G. Kees Hovingh, Jaana Lindström, James Wilson, Alan Wright, George Dedoussis, Stefan Bornstein, Peter Schwarz, Anke Tönjes, Bernhard Winkelmann, Bernhard Boehm, Winfried März, Andres Metspalu, Jackie Price, Panos Deloukas, Antje Körner, Timo Lakka, Sirkka Keinanen-Kiukaanniemi, Timo Saaristo, Richard Bergman, Jaakko Tuomilehto, Nicholas Wareham, Claudia Langenberg, Satu Männistö, Paul Franks, Caroline Hayward, Veronique Vitart, Jaakko Kaprio, Sophie Visvikis-Siest, Beverley Balkau, David Altshuler, Igor Rudan, Michael Stumvoll, Harry Campbell, Cornelia van Duijn, Christian Gieger, Thomas Illig, Luigi Ferrucci, Nancy Pedersen, Peter Pramstaller, Michael Boehnke, Timothy Frayling, Alan Shuldiner, Patricia Peyser, Sharon Kardia, Lyle Palmer, Brenda Penninx, Pierre Meneton, Tamara Harris, Gerjan Navis, Pim van Der Harst, George Davey Smith, Nita Forouhi, Ruth Loos, Veikko Salomaa, Nicole Soranzo, Dorret Boomsma, Leif Groop, Tiinamaija Tuomi, Albert Hofman, Patricia Munroe, Vilmundur Gudnason, David Siscovick, Hugh Watkins, Cecile Lecoeur, Peter Vollenweider, Anders Franco-Cereceda, Per Eriksson, Marjo-Riitta Jarvelin, Kari Stefansson, Anders Hamsten, George Nicholson, Fredrik Karpe, Emmanouil Dermitzakis, Cecilia Lindgren, Mark Mccarthy, Philippe Froguel, Marika Kaakinen, Valeriya Lyssenko, Richard Watanabe, Erik Ingelsson, Jose Florez, Josée Dupuis, Inês Barroso, Andrew Morris, Inga Prokopenko

Résumé

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 under- standing differences in genetic effects between women and men in related phenotypes.

Lien vers Pubmed [PMID] – 33402679

Lien vers HAL – univ-lorraine-03684745

Lien vers le DOI – 10.1038/s41467-020-19366-9