| Literature DB >> 33402679 |
Vasiliki Lagou1,2,3, Reedik Mägi4, Jouke- Jan Hottenga5,6, Harald Grallert7,8, John R B Perry9, Nabila Bouatia-Naji10,11,12, Letizia Marullo13, Denis Rybin14, Rick Jansen15, Josine L Min16,17, Antigone S Dimas18, Anna Ulrich19, Liudmila Zudina19, Jesper R Gådin20, Longda Jiang19,21, Alessia Faggian19, Amélie Bonnefond10,11,19, Joao Fadista22, Maria G Stathopoulou23, Aaron Isaacs24,25,26, Sara M Willems24, Pau Navarro27, Toshiko Tanaka28, Anne U Jackson29, May E Montasser30, Jeff R O'Connell30, Lawrence F Bielak31, Rebecca J Webster32, Richa Saxena33,34,35,36, Jeanette M Stafford37, Beate St Pourcain16,17, Nicholas J Timpson16,17, Perttu Salo38, So-Youn Shin39, Najaf Amin40, Albert V Smith29,41,42, Guo Li43,44, Niek Verweij45, Anuj Goel1,46, Ian Ford47, Paul C D Johnson47,48, Toby Johnson49,50, Karen Kapur51, Gudmar Thorleifsson52, Rona J Strawbridge53,54,55, Laura J Rasmussen-Torvik56, Tõnu Esko4, Evelin Mihailov4, Tove Fall57, Ross M Fraser58,59, Anubha Mahajan1,60, Stavroula Kanoni49,61, Vilmantas Giedraitis62, Marcus E Kleber63, Günther Silbernagel64, Julia Meyer65, Martina Müller-Nurasyid65,66,67,68, Andrea Ganna69,70,71, Antti-Pekka Sarin72,73, Loic Yengo10,11,21, Dmitry Shungin74,75,76, Jian'an Luan9, Momoko Horikoshi1,77,78, Ping An79, Serena Sanna80,81, Yvonne Boettcher82,83, N William Rayner1,61,77, Ilja M Nolte84, Tatijana Zemunik85, Erik van Iperen86, Peter Kovacs83, Nicholas D Hastie27, Sarah H Wild58, Stela McLachlan58, Susan Campbell27, Ozren Polasek85, Olga Carlson87, Josephine Egan87, Wieland Kiess83,88, Gonneke Willemsen5, Johanna Kuusisto89, Markku Laakso89, Maria Dimitriou90, Andrew A Hicks91, Rainer Rauramaa92,93, Stefania Bandinelli94, Barbara Thorand8,95, Yongmei Liu96, Iva Miljkovic97, Lars Lind98, Alex Doney99, Markus Perola38,72,100, Aroon Hingorani101, Mika Kivimaki101, Meena Kumari101,102, Amanda J Bennett77, Christopher J Groves77, Christian Herder8,103,104, Heikki A Koistinen105,106,107, Leena Kinnunen105, Ulf de Faire108, Stephan J L Bakker109, Matti Uusitupa110, Colin N A Palmer99, J Wouter Jukema111,112, Naveed Sattar113, Anneli Pouta114,115, Harold Snieder84, Eric Boerwinkle116,117, James S Pankow118, Patrik K Magnusson119, Ulrika Krus120, Chiara Scapoli13, Eco J C N de Geus5,6, Matthias Blüher82,121, Bruce H R Wolffenbuttel122, Michael A Province79, Goncalo R Abecasis29, James B Meigs70,123,124, G Kees Hovingh125,126, Jaana Lindström127, James F Wilson27,58, Alan F Wright27, George V Dedoussis90, Stefan R Bornstein128, Peter E H Schwarz129,130,131, Anke Tönjes82,83, Bernhard R Winkelmann132, Bernhard O Boehm133, Winfried März63,134, Andres Metspalu4, Jackie F Price58, Panos Deloukas49,61,135, Antje Körner83,136, Timo A Lakka92,137, Sirkka M Keinanen-Kiukaanniemi138,139, Timo E Saaristo140,141, Richard N Bergman142, Jaakko Tuomilehto143,144,145,146, Nicholas J Wareham9, Claudia Langenberg9, Satu Männistö105, Paul W Franks75,147,148, Caroline Hayward27, Veronique Vitart27, Jaakko Kaprio72,144, Sophie Visvikis-Siest23, Beverley Balkau149,150, David Altshuler33,34,124, Igor Rudan58, Michael Stumvoll82,83, Harry Campbell58, Cornelia M van Duijn24,151, Christian Gieger7,8,95, Thomas Illig7,152,153, Luigi Ferrucci154, Nancy L Pedersen119, Peter P Pramstaller91,155,156, Michael Boehnke29, Timothy M Frayling157, Alan R Shuldiner30,158, Patricia A Peyser31, Sharon L R Kardia31, Lyle J Palmer159, Brenda W Penninx15, Pierre Meneton160, Tamara B Harris161, Gerjan Navis109, Pim van der Harst45,81, George Davey Smith162, Nita G Forouhi9, Ruth J F Loos9,163, Veikko Salomaa164, Nicole Soranzo39, Dorret I Boomsma5, Leif Groop72,120, Tiinamaija Tuomi72,120,165,166, Albert Hofman40,167,168, Patricia B Munroe49,50, Vilmundur Gudnason41,169, David S Siscovick43,44,170, Hugh Watkins1,46, Cecile Lecoeur10,11, Peter Vollenweider171, Anders Franco-Cereceda172, Per Eriksson20, Marjo-Riitta Jarvelin173,174, Kari Stefansson52,175, Anders Hamsten53,54,176, George Nicholson177, Fredrik Karpe77,178, Emmanouil T Dermitzakis179, Cecilia M Lindgren1,33,77,180, Mark I McCarthy1,77,178,60, Philippe Froguel10,11,19, Marika A Kaakinen19,181, Valeriya Lyssenko120,182, Richard M Watanabe121,183,184, Erik Ingelsson57,185,186, Jose C Florez34,136, Josée Dupuis187, Inês Barroso39,188,189, Andrew P Morris1,100,190,191, Inga Prokopenko192,193,194,195,196.
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.Entities:
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Year: 2021 PMID： 33402679 PMCID： PMC7785747 DOI： 10.1038/s41467-020-19366-9
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 17.694