Literature DB >> 33407418

Genome-wide association study of circulating levels of glucagon during an oral glucose tolerance test.

Anna Jonsson1, Sara E Stinson2, Signe S Torekov2,3, Tine D Clausen4,5, Kristine Færch6, Louise Kelstrup7, Niels Grarup2, Elisabeth R Mathiesen5,7,8,9,10, Peter Damm5,7, Daniel R Witte10,11,12, Marit E Jørgensen6,13, Oluf Pedersen2, Jens Juul Holst2,3, Torben Hansen2.   

Abstract

BACKGROUND: In order to explore the pathophysiology underlying type 2 diabetes we examined the impact of gene variants associated with type 2 diabetes on circulating levels of glucagon during an oral glucose tolerance test (OGTT). Furthermore, we performed a genome-wide association study (GWAS) aiming to identify novel genomic loci affecting plasma glucagon levels.
METHODS: Plasma levels of glucagon were examined in samples obtained at three time points during an OGTT; 0, 30 and 120 min, in two separate cohorts with a total of up to 1899 individuals. Cross-sectional analyses were performed separately in the two cohorts and the results were combined in a meta-analysis.
RESULTS: A known type 2 diabetes variant in EYA2 was significantly associated with higher plasma glucagon level at 30 min during the OGTT (Beta 0.145, SE 0.038, P = 1.2 × 10-4) corresponding to a 7.4% increase in plasma glucagon level per effect allele. In the GWAS, we identified a marker in the MARCH1 locus, which was genome-wide significantly associated with reduced suppression of glucagon during the first 30 min of the OGTT (Beta - 0.210, SE 0.037, P = 1.9 × 10-8), equivalent to 8.2% less suppression per effect allele. Nine additional independent markers, not previously associated with type 2 diabetes, showed suggestive associations with reduced glucagon suppression during the first 30 min of the OGTT (P < 1.0 × 10-5).
CONCLUSIONS: A type 2 diabetes risk variant in the EYA2 locus was associated with higher plasma glucagon levels at 30 min. Ten additional variants were suggestively associated with reduced glucagon suppression without conferring increased type 2 diabetes risk.

Entities:  

Keywords:  GWAS; Glucagon; Type 2 diabetes

Mesh:

Substances:

Year:  2021        PMID: 33407418      PMCID: PMC7788944          DOI: 10.1186/s12920-020-00841-7

Source DB:  PubMed          Journal:  BMC Med Genomics        ISSN: 1755-8794            Impact factor:   3.063


  24 in total

1.  The human genome browser at UCSC.

Authors:  W James Kent; Charles W Sugnet; Terrence S Furey; Krishna M Roskin; Tom H Pringle; Alan M Zahler; David Haussler
Journal:  Genome Res       Date:  2002-06       Impact factor: 9.043

2.  Variance component model to account for sample structure in genome-wide association studies.

Authors:  Hyun Min Kang; Jae Hoon Sul; Susan K Service; Noah A Zaitlen; Sit-Yee Kong; Nelson B Freimer; Chiara Sabatti; Eleazar Eskin
Journal:  Nat Genet       Date:  2010-03-07       Impact factor: 38.330

3.  Glucagon and Amino Acids Are Linked in a Mutual Feedback Cycle: The Liver-α-Cell Axis.

Authors:  Jens J Holst; Nicolai J Wewer Albrechtsen; Jens Pedersen; Filip K Knop
Journal:  Diabetes       Date:  2017-02       Impact factor: 9.461

4.  Genetic determinants of circulating GIP and GLP-1 concentrations.

Authors:  Peter Almgren; Andreas Lindqvist; Ulrika Krus; Liisa Hakaste; Emilia Ottosson-Laakso; Olof Asplund; Emily Sonestedt; Rashmi B Prasad; Esa Laurila; Marju Orho-Melander; Olle Melander; Tiinamaija Tuomi; Jens Juul Holst; Peter M Nilsson; Nils Wierup; Leif Groop; Emma Ahlqvist
Journal:  JCI Insight       Date:  2017-11-02

5.  Next-generation genotype imputation service and methods.

Authors:  Sayantan Das; Lukas Forer; Sebastian Schönherr; Carlo Sidore; Adam E Locke; Alan Kwong; Scott I Vrieze; Emily Y Chew; Shawn Levy; Matt McGue; David Schlessinger; Dwight Stambolian; Po-Ru Loh; William G Iacono; Anand Swaroop; Laura J Scott; Francesco Cucca; Florian Kronenberg; Michael Boehnke; Gonçalo R Abecasis; Christian Fuchsberger
Journal:  Nat Genet       Date:  2016-08-29       Impact factor: 38.330

6.  Hyperglucagonaemia analysed by glucagon sandwich ELISA: nonspecific interference or truly elevated levels?

Authors:  Nicolai J Wewer Albrechtsen; Bolette Hartmann; Simon Veedfald; Johanne A Windeløv; Astrid Plamboeck; Kirstine N Bojsen-Møller; Thomas Idorn; Bo Feldt-Rasmussen; Filip K Knop; Tina Vilsbøll; Sten Madsbad; Carolyn F Deacon; Jens J Holst
Journal:  Diabetologia       Date:  2014-06-03       Impact factor: 10.122

7.  An atlas of genetic associations in UK Biobank.

Authors:  Oriol Canela-Xandri; Konrad Rawlik; Albert Tenesa
Journal:  Nat Genet       Date:  2018-10-22       Impact factor: 38.330

8.  New genetic loci link adipose and insulin biology to body fat distribution.

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Loïc Yengo; Weihua Zhang; Eva Albrecht; Johan Ärnlöv; Gillian M Arscott; Stefania Bandinelli; Amy Barrett; Claire Bellis; Amanda J Bennett; Christian Berne; Matthias Blüher; Stefan Böhringer; Fabrice Bonnet; Yvonne Böttcher; Marcel Bruinenberg; Delia B Carba; Ida H Caspersen; Robert Clarke; E Warwick Daw; Joris Deelen; Ewa Deelman; Graciela Delgado; Alex Sf Doney; Niina Eklund; Michael R Erdos; Karol Estrada; Elodie Eury; Nele Friedrich; Melissa E Garcia; Vilmantas Giedraitis; Bruna Gigante; Alan S Go; Alain Golay; Harald Grallert; Tanja B Grammer; Jürgen Gräßler; Jagvir Grewal; Christopher J Groves; Toomas Haller; Goran Hallmans; Catharina A Hartman; Maija Hassinen; Caroline Hayward; Kauko Heikkilä; Karl-Heinz Herzig; Quinta Helmer; Hans L Hillege; Oddgeir Holmen; Steven C Hunt; Aaron Isaacs; Till Ittermann; Alan L James; Ingegerd Johansson; Thorhildur Juliusdottir; Ioanna-Panagiota Kalafati; Leena Kinnunen; Wolfgang Koenig; Ishminder K Kooner; Wolfgang Kratzer; Claudia Lamina; Karin Leander; Nanette R Lee; Peter Lichtner; Lars Lind; Jaana Lindström; Stéphane Lobbens; Mattias Lorentzon; François Mach; Patrik Ke Magnusson; Anubha Mahajan; Wendy L McArdle; Cristina Menni; Sigrun Merger; Evelin Mihailov; Lili Milani; Rebecca Mills; Alireza Moayyeri; Keri L Monda; Simon P Mooijaart; Thomas W Mühleisen; Antonella Mulas; Gabriele Müller; Martina Müller-Nurasyid; Ramaiah Nagaraja; Michael A Nalls; Narisu Narisu; Nicola Glorioso; Ilja M Nolte; Matthias Olden; Nigel W Rayner; Frida Renstrom; Janina S Ried; Neil R Robertson; Lynda M Rose; Serena Sanna; Hubert Scharnagl; Salome Scholtens; Bengt Sennblad; Thomas Seufferlein; Colleen M Sitlani; Albert Vernon Smith; Kathleen Stirrups; Heather M Stringham; Johan Sundström; Morris A Swertz; Amy J Swift; Ann-Christine Syvänen; Bamidele O Tayo; Barbara Thorand; Gudmar Thorleifsson; Andreas Tomaschitz; Chiara Troffa; Floor Va van Oort; Niek Verweij; Judith M Vonk; Lindsay L Waite; Roman Wennauer; Tom Wilsgaard; Mary K Wojczynski; Andrew Wong; Qunyuan Zhang; Jing Hua Zhao; Eoin P Brennan; Murim Choi; Per Eriksson; Lasse Folkersen; Anders Franco-Cereceda; Ali G Gharavi; Åsa K Hedman; Marie-France Hivert; Jinyan Huang; Stavroula Kanoni; Fredrik Karpe; Sarah Keildson; Krzysztof Kiryluk; Liming Liang; Richard P Lifton; Baoshan Ma; Amy J McKnight; Ruth McPherson; Andres Metspalu; Josine L Min; Miriam F Moffatt; Grant W Montgomery; Joanne M Murabito; George Nicholson; Dale R Nyholt; Christian Olsson; John Rb Perry; Eva Reinmaa; Rany M Salem; Niina Sandholm; Eric E Schadt; Robert A Scott; Lisette Stolk; Edgar E Vallejo; Harm-Jan Westra; Krina T Zondervan; Philippe Amouyel; Dominique Arveiler; Stephan Jl Bakker; John Beilby; Richard N Bergman; John Blangero; Morris J Brown; Michel Burnier; Harry Campbell; Aravinda Chakravarti; Peter S Chines; Simone Claudi-Boehm; Francis S Collins; Dana C Crawford; John Danesh; Ulf de Faire; Eco Jc de Geus; Marcus Dörr; Raimund Erbel; Johan G Eriksson; Martin Farrall; Ele Ferrannini; Jean Ferrières; Nita G Forouhi; Terrence Forrester; Oscar H Franco; Ron T Gansevoort; Christian Gieger; Vilmundur Gudnason; Christopher A Haiman; Tamara B Harris; Andrew T Hattersley; Markku Heliövaara; Andrew A Hicks; Aroon D Hingorani; Wolfgang Hoffmann; Albert Hofman; Georg Homuth; Steve E Humphries; Elina Hyppönen; Thomas Illig; Marjo-Riitta Jarvelin; Berit Johansen; Pekka Jousilahti; Antti M Jula; Jaakko Kaprio; Frank Kee; Sirkka M Keinanen-Kiukaanniemi; Jaspal S Kooner; Charles Kooperberg; Peter Kovacs; Aldi T Kraja; Meena Kumari; Kari Kuulasmaa; Johanna Kuusisto; Timo A Lakka; Claudia Langenberg; Loic Le Marchand; Terho Lehtimäki; Valeriya Lyssenko; Satu Männistö; André Marette; Tara C Matise; Colin A McKenzie; Barbara McKnight; Arthur W Musk; Stefan Möhlenkamp; Andrew D Morris; Mari Nelis; Claes Ohlsson; Albertine J Oldehinkel; Ken K Ong; Lyle J Palmer; Brenda W Penninx; Annette Peters; Peter P Pramstaller; Olli T Raitakari; Tuomo Rankinen; D C Rao; Treva K Rice; Paul M Ridker; Marylyn D Ritchie; Igor Rudan; Veikko Salomaa; Nilesh J Samani; Jouko Saramies; Mark A Sarzynski; Peter Eh Schwarz; Alan R Shuldiner; Jan A Staessen; Valgerdur Steinthorsdottir; Ronald P Stolk; Konstantin Strauch; Anke Tönjes; Angelo Tremblay; Elena Tremoli; Marie-Claude Vohl; Uwe Völker; Peter Vollenweider; James F Wilson; Jacqueline C Witteman; Linda S Adair; Murielle Bochud; Bernhard O Boehm; Stefan R Bornstein; Claude Bouchard; Stéphane Cauchi; Mark J Caulfield; John C Chambers; Daniel I Chasman; Richard S Cooper; George Dedoussis; Luigi Ferrucci; Philippe Froguel; Hans-Jörgen Grabe; Anders Hamsten; Jennie Hui; Kristian Hveem; Karl-Heinz Jöckel; Mika Kivimaki; Diana Kuh; Markku Laakso; Yongmei Liu; Winfried März; Patricia B Munroe; Inger Njølstad; Ben A Oostra; Colin Na Palmer; Nancy L Pedersen; Markus Perola; Louis Pérusse; Ulrike Peters; Chris Power; Thomas Quertermous; Rainer Rauramaa; Fernando Rivadeneira; Timo E Saaristo; Danish Saleheen; Juha Sinisalo; P Eline Slagboom; Harold Snieder; Tim D Spector; Kari Stefansson; Michael Stumvoll; Jaakko Tuomilehto; André G Uitterlinden; Matti Uusitupa; Pim van der Harst; Giovanni Veronesi; Mark Walker; Nicholas J Wareham; Hugh Watkins; H-Erich Wichmann; Goncalo R Abecasis; Themistocles L Assimes; Sonja I Berndt; Michael Boehnke; Ingrid B Borecki; Panos Deloukas; Lude Franke; Timothy M Frayling; Leif C Groop; David J Hunter; Robert C Kaplan; Jeffrey R O'Connell; Lu Qi; David Schlessinger; David P Strachan; Unnur Thorsteinsdottir; Cornelia M van Duijn; Cristen J Willer; Peter M Visscher; Jian Yang; Joel N Hirschhorn; M Carola Zillikens; Mark I McCarthy; Elizabeth K Speliotes; Kari E North; Caroline S Fox; Inês Barroso; Paul W Franks; Erik Ingelsson; Iris M Heid; Ruth Jf Loos; L Adrienne Cupples; Andrew P Morris; Cecilia M Lindgren; Karen L Mohlke
Journal:  Nature       Date:  2015-02-12       Impact factor: 49.962

9.  A reference panel of 64,976 haplotypes for genotype imputation.

Authors:  Shane McCarthy; Sayantan Das; Warren Kretzschmar; Olivier Delaneau; Andrew R Wood; Alexander Teumer; Hyun Min Kang; Christian Fuchsberger; Petr Danecek; Kevin Sharp; Yang Luo; Carlo Sidore; Alan Kwong; Nicholas Timpson; Seppo Koskinen; Scott Vrieze; Laura J Scott; He Zhang; Anubha Mahajan; Jan Veldink; Ulrike Peters; Carlos Pato; Cornelia M van Duijn; Christopher E Gillies; Ilaria Gandin; Massimo Mezzavilla; Arthur Gilly; Massimiliano Cocca; Michela Traglia; Andrea Angius; Jeffrey C Barrett; Dorrett Boomsma; Kari Branham; Gerome Breen; Chad M Brummett; Fabio Busonero; Harry Campbell; Andrew Chan; Sai Chen; Emily Chew; Francis S Collins; Laura J Corbin; George Davey Smith; George Dedoussis; Marcus Dorr; Aliki-Eleni Farmaki; Luigi Ferrucci; Lukas Forer; Ross M Fraser; Stacey Gabriel; Shawn Levy; Leif Groop; Tabitha Harrison; Andrew Hattersley; Oddgeir L Holmen; Kristian Hveem; Matthias Kretzler; James C Lee; Matt McGue; Thomas Meitinger; David Melzer; Josine L Min; Karen L Mohlke; John B Vincent; Matthias Nauck; Deborah Nickerson; Aarno Palotie; Michele Pato; Nicola Pirastu; Melvin McInnis; J Brent Richards; Cinzia Sala; Veikko Salomaa; David Schlessinger; Sebastian Schoenherr; P Eline Slagboom; Kerrin Small; Timothy Spector; Dwight Stambolian; Marcus Tuke; Jaakko Tuomilehto; Leonard H Van den Berg; Wouter Van Rheenen; Uwe Volker; Cisca Wijmenga; Daniela Toniolo; Eleftheria Zeggini; Paolo Gasparini; Matthew G Sampson; James F Wilson; Timothy Frayling; Paul I W de Bakker; Morris A Swertz; Steven McCarroll; Charles Kooperberg; Annelot Dekker; David Altshuler; Cristen Willer; William Iacono; Samuli Ripatti; Nicole Soranzo; Klaudia Walter; Anand Swaroop; Francesco Cucca; Carl A Anderson; Richard M Myers; Michael Boehnke; Mark I McCarthy; Richard Durbin
Journal:  Nat Genet       Date:  2016-08-22       Impact factor: 38.330

10.  Discovery and refinement of loci associated with lipid levels.

Authors:  Cristen J Willer; Ellen M Schmidt; Sebanti Sengupta; Michael Boehnke; Panos Deloukas; Sekar Kathiresan; Karen L Mohlke; Erik Ingelsson; Gonçalo R Abecasis; Gina M Peloso; Stefan Gustafsson; Stavroula Kanoni; Andrea Ganna; Jin Chen; Martin L Buchkovich; Samia Mora; Jacques S Beckmann; Jennifer L Bragg-Gresham; Hsing-Yi Chang; Ayşe Demirkan; Heleen M Den Hertog; Ron Do; Louise A Donnelly; Georg B Ehret; Tõnu Esko; Mary F Feitosa; Teresa Ferreira; Krista Fischer; Pierre Fontanillas; Ross M Fraser; Daniel F Freitag; Deepti Gurdasani; Kauko Heikkilä; Elina Hyppönen; Aaron Isaacs; Anne U Jackson; Åsa Johansson; Toby Johnson; Marika Kaakinen; Johannes Kettunen; Marcus E Kleber; Xiaohui Li; Jian'an Luan; Leo-Pekka Lyytikäinen; Patrik K E Magnusson; Massimo Mangino; Evelin Mihailov; May E Montasser; Martina Müller-Nurasyid; Ilja M Nolte; Jeffrey R O'Connell; Cameron D Palmer; Markus Perola; Ann-Kristin Petersen; Serena Sanna; Richa Saxena; Susan K Service; Sonia Shah; Dmitry Shungin; Carlo Sidore; Ci Song; Rona J Strawbridge; Ida Surakka; Toshiko Tanaka; Tanya M Teslovich; Gudmar Thorleifsson; Evita G Van den Herik; Benjamin F Voight; Kelly A Volcik; Lindsay L Waite; Andrew Wong; Ying Wu; Weihua Zhang; Devin Absher; Gershim Asiki; Inês Barroso; Latonya F Been; Jennifer L Bolton; Lori L Bonnycastle; Paolo Brambilla; Mary S Burnett; Giancarlo Cesana; Maria Dimitriou; Alex S F Doney; Angela Döring; Paul Elliott; Stephen E Epstein; Gudmundur Ingi Eyjolfsson; Bruna Gigante; Mark O Goodarzi; Harald Grallert; Martha L Gravito; Christopher J Groves; Göran Hallmans; Anna-Liisa Hartikainen; Caroline Hayward; Dena Hernandez; Andrew A Hicks; Hilma Holm; Yi-Jen Hung; Thomas Illig; Michelle R Jones; Pontiano Kaleebu; John J P Kastelein; Kay-Tee Khaw; Eric Kim; Norman Klopp; Pirjo Komulainen; Meena Kumari; Claudia Langenberg; Terho Lehtimäki; Shih-Yi Lin; Jaana Lindström; Ruth J F Loos; François Mach; Wendy L McArdle; Christa Meisinger; Braxton D Mitchell; Gabrielle Müller; Ramaiah Nagaraja; Narisu Narisu; Tuomo V M Nieminen; Rebecca N Nsubuga; Isleifur Olafsson; Ken K Ong; Aarno Palotie; Theodore Papamarkou; Cristina Pomilla; Anneli Pouta; Daniel J Rader; Muredach P Reilly; Paul M Ridker; Fernando Rivadeneira; Igor Rudan; Aimo Ruokonen; Nilesh Samani; Hubert Scharnagl; Janet Seeley; Kaisa Silander; Alena Stančáková; Kathleen Stirrups; Amy J Swift; Laurence Tiret; Andre G Uitterlinden; L Joost van Pelt; Sailaja Vedantam; Nicholas Wainwright; Cisca Wijmenga; Sarah H Wild; Gonneke Willemsen; Tom Wilsgaard; James F Wilson; Elizabeth H Young; Jing Hua Zhao; Linda S Adair; Dominique Arveiler; Themistocles L Assimes; Stefania Bandinelli; Franklyn Bennett; Murielle Bochud; Bernhard O Boehm; Dorret I Boomsma; Ingrid B Borecki; Stefan R Bornstein; Pascal Bovet; Michel Burnier; Harry Campbell; Aravinda Chakravarti; John C Chambers; Yii-Der Ida Chen; Francis S Collins; Richard S Cooper; John Danesh; George Dedoussis; Ulf de Faire; Alan B Feranil; Jean Ferrières; Luigi Ferrucci; Nelson B Freimer; Christian Gieger; Leif C Groop; Vilmundur Gudnason; Ulf Gyllensten; Anders Hamsten; Tamara B Harris; Aroon Hingorani; Joel N Hirschhorn; Albert Hofman; G Kees Hovingh; Chao Agnes Hsiung; Steve E Humphries; Steven C Hunt; Kristian Hveem; Carlos Iribarren; Marjo-Riitta Järvelin; Antti Jula; Mika Kähönen; Jaakko Kaprio; Antero Kesäniemi; Mika Kivimaki; Jaspal S Kooner; Peter J Koudstaal; Ronald M Krauss; Diana Kuh; Johanna Kuusisto; Kirsten O Kyvik; Markku Laakso; Timo A Lakka; Lars Lind; Cecilia M Lindgren; Nicholas G Martin; Winfried März; Mark I McCarthy; Colin A McKenzie; Pierre Meneton; Andres Metspalu; Leena Moilanen; Andrew D Morris; Patricia B Munroe; Inger Njølstad; Nancy L Pedersen; Chris Power; Peter P Pramstaller; Jackie F Price; Bruce M Psaty; Thomas Quertermous; Rainer Rauramaa; Danish Saleheen; Veikko Salomaa; Dharambir K Sanghera; Jouko Saramies; Peter E H Schwarz; Wayne H-H Sheu; Alan R Shuldiner; Agneta Siegbahn; Tim D Spector; Kari Stefansson; David P Strachan; Bamidele O Tayo; Elena Tremoli; Jaakko Tuomilehto; Matti Uusitupa; Cornelia M van Duijn; Peter Vollenweider; Lars Wallentin; Nicholas J Wareham; John B Whitfield; Bruce H R Wolffenbuttel; Jose M Ordovas; Eric Boerwinkle; Colin N A Palmer; Unnur Thorsteinsdottir; Daniel I Chasman; Jerome I Rotter; Paul W Franks; Samuli Ripatti; L Adrienne Cupples; Manjinder S Sandhu; Stephen S Rich
Journal:  Nat Genet       Date:  2013-10-06       Impact factor: 38.330

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  1 in total

1.  Hyperglucagonemia in Pediatric Adiposity Associates With Cardiometabolic Risk Factors but Not Hyperglycemia.

Authors:  Sara E Stinson; Anna E Jonsson; Ierai Fernández de Retana Alzola; Morten A V Lund; Christine Frithioff-Bøjsøe; Louise Aas Holm; Cilius E Fonvig; Oluf Pedersen; Lars Ängquist; Thorkild I A Sørensen; Jens J Holst; Michael Christiansen; Jens-Christian Holm; Bolette Hartmann; Torben Hansen
Journal:  J Clin Endocrinol Metab       Date:  2022-05-17       Impact factor: 6.134

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