BACKGROUND: Elevated insulin resistance (IR), triglycerides (TG), body mass index (BMI), and waist circumference (WC) are features of the metabolic syndrome. Although several single-nucleotide polymorphisms (SNPs) associated with these traits have been reported, no study has reported their risk allele frequencies and effect sizes among the major U.S. race/ethnic groups in a nationally representative sample. METHODS: We compared the risk allele frequencies of eight SNPs previously associated with IR, TG, BMI, or WC by race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American) in 3,030 participants of the National Health and Nutrition Examination Study III (NHANES III). In regression models predicting IR, TG, BMI, WC, and metabolic syndrome, we tested whether the SNP effect sizes on these traits varied by race/ethnicity. RESULTS: Risk allele frequencies varied by race/ethnicity for all eight loci (P<0.0001). The directionality of effects of the variants on IR, TG, WC, and BMI was generally consistent with previous observations and did not differ by race/ethnicity (P>0.001), although our study had low power for this test. No SNP predicted metabolic syndrome in any of the three groups (P>0.05). CONCLUSIONS: The significance of racial/ethnic differences in risk allele frequencies merits consideration if genetic discoveries are to have clinical and public health applicability.
BACKGROUND: Elevated insulin resistance (IR), triglycerides (TG), body mass index (BMI), and waist circumference (WC) are features of the metabolic syndrome. Although several single-nucleotide polymorphisms (SNPs) associated with these traits have been reported, no study has reported their risk allele frequencies and effect sizes among the major U.S. race/ethnic groups in a nationally representative sample. METHODS: We compared the risk allele frequencies of eight SNPs previously associated with IR, TG, BMI, or WC by race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American) in 3,030 participants of the National Health and Nutrition Examination Study III (NHANES III). In regression models predicting IR, TG, BMI, WC, and metabolic syndrome, we tested whether the SNP effect sizes on these traits varied by race/ethnicity. RESULTS: Risk allele frequencies varied by race/ethnicity for all eight loci (P<0.0001). The directionality of effects of the variants on IR, TG, WC, and BMI was generally consistent with previous observations and did not differ by race/ethnicity (P>0.001), although our study had low power for this test. No SNP predicted metabolic syndrome in any of the three groups (P>0.05). CONCLUSIONS: The significance of racial/ethnic differences in risk allele frequencies merits consideration if genetic discoveries are to have clinical and public health applicability.
Authors: Stacey B Gabriel; Stephen F Schaffner; Huy Nguyen; Jamie M Moore; Jessica Roy; Brendan Blumenstiel; John Higgins; Matthew DeFelice; Amy Lochner; Maura Faggart; Shau Neen Liu-Cordero; Charles Rotimi; Adebowale Adeyemo; Richard Cooper; Ryk Ward; Eric S Lander; Mark J Daly; David Altshuler Journal: Science Date: 2002-05-23 Impact factor: 47.728
Authors: Iris M Heid; Anne U Jackson; Joshua C Randall; Thomas W Winkler; Lu Qi; Valgerdur Steinthorsdottir; Gudmar Thorleifsson; M Carola Zillikens; Elizabeth K Speliotes; Reedik Mägi; Tsegaselassie Workalemahu; Charles C White; Nabila Bouatia-Naji; Tamara B Harris; Sonja I Berndt; Erik Ingelsson; Cristen J Willer; Michael N Weedon; Jian'an Luan; Sailaja Vedantam; Tõnu Esko; Tuomas O Kilpeläinen; Zoltán Kutalik; Shengxu Li; Keri L Monda; Anna L Dixon; Christopher C Holmes; Lee M Kaplan; Liming Liang; Josine L Min; Miriam F Moffatt; Cliona Molony; George Nicholson; Eric E Schadt; Krina T Zondervan; Mary F Feitosa; Teresa Ferreira; Hana Lango Allen; Robert J Weyant; Eleanor Wheeler; Andrew R Wood; Karol Estrada; Michael E Goddard; Guillaume Lettre; Massimo Mangino; Dale R Nyholt; Shaun Purcell; Albert Vernon Smith; Peter M Visscher; Jian Yang; Steven A McCarroll; James Nemesh; Benjamin F Voight; Devin Absher; Najaf Amin; Thor Aspelund; Lachlan Coin; Nicole L Glazer; Caroline Hayward; Nancy L Heard-Costa; Jouke-Jan Hottenga; Asa Johansson; Toby Johnson; Marika Kaakinen; Karen Kapur; Shamika Ketkar; Joshua W Knowles; Peter Kraft; Aldi T Kraja; Claudia Lamina; Michael F Leitzmann; Barbara McKnight; Andrew P Morris; Ken K Ong; John R B Perry; Marjolein J Peters; Ozren Polasek; Inga Prokopenko; Nigel W Rayner; Samuli Ripatti; Fernando Rivadeneira; Neil R Robertson; Serena Sanna; Ulla Sovio; Ida Surakka; Alexander Teumer; Sophie van Wingerden; Veronique Vitart; Jing Hua Zhao; Christine Cavalcanti-Proença; Peter S Chines; Eva Fisher; Jennifer R Kulzer; Cecile Lecoeur; Narisu Narisu; Camilla Sandholt; Laura J Scott; Kaisa Silander; Klaus Stark; Mari-Liis Tammesoo; Tanya M Teslovich; Nicholas John Timpson; Richard M Watanabe; Ryan Welch; Daniel I Chasman; Matthew N Cooper; John-Olov Jansson; Johannes Kettunen; Robert W Lawrence; Niina Pellikka; Markus Perola; Liesbeth Vandenput; Helene Alavere; Peter Almgren; Larry D Atwood; Amanda J Bennett; Reiner Biffar; Lori L Bonnycastle; Stefan R Bornstein; Thomas A Buchanan; Harry Campbell; Ian N M Day; Mariano Dei; Marcus Dörr; Paul Elliott; Michael R Erdos; Johan G Eriksson; Nelson B Freimer; Mao Fu; Stefan Gaget; Eco J C Geus; Anette P Gjesing; Harald Grallert; Jürgen Grässler; Christopher J Groves; Candace Guiducci; Anna-Liisa Hartikainen; Neelam Hassanali; Aki S Havulinna; Karl-Heinz Herzig; Andrew A Hicks; Jennie Hui; Wilmar Igl; Pekka Jousilahti; Antti Jula; Eero Kajantie; Leena Kinnunen; Ivana Kolcic; Seppo Koskinen; Peter Kovacs; Heyo K Kroemer; Vjekoslav Krzelj; Johanna Kuusisto; Kirsti Kvaloy; Jaana Laitinen; Olivier Lantieri; G Mark Lathrop; Marja-Liisa Lokki; Robert N Luben; Barbara Ludwig; Wendy L McArdle; Anne McCarthy; Mario A Morken; Mari Nelis; Matt J Neville; Guillaume Paré; Alex N Parker; John F Peden; Irene Pichler; Kirsi H Pietiläinen; Carl G P Platou; Anneli Pouta; Martin Ridderstråle; Nilesh J Samani; Jouko Saramies; Juha Sinisalo; Jan H Smit; Rona J Strawbridge; Heather M Stringham; Amy J Swift; Maris Teder-Laving; Brian Thomson; Gianluca Usala; Joyce B J van Meurs; Gert-Jan van Ommen; Vincent Vatin; Claudia B Volpato; Henri Wallaschofski; G Bragi Walters; Elisabeth Widen; Sarah H Wild; Gonneke Willemsen; Daniel R Witte; Lina Zgaga; Paavo Zitting; John P Beilby; Alan L James; Mika Kähönen; Terho Lehtimäki; Markku S Nieminen; Claes Ohlsson; Lyle J Palmer; Olli Raitakari; Paul M Ridker; Michael Stumvoll; Anke Tönjes; Jorma Viikari; Beverley Balkau; Yoav Ben-Shlomo; Richard N Bergman; Heiner Boeing; George Davey Smith; Shah Ebrahim; Philippe Froguel; Torben Hansen; Christian Hengstenberg; Kristian Hveem; Bo Isomaa; Torben Jørgensen; Fredrik Karpe; Kay-Tee Khaw; Markku Laakso; Debbie A Lawlor; Michel Marre; Thomas Meitinger; Andres Metspalu; Kristian Midthjell; Oluf Pedersen; Veikko Salomaa; Peter E H Schwarz; Tiinamaija Tuomi; Jaakko Tuomilehto; Timo T Valle; Nicholas J Wareham; Alice M Arnold; Jacques S Beckmann; Sven Bergmann; Eric Boerwinkle; Dorret I Boomsma; Mark J Caulfield; Francis S Collins; Gudny Eiriksdottir; Vilmundur Gudnason; Ulf Gyllensten; Anders Hamsten; Andrew T Hattersley; Albert Hofman; Frank B Hu; Thomas Illig; Carlos Iribarren; Marjo-Riitta Jarvelin; W H Linda Kao; Jaakko Kaprio; Lenore J Launer; Patricia B Munroe; Ben Oostra; Brenda W Penninx; Peter P Pramstaller; Bruce M Psaty; Thomas Quertermous; Aila Rissanen; Igor Rudan; Alan R Shuldiner; Nicole Soranzo; Timothy D Spector; Ann-Christine Syvanen; Manuela Uda; André Uitterlinden; Henry Völzke; Peter Vollenweider; James F Wilson; Jacqueline C Witteman; Alan F Wright; Gonçalo R Abecasis; Michael Boehnke; Ingrid B Borecki; Panos Deloukas; Timothy M Frayling; Leif C Groop; Talin Haritunians; David J Hunter; Robert C Kaplan; Kari E North; Jeffrey R O'Connell; Leena Peltonen; David Schlessinger; David P Strachan; Joel N Hirschhorn; Themistocles L Assimes; H-Erich Wichmann; Unnur Thorsteinsdottir; Cornelia M van Duijn; Kari Stefansson; L Adrienne Cupples; Ruth J F Loos; Inês Barroso; Mark I McCarthy; Caroline S Fox; 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Michael R Erdos; Johan G Eriksson; Maurizio F Facheris; Stephan B Felix; Pamela Fischer-Posovszky; Aaron R Folsom; Nele Friedrich; Nelson B Freimer; Mao Fu; Stefan Gaget; Pablo V Gejman; Eco J C Geus; Christian Gieger; Anette P Gjesing; Anuj Goel; Philippe Goyette; Harald Grallert; Jürgen Grässler; Danielle M Greenawalt; Christopher J Groves; Vilmundur Gudnason; Candace Guiducci; Anna-Liisa Hartikainen; Neelam Hassanali; Alistair S Hall; Aki S Havulinna; Caroline Hayward; Andrew C Heath; Christian Hengstenberg; Andrew A Hicks; Anke Hinney; Albert Hofman; Georg Homuth; Jennie Hui; Wilmar Igl; Carlos Iribarren; Bo Isomaa; Kevin B Jacobs; Ivonne Jarick; Elizabeth Jewell; Ulrich John; Torben Jørgensen; Pekka Jousilahti; Antti Jula; Marika Kaakinen; Eero Kajantie; Lee M Kaplan; Sekar Kathiresan; Johannes Kettunen; Leena Kinnunen; Joshua W Knowles; Ivana Kolcic; Inke R König; Seppo Koskinen; Peter Kovacs; Johanna Kuusisto; Peter Kraft; Kirsti Kvaløy; Jaana Laitinen; Olivier Lantieri; Chiara Lanzani; Lenore J Launer; Cecile Lecoeur; Terho Lehtimäki; Guillaume Lettre; Jianjun Liu; Marja-Liisa Lokki; Mattias Lorentzon; Robert N Luben; Barbara Ludwig; Paolo Manunta; Diana Marek; Michel Marre; Nicholas G Martin; Wendy L McArdle; Anne McCarthy; Barbara McKnight; Thomas Meitinger; Olle Melander; David Meyre; Kristian Midthjell; Grant W Montgomery; Mario A Morken; Andrew P Morris; Rosanda Mulic; Julius S Ngwa; Mari Nelis; Matt J Neville; Dale R Nyholt; Christopher J O'Donnell; Stephen O'Rahilly; Ken K Ong; Ben Oostra; Guillaume Paré; Alex N Parker; Markus Perola; Irene Pichler; Kirsi H Pietiläinen; Carl G P Platou; Ozren Polasek; Anneli Pouta; Suzanne Rafelt; Olli Raitakari; Nigel W Rayner; Martin Ridderstråle; Winfried Rief; Aimo Ruokonen; Neil R Robertson; Peter Rzehak; Veikko Salomaa; Alan R Sanders; Manjinder S Sandhu; Serena Sanna; Jouko Saramies; Markku J Savolainen; Susann Scherag; Sabine Schipf; Stefan Schreiber; Heribert Schunkert; Kaisa Silander; Juha Sinisalo; David S Siscovick; Jan H Smit; Nicole Soranzo; Ulla Sovio; Jonathan Stephens; Ida Surakka; Amy J Swift; Mari-Liis Tammesoo; Jean-Claude Tardif; Maris Teder-Laving; Tanya M Teslovich; John R Thompson; Brian Thomson; Anke Tönjes; Tiinamaija Tuomi; Joyce B J van Meurs; Gert-Jan van Ommen; Vincent Vatin; Jorma Viikari; Sophie Visvikis-Siest; Veronique Vitart; Carla I G Vogel; Benjamin F Voight; Lindsay L Waite; Henri Wallaschofski; G Bragi Walters; Elisabeth Widen; Susanna Wiegand; Sarah H Wild; Gonneke Willemsen; Daniel R Witte; Jacqueline C Witteman; Jianfeng Xu; Qunyuan Zhang; Lina Zgaga; Andreas Ziegler; Paavo Zitting; John P Beilby; I Sadaf Farooqi; Johannes Hebebrand; Heikki V Huikuri; Alan L James; Mika Kähönen; Douglas F Levinson; Fabio Macciardi; Markku S Nieminen; Claes Ohlsson; Lyle J Palmer; Paul M Ridker; Michael Stumvoll; Jacques S Beckmann; Heiner Boeing; Eric Boerwinkle; Dorret I Boomsma; Mark J Caulfield; Stephen J Chanock; Francis S Collins; L Adrienne Cupples; George Davey Smith; Jeanette Erdmann; Philippe Froguel; Henrik Grönberg; Ulf Gyllensten; Per Hall; Torben Hansen; Tamara B Harris; Andrew T Hattersley; Richard B Hayes; Joachim Heinrich; Frank B Hu; Kristian Hveem; Thomas Illig; Marjo-Riitta Jarvelin; Jaakko Kaprio; Fredrik Karpe; Kay-Tee Khaw; Lambertus A Kiemeney; Heiko Krude; Markku Laakso; Debbie A Lawlor; Andres Metspalu; Patricia B Munroe; Willem H Ouwehand; Oluf Pedersen; Brenda W Penninx; Annette Peters; Peter P Pramstaller; Thomas Quertermous; Thomas Reinehr; Aila Rissanen; Igor Rudan; Nilesh J Samani; Peter E H Schwarz; Alan R Shuldiner; Timothy D Spector; Jaakko Tuomilehto; Manuela Uda; André Uitterlinden; Timo T Valle; Martin Wabitsch; Gérard Waeber; Nicholas J Wareham; Hugh Watkins; James F Wilson; Alan F Wright; M Carola Zillikens; Nilanjan Chatterjee; Steven A McCarroll; Shaun Purcell; Eric E Schadt; Peter M Visscher; Themistocles L Assimes; Ingrid B Borecki; Panos Deloukas; Caroline S Fox; Leif C Groop; Talin Haritunians; David J Hunter; Robert C Kaplan; Karen L Mohlke; Jeffrey R O'Connell; Leena Peltonen; David Schlessinger; David P Strachan; Cornelia M van Duijn; H-Erich Wichmann; Timothy M Frayling; Unnur Thorsteinsdottir; Gonçalo R Abecasis; Inês Barroso; Michael Boehnke; Kari Stefansson; Kari E North; Mark I McCarthy; Joel N Hirschhorn; Erik Ingelsson; Ruth J F Loos Journal: Nat Genet Date: 2010-10-10 Impact factor: 38.330
Authors: Christopher Newton-Cheh; Toby Johnson; Vesela Gateva; Martin D Tobin; Murielle Bochud; Lachlan Coin; Samer S Najjar; Jing Hua Zhao; Simon C Heath; Susana Eyheramendy; Konstantinos Papadakis; Benjamin F Voight; Laura J Scott; Feng Zhang; Martin Farrall; Toshiko Tanaka; Chris Wallace; John C Chambers; Kay-Tee Khaw; Peter Nilsson; Pim van der Harst; Silvia Polidoro; Diederick E Grobbee; N Charlotte Onland-Moret; Michiel L Bots; Louise V Wain; Katherine S Elliott; Alexander Teumer; Jian'an Luan; Gavin Lucas; Johanna Kuusisto; Paul R Burton; David Hadley; Wendy L McArdle; Morris Brown; Anna Dominiczak; Stephen J Newhouse; Nilesh J Samani; John Webster; Eleftheria Zeggini; Jacques S Beckmann; Sven Bergmann; Noha Lim; Kijoung Song; Peter Vollenweider; Gerard Waeber; Dawn M Waterworth; Xin Yuan; Leif Groop; Marju Orho-Melander; Alessandra Allione; Alessandra Di Gregorio; Simonetta Guarrera; Salvatore Panico; Fulvio Ricceri; Valeria Romanazzi; Carlotta Sacerdote; Paolo Vineis; Inês Barroso; Manjinder S Sandhu; Robert N Luben; Gabriel J Crawford; Pekka Jousilahti; Markus Perola; Michael Boehnke; Lori L Bonnycastle; Francis S Collins; Anne U Jackson; Karen L Mohlke; Heather M Stringham; Timo T Valle; Cristen J Willer; Richard N Bergman; Mario A Morken; Angela Döring; Christian Gieger; Thomas Illig; Thomas Meitinger; Elin Org; Arne Pfeufer; H Erich Wichmann; Sekar Kathiresan; Jaume Marrugat; Christopher J O'Donnell; Stephen M Schwartz; David S Siscovick; Isaac Subirana; Nelson B Freimer; Anna-Liisa Hartikainen; Mark I McCarthy; Paul F O'Reilly; Leena Peltonen; Anneli Pouta; Paul E de Jong; Harold Snieder; Wiek H van Gilst; Robert Clarke; Anuj Goel; Anders Hamsten; John F Peden; Udo Seedorf; Ann-Christine Syvänen; Giovanni Tognoni; Edward G Lakatta; Serena Sanna; Paul Scheet; David Schlessinger; Angelo Scuteri; Marcus Dörr; Florian Ernst; Stephan B Felix; Georg Homuth; Roberto Lorbeer; Thorsten Reffelmann; Rainer Rettig; Uwe Völker; Pilar Galan; Ivo G Gut; Serge Hercberg; G Mark Lathrop; Diana Zelenika; Panos Deloukas; Nicole Soranzo; Frances M Williams; Guangju Zhai; Veikko Salomaa; Markku Laakso; Roberto Elosua; Nita G Forouhi; Henry Völzke; Cuno S Uiterwaal; Yvonne T van der Schouw; Mattijs E Numans; Giuseppe Matullo; Gerjan Navis; Göran Berglund; Sheila A Bingham; Jaspal S Kooner; John M Connell; Stefania Bandinelli; Luigi Ferrucci; Hugh Watkins; Tim D Spector; Jaakko Tuomilehto; David Altshuler; David P Strachan; Maris Laan; Pierre Meneton; Nicholas J Wareham; Manuela Uda; Marjo-Riitta Jarvelin; Vincent Mooser; Olle Melander; Ruth J F Loos; Paul Elliott; Gonçalo R Abecasis; Mark Caulfield; Patricia B Munroe Journal: Nat Genet Date: 2009-05-10 Impact factor: 38.330
Authors: Rene Baudrand; Mark O Goodarzi; Anand Vaidya; Patricia C Underwood; Jonathan S Williams; Xavier Jeunemaitre; Paul N Hopkins; Nancy Brown; Benjamin A Raby; Jessica Lasky-Su; Gail K Adler; Jinrui Cui; Xiuqing Guo; Kent D Taylor; Yii-Der I Chen; Anny Xiang; Leslie J Raffel; Thomas A Buchanan; Jerome I Rotter; Gordon H Williams; Luminita H Pojoga Journal: Metabolism Date: 2015-09-12 Impact factor: 8.694
Authors: Cécile M Povel; Jolanda M A Boer; N Charlotte Onland-Moret; Martijn E T Dollé; Edith J M Feskens; Yvonne T van der Schouw Journal: Cardiovasc Diabetol Date: 2012-10-29 Impact factor: 9.951