OBJECTIVE: Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. METHODS: We combined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0 x 10(-4) for each the men- and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. RESULTS: The ADIPOQ locus showed genome-wide significant p-values in the combined (p=4.3 x 10(-24)) as well as in both women- and men-specific analyses (p=8.7 x 10(-17) and p=2.5 x 10(-11), respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci exhibited association with plasma adiponectin (p>0.01). CONCLUSIONS: We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which explains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci explained the sex differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
OBJECTIVE: Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. METHODS: We combined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p-values less than 1.0 x 10(-4) for each the men- and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. RESULTS: The ADIPOQ locus showed genome-wide significant p-values in the combined (p=4.3 x 10(-24)) as well as in both women- and men-specific analyses (p=8.7 x 10(-17) and p=2.5 x 10(-11), respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci exhibited association with plasma adiponectin (p>0.01). CONCLUSIONS: We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which explains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci explained the sex differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.
Entities:
Keywords:
adiponectin; cardiovascular disease; genome-wide association study; metabolic syndrome; polymorphism
Authors: Abbas Dehghan; Anna Köttgen; Qiong Yang; Shih-Jen Hwang; Wh Linda Kao; Fernando Rivadeneira; Eric Boerwinkle; Daniel Levy; Albert Hofman; Brad C Astor; Emelia J Benjamin; Cornelia M van Duijn; Jacqueline C Witteman; Josef Coresh; Caroline S Fox Journal: Lancet Date: 2008-10-01 Impact factor: 79.321
Authors: Veronique Vitart; Igor Rudan; Caroline Hayward; Nicola K Gray; James Floyd; Colin N A Palmer; Sara A Knott; Ivana Kolcic; Ozren Polasek; Juergen Graessler; James F Wilson; Anthony Marinaki; Philip L Riches; Xinhua Shu; Branka Janicijevic; Nina Smolej-Narancic; Barbara Gorgoni; Joanne Morgan; Susan Campbell; Zrinka Biloglav; Lovorka Barac-Lauc; Marijana Pericic; Irena Martinovic Klaric; Lina Zgaga; Tatjana Skaric-Juric; Sarah H Wild; William A Richardson; Peter Hohenstein; Charley H Kimber; Albert Tenesa; Louise A Donnelly; Lynette D Fairbanks; Martin Aringer; Paul M McKeigue; Stuart H Ralston; Andrew D Morris; Pavao Rudan; Nicholas D Hastie; Harry Campbell; Alan F Wright Journal: Nat Genet Date: 2008-03-09 Impact factor: 38.330
Authors: Hua Ling; Dawn M Waterworth; Heide A Stirnadel; Toni I Pollin; Philip J Barter; Y Antero Kesäniemi; Robert W Mahley; Ruth McPherson; Gérard Waeber; Thomas P Bersot; Jonathan C Cohen; Scott M Grundy; Vincent E Mooser; Braxton D Mitchell Journal: Obesity (Silver Spring) Date: 2009-01-22 Impact factor: 5.002
Authors: Helmut Laumen; Akuma D Saningong; Iris M Heid; Jochen Hess; Christian Herder; Melina Claussnitzer; Jens Baumert; Claudia Lamina; Wolfgang Rathmann; Eva-Maria Sedlmeier; Norman Klopp; Barbara Thorand; H-Erich Wichmann; Thomas Illig; Hans Hauner Journal: Diabetes Date: 2008-12-15 Impact factor: 9.461
Authors: Sagiv Shifman; Martina Johannesson; Michal Bronstein; Sam X Chen; David A Collier; Nicholas J Craddock; Kenneth S Kendler; Tao Li; Michael O'Donovan; F Anthony O'Neill; Michael J Owen; Dermot Walsh; Daniel R Weinberger; Cuie Sun; Jonathan Flint; Ariel Darvasi Journal: PLoS Genet Date: 2008-02 Impact factor: 5.917
Authors: Marie-France Hivert; Alisa K Manning; Jarred B McAteer; Jose C Florez; Josée Dupuis; Caroline S Fox; Christopher J O'Donnell; L Adrienne Cupples; James B Meigs Journal: Diabetes Date: 2008-09-05 Impact factor: 9.461
Authors: Yurii S Aulchenko; Samuli Ripatti; Ida Lindqvist; Dorret Boomsma; Iris M Heid; Peter P Pramstaller; Brenda W J H Penninx; A Cecile J W Janssens; James F Wilson; Tim Spector; Nicholas G Martin; Nancy L Pedersen; Kirsten Ohm Kyvik; Jaakko Kaprio; Albert Hofman; Nelson B Freimer; Marjo-Riitta Jarvelin; Ulf Gyllensten; Harry Campbell; Igor Rudan; Asa Johansson; Fabio Marroni; Caroline Hayward; Veronique Vitart; Inger Jonasson; Cristian Pattaro; Alan Wright; Nick Hastie; Irene Pichler; Andrew A Hicks; Mario Falchi; Gonneke Willemsen; Jouke-Jan Hottenga; Eco J C de Geus; Grant W Montgomery; John Whitfield; Patrik Magnusson; Juha Saharinen; Markus Perola; Kaisa Silander; Aaron Isaacs; Eric J G Sijbrands; Andre G Uitterlinden; Jacqueline C M Witteman; Ben A Oostra; Paul Elliott; Aimo Ruokonen; Chiara Sabatti; Christian Gieger; Thomas Meitinger; Florian Kronenberg; Angela Döring; H-Erich Wichmann; Johannes H Smit; Mark I McCarthy; Cornelia M van Duijn; Leena Peltonen Journal: Nat Genet Date: 2008-12-07 Impact factor: 38.330
Authors: Cristen J Willer; Elizabeth K Speliotes; Ruth J F Loos; Shengxu Li; Cecilia M Lindgren; Iris M Heid; Sonja I Berndt; Amanda L Elliott; Anne U Jackson; Claudia Lamina; Guillaume Lettre; Noha Lim; Helen N Lyon; Steven A McCarroll; Konstantinos Papadakis; Lu Qi; Joshua C Randall; Rosa Maria Roccasecca; Serena Sanna; Paul Scheet; Michael N Weedon; Eleanor Wheeler; Jing Hua Zhao; Leonie C Jacobs; Inga Prokopenko; Nicole Soranzo; Toshiko Tanaka; Nicholas J Timpson; Peter Almgren; Amanda Bennett; Richard N Bergman; Sheila A Bingham; Lori L Bonnycastle; Morris Brown; Noël P Burtt; Peter Chines; Lachlan Coin; Francis S Collins; John M Connell; Cyrus Cooper; George Davey Smith; Elaine M Dennison; Parimal Deodhar; Paul Elliott; Michael R Erdos; Karol Estrada; David M Evans; Lauren Gianniny; Christian Gieger; Christopher J Gillson; Candace Guiducci; Rachel Hackett; David Hadley; Alistair S Hall; Aki S Havulinna; Johannes Hebebrand; Albert Hofman; Bo Isomaa; Kevin B Jacobs; Toby Johnson; Pekka Jousilahti; Zorica Jovanovic; Kay-Tee Khaw; Peter Kraft; Mikko Kuokkanen; Johanna Kuusisto; Jaana Laitinen; Edward G Lakatta; Jian'an Luan; Robert N Luben; Massimo Mangino; Wendy L McArdle; Thomas Meitinger; Antonella Mulas; Patricia B Munroe; Narisu Narisu; Andrew R Ness; Kate Northstone; Stephen O'Rahilly; Carolin Purmann; Matthew G Rees; Martin Ridderstråle; Susan M Ring; Fernando Rivadeneira; Aimo Ruokonen; Manjinder S Sandhu; Jouko Saramies; Laura J Scott; Angelo Scuteri; Kaisa Silander; Matthew A Sims; Kijoung Song; Jonathan Stephens; Suzanne Stevens; Heather M Stringham; Y C Loraine Tung; Timo T Valle; Cornelia M Van Duijn; Karani S Vimaleswaran; Peter Vollenweider; Gerard Waeber; Chris Wallace; Richard M Watanabe; Dawn M Waterworth; Nicholas Watkins; Jacqueline C M Witteman; Eleftheria Zeggini; Guangju Zhai; M Carola Zillikens; David Altshuler; Mark J Caulfield; Stephen J Chanock; I Sadaf Farooqi; Luigi Ferrucci; Jack M Guralnik; Andrew T Hattersley; Frank B Hu; Marjo-Riitta Jarvelin; Markku Laakso; Vincent Mooser; Ken K Ong; Willem H Ouwehand; Veikko Salomaa; Nilesh J Samani; Timothy D Spector; Tiinamaija Tuomi; Jaakko Tuomilehto; Manuela Uda; André G Uitterlinden; Nicholas J Wareham; Panagiotis Deloukas; Timothy M Frayling; Leif C Groop; Richard B Hayes; David J Hunter; Karen L Mohlke; Leena Peltonen; David Schlessinger; David P Strachan; H-Erich Wichmann; Mark I McCarthy; Michael Boehnke; Inês Barroso; Gonçalo R Abecasis; Joel N Hirschhorn Journal: Nat Genet Date: 2008-12-14 Impact factor: 38.330
Authors: L Y Han; Q H Wu; M L Jiao; Y H Hao; L B Liang; L J Gao; D G Legge; H Quan; M M Zhao; N Ning; Z Kang; H Sun Journal: Diabetologia Date: 2011-06-03 Impact factor: 10.122
Authors: Sarah S Cohen; Marilie D Gammon; Kari E North; Robert C Millikan; Ethan M Lange; Scott M Williams; Wei Zheng; Qiuyin Cai; Jirong Long; Jeffrey R Smith; Lisa B Signorello; William J Blot; Charles E Matthews Journal: Obesity (Silver Spring) Date: 2011-01-27 Impact factor: 5.002
Authors: Ying Wu; Yun Li; Ethan M Lange; Damien C Croteau-Chonka; Christopher W Kuzawa; Thomas W McDade; Li Qin; Ghenadie Curocichin; Judith B Borja; Leslie A Lange; Linda S Adair; Karen L Mohlke Journal: Hum Mol Genet Date: 2010-09-27 Impact factor: 6.150
Authors: Damien C Croteau-Chonka; Ying Wu; Yun Li; Marie P Fogarty; Leslie A Lange; Christopher W Kuzawa; Thomas W McDade; Judith B Borja; Jingchun Luo; Omar AbdelBaky; Terry P Combs; Linda S Adair; Ethan M Lange; Karen L Mohlke Journal: Hum Mol Genet Date: 2011-10-18 Impact factor: 6.150
Authors: C Menzaghi; S De Cosmo; M Copetti; L Salvemini; C De Bonis; D Mangiacotti; G Fini; F Pellegrini; V Trischitta Journal: Diabetologia Date: 2011-01-13 Impact factor: 10.122
Authors: S Sandy An; Nicholette D Palmer; Anthony J G Hanley; Julie T Ziegler; W Mark Brown; Steven M Haffner; Jill M Norris; Jerome I Rotter; Xiuqing Guo; Y-D Ida Chen; Lynne E Wagenknecht; Carl D Langefeld; Donald W Bowden Journal: Genet Epidemiol Date: 2012-10-02 Impact factor: 2.135
Authors: L Maria Belalcazar; George D Papandonatos; Jeanne M McCaffery; Inga Peter; Nicholas M Pajewski; Bahar Erar; Nicholette D Allred; Ashok Balasubramanyam; Donald W Bowden; Ariel Brautbar; F Xavier Pi-Sunyer; Christie M Ballantyne; Gordon S Huggins Journal: Physiol Genomics Date: 2015-03-10 Impact factor: 3.107