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

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; Meta-Analyses of Glucose and; Jaakko Tuomilehto

doi:10.1038/s41467-020-19366-9

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

Journal article

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

Vasiliki Lagou, Reedik Mägi, Jouke- Jan Hottenga, Harald Grallert, John Perry, Nabila Bouatia-Naji, Letizia Marullo, Denis Rybin, Rick Jansen, Josine Min, …

Nature communications, Vol.12(1), pp.24-24

2021

DOI: https://doi.org/10.1038/s41467-020-19366-9

PMID: 33402679

Abstract

Life Sciences

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 menand impaired glucose tolerance in women, however, the genetic component underlyingthis phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individualsof European descent without diabetes. Here we report sex dimorphism in allelic effects onfasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in wholeblood in women compared to men. We also observe sex-homogeneous effects on fastingglucose at seven novel loci. Fasting insulin in women shows stronger genetic correlationsthan in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio iscausally related to insulin resistance in women, but not in men. These results positiondissection of metabolic and glycemic health sex dimorphism as a steppingstone for under-standing differences in genetic effects between women and men in related phenotypes.

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Title: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
Creators - without role: Vasiliki Lagou - Wellcome Centre for Human Genetics
Reedik Mägi - Genomics
Jouke- Jan Hottenga - Vrije Universiteit Amsterdam
Harald Grallert - Helmholtz Zentrum München
John Perry - University of Cambridge
Nabila Bouatia-Naji - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Letizia Marullo - University of Ferrara
Denis Rybin - Boston University
Rick Jansen - VU University Medical Center [Amsterdam]
Josine Min - University of Bristol
Antigone Dimas - Biomedical Sciences Research Centre Alexander Fleming [Vari, Greece]
Anna Ulrich - Imperial College London
Liudmila Zudina - Imperial College London
Jesper Gådin - Karolinska Institutet
Longda Jiang - Imperial College London
Alessia Faggian - Imperial College London
Amélie Bonnefond - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Joao Fadista - Statens Serum Institut
Maria Stathopoulou - Gene
Aaron Isaacs - Erasmus MC
Sara Willems - Erasmus MC
Pau Navarro - MRC Institute of Genetics and Molecular Medicine
Toshiko Tanaka - National Institute on Aging
Anne Jackson - University of Michigan [Ann Arbor]
May Montasser - University of Maryland School of Medicine
Jeff O’connell - University of Maryland School of Medicine
Lawrence Bielak - University of Michigan [Ann Arbor]
Rebecca Webster - University of Western Australia
Richa Saxena - Broad Institute
Jeanette Stafford - Wake Forest University
Beate St Pourcain - University of Bristol
Nicholas Timpson - University of Bristol
Perttu Salo - National Institute for Health and Welfare [Helsinki]
So-Youn Shin - Wellcome Sanger Institute
Najaf Amin - Erasmus MC
Albert Smith - University of Michigan [Ann Arbor]
Guo Li - University of Washington
Niek Verweij - University of Groningen
Anuj Goel - Wellcome Centre for Human Genetics
Ian Ford - University of Glasgow
Paul Johnson - University of Glasgow
Toby Johnson - William Harvey Research Institute
Karen Kapur - University of Lausanne
Gudmar Thorleifsson - deCODE Genetics
Rona Strawbridge - Karolinska Institutet
Laura Rasmussen-Torvik - Northwestern University
Tõnu Esko - Genomics
Evelin Mihailov - Genomics
Tove Fall - Uppsala Universitet [Uppsala]
Ross Fraser - University of Edinburgh
Anubha Mahajan - Wellcome Centre for Human Genetics
Stavroula Kanoni - William Harvey Research Institute
Vilmantas Giedraitis - Uppsala Universitet [Uppsala]
Marcus Kleber - Faculty
Günther Silbernagel - Karl-Franzens-Universität Graz
Julia Meyer - Helmholtz Zentrum München
Martina Müller-Nurasyid - Helmholtz Zentrum München
Andrea Ganna - Massachusetts General Hospital
Antti-Pekka Sarin - Institute for Molecular Medicine Finland
Loic Yengo - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Dmitry Shungin - Umeå University
Jian’an Luan - University of Cambridge
Momoko Horikoshi - Wellcome Centre for Human Genetics
Ping An - Washington University School of Medicine in St. Louis
Serena Sanna - GeneTiCA
Yvonne Boettcher - Universität Leipzig [Leipzig]
N. William Rayner - Wellcome Centre for Human Genetics
Ilja Nolte - University Medical Center Groningen
Tatijana Zemunik - University of Split
Erik Van Iperen - Academic Medical Center
Peter Kovacs - Universität Leipzig [Leipzig]
Nicholas Hastie - MRC Institute of Genetics and Molecular Medicine
Sarah Wild - University of Edinburgh
Stela Mclachlan - University of Edinburgh
Susan Campbell - MRC Institute of Genetics and Molecular Medicine
Ozren Polasek - University of Split
Olga Carlson - National Institute on Aging
Josephine Egan - National Institute on Aging
Wieland Kiess - Universität Leipzig [Leipzig]
Gonneke Willemsen - Vrije Universiteit Amsterdam
Johanna Kuusisto - University of Eastern Finland
Markku Laakso - University of Eastern Finland
Maria Dimitriou - Harokopio University of Athens
Andrew Hicks - European Academy Bozen/Bolzano
Rainer Rauramaa - University of Kuopio
Stefania Bandinelli
Barbara Thorand - German Center for Diabetes Research
Yongmei Liu - Wake Forest University
Iva Miljkovic - University of Pittsburgh
Lars Lind - Uppsala Universitet [Uppsala]
Alex Doney - Ninewells Hospital
Markus Perola - National Institute for Health and Welfare [Helsinki]
Aroon Hingorani - University College London
Mika Kivimaki - University College London
Meena Kumari - University College London
Amanda Bennett - Oxford Centre for Diabetes, Endocrinology and Metabolism
Christopher Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism
Christian Herder - German Center for Diabetes Research
Heikki Koistinen - National Institute for Health and Welfare [Helsinki]
Leena Kinnunen - National Institute for Health and Welfare [Helsinki]
Meta-Analyses of Glucose and
Jaakko Tuomilehto - King Abdulaziz University
Publication Details: Nature communications, Vol.12(1), pp.24-24
Publisher: Nature Publishing Group
Identifiers: 9940531208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article