OBJECTIVE: To investigate the associations between obesity-predisposing genetic variants, cardiovascular biomarkers, and cardiovascular disease (CVD) risk in women with preexisting type 2 diabetes mellitus. METHODS AND RESULTS: We genotyped polymorphisms at nine established obesity loci in 1,395 women with diabetes from the Nurses' Health Study: 449 women developed CVD, and 946 women did not develop CVD. A genetic risk score (GRS) was derived by summing risk alleles for each individual. Four polymorphisms (rs9939609 [FTO], rs11084753 [KCTD15], rs10838738 [MTCH2], and rs10938397 [GNPDA2]) showed nominally significant associations with CVD. The GRS combining all obesity loci was linearly related to CVD risk (P = 0.013 for trend). The odds ratio was 1.08 per risk allele (95% confidence interval, 1.02-1.15; P = 0.01) after adjustment for body mass index and other conventional risk factors. Women with the highest quartile of GRS had 53% (95% confidence interval, 6%-122%) increased CVD risk, compared with those in the lowest quartile of GRS (P = 0.024). In addition, a higher GRS was associated with lower adiponectin levels (P = 0.02). Further adjustment for body mass index and other covariates did not change the association (P = 0.006). A higher GRS was also correlated with lower levels of high-density lipoprotein (P = 0.01). CONCLUSIONS: Obesity-predisposing variants may jointly affect CVD risk among women with diabetes.
OBJECTIVE: To investigate the associations between obesity-predisposing genetic variants, cardiovascular biomarkers, and cardiovascular disease (CVD) risk in women with preexisting type 2 diabetes mellitus. METHODS AND RESULTS: We genotyped polymorphisms at nine established obesity loci in 1,395 women with diabetes from the Nurses' Health Study: 449 women developed CVD, and 946 women did not develop CVD. A genetic risk score (GRS) was derived by summing risk alleles for each individual. Four polymorphisms (rs9939609 [FTO], rs11084753 [KCTD15], rs10838738 [MTCH2], and rs10938397 [GNPDA2]) showed nominally significant associations with CVD. The GRS combining all obesity loci was linearly related to CVD risk (P = 0.013 for trend). The odds ratio was 1.08 per risk allele (95% confidence interval, 1.02-1.15; P = 0.01) after adjustment for body mass index and other conventional risk factors. Women with the highest quartile of GRS had 53% (95% confidence interval, 6%-122%) increased CVD risk, compared with those in the lowest quartile of GRS (P = 0.024). In addition, a higher GRS was associated with lower adiponectin levels (P = 0.02). Further adjustment for body mass index and other covariates did not change the association (P = 0.006). A higher GRS was also correlated with lower levels of high-density lipoprotein (P = 0.01). CONCLUSIONS:Obesity-predisposing variants may jointly affect CVD risk among women with diabetes.
Authors: John C Chambers; Paul Elliott; Delilah Zabaneh; Weihua Zhang; Yun Li; Philippe Froguel; David Balding; James Scott; Jaspal S Kooner Journal: Nat Genet Date: 2008-05-04 Impact factor: 38.330
Authors: Timothy M Frayling; Nicholas J Timpson; Michael N Weedon; Eleftheria Zeggini; Rachel M Freathy; Cecilia M Lindgren; John R B Perry; Katherine S Elliott; Hana Lango; Nigel W Rayner; Beverley Shields; Lorna W Harries; Jeffrey C Barrett; Sian Ellard; Christopher J Groves; Bridget Knight; Ann-Marie Patch; Andrew R Ness; Shah Ebrahim; Debbie A Lawlor; Susan M Ring; Yoav Ben-Shlomo; Marjo-Riitta Jarvelin; Ulla Sovio; Amanda J Bennett; David Melzer; Luigi Ferrucci; Ruth J F Loos; Inês Barroso; Nicholas J Wareham; Fredrik Karpe; Katharine R Owen; Lon R Cardon; Mark Walker; Graham A Hitman; Colin N A Palmer; Alex S F Doney; Andrew D Morris; George Davey Smith; Andrew T Hattersley; Mark I McCarthy Journal: Science Date: 2007-04-12 Impact factor: 47.728
Authors: Ruth J F Loos; Cecilia M Lindgren; Shengxu Li; Eleanor Wheeler; Jing Hua Zhao; Inga Prokopenko; Michael Inouye; Rachel M Freathy; Antony P Attwood; Jacques S Beckmann; Sonja I Berndt; Kevin B Jacobs; Stephen J Chanock; Richard B Hayes; Sven Bergmann; Amanda J Bennett; Sheila A Bingham; Murielle Bochud; Morris Brown; Stéphane Cauchi; John M Connell; Cyrus Cooper; George Davey Smith; Ian Day; Christian Dina; Subhajyoti De; Emmanouil T Dermitzakis; Alex S F Doney; Katherine S Elliott; Paul Elliott; David M Evans; I Sadaf Farooqi; Philippe Froguel; Jilur Ghori; Christopher J Groves; Rhian Gwilliam; David Hadley; Alistair S Hall; Andrew T Hattersley; Johannes Hebebrand; Iris M Heid; Claudia Lamina; Christian Gieger; Thomas Illig; Thomas Meitinger; H-Erich Wichmann; Blanca Herrera; Anke Hinney; Sarah E Hunt; Marjo-Riitta Jarvelin; Toby Johnson; Jennifer D M Jolley; Fredrik Karpe; Andrew Keniry; Kay-Tee Khaw; Robert N Luben; Massimo Mangino; Jonathan Marchini; Wendy L McArdle; Ralph McGinnis; David Meyre; Patricia B Munroe; Andrew D Morris; Andrew R Ness; Matthew J Neville; Alexandra C Nica; Ken K Ong; Stephen O'Rahilly; Katharine R Owen; Colin N A Palmer; Konstantinos Papadakis; Simon Potter; Anneli Pouta; Lu Qi; Joshua C Randall; Nigel W Rayner; Susan M Ring; Manjinder S Sandhu; André Scherag; Matthew A Sims; Kijoung Song; Nicole Soranzo; Elizabeth K Speliotes; Holly E Syddall; Sarah A Teichmann; Nicholas J Timpson; Jonathan H Tobias; Manuela Uda; Carla I Ganz Vogel; Chris Wallace; Dawn M Waterworth; Michael N Weedon; Cristen J Willer; Xin Yuan; Eleftheria Zeggini; Joel N Hirschhorn; David P Strachan; Willem H Ouwehand; Mark J Caulfield; Nilesh J Samani; Timothy M Frayling; Peter Vollenweider; Gerard Waeber; Vincent Mooser; Panos Deloukas; Mark I McCarthy; Nicholas J Wareham; Inês Barroso; Kevin B Jacobs; Stephen J Chanock; Richard B Hayes; Claudia Lamina; Christian Gieger; Thomas Illig; Thomas Meitinger; H-Erich Wichmann; Peter Kraft; Susan E Hankinson; David J Hunter; Frank B Hu; Helen N Lyon; Benjamin F Voight; Martin Ridderstrale; Leif Groop; Paul Scheet; Serena Sanna; Goncalo R Abecasis; Giuseppe Albai; Ramaiah Nagaraja; David Schlessinger; Anne U Jackson; Jaakko Tuomilehto; Francis S Collins; Michael Boehnke; Karen L Mohlke Journal: Nat Genet Date: 2008-05-04 Impact factor: 38.330
Authors: Bonnie R Joubert; David M Reif; Stephen W Edwards; Kevin A Leiner; Edward E Hudgens; Peter Egeghy; Jane E Gallagher; Elaine Cohen Hubal Journal: BMC Med Genet Date: 2011-02-14 Impact factor: 2.103