Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: The EpiDREAM genetic study
Sonia S. Anand,Sonia S. Anand,David Meyre,David Meyre,Guillaume Paré,Guillaume Paré,Swneke D. Bailey,Changchun Xie,Xiaohe Zhang,Xiaohe Zhang,Alexandre Montpetit,Dipika Desai,Jackie Bosch,Jackie Bosch,Viswanathan Mohan,Rafael Diaz,Matthew J. McQueen,Matthew J. McQueen,Heather J. Cordell,Bernard Keavney,Salim Yusuf,Salim Yusuf,Daniel Gaudet,Hertzel C. Gerstein,Hertzel C. Gerstein,James C. Engert +25 more
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TLDR
T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.Abstract:
OBJECTIVE To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population. RESEARCH DESIGN AND METHODS In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up. RESULTS Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052). CONCLUSIONS T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.read more
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Diabetes and Associated Complications in the South Asian Population
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References
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TL;DR: This article conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent, and identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association.
Journal ArticleDOI
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis
Benjamin F. Voight,Benjamin F. Voight,Laura J. Scott,Valgerdur Steinthorsdottir,Andrew P. Morris,Christian Dina,Christian Dina,Ryan P. Welch,Eleftheria Zeggini,Eleftheria Zeggini,Cornelia Huth,Yurii S. Aulchenko,Gudmar Thorleifsson,Laura J. McCulloch,Teresa Ferreira,Harald Grallert,Najaf Amin,Guanming Wu,Cristen J. Willer,Soumya Raychaudhuri,Soumya Raychaudhuri,Soumya Raychaudhuri,Steve McCarroll,Steve McCarroll,Claudia Langenberg,Oliver Hofmann,Josée Dupuis,Lu Qi,Lu Qi,Ayellet V. Segrè,Ayellet V. Segrè,Mandy van Hoek,Pau Navarro,Kristin Ardlie,Beverley Balkau,Rafn Benediktsson,Amanda J. Bennett,Roza Blagieva,Eric Boerwinkle,Lori L. Bonnycastle,Kristina Bengtsson Boström,Bert Bravenboer,Suzannah Bumpstead,N P Burtt,Guillaume Charpentier,Peter S. Chines,Marilyn C. Cornelis,David Couper,Gabe Crawford,Alex S. F. Doney,Katherine S. Elliott,Amanda F. Elliott,Amanda F. Elliott,Michael R. Erdos,Caroline S. Fox,Christopher S. Franklin,Martha Ganser,Christian Gieger,Niels Grarup,Todd Green,Todd Green,Simon J. Griffin,Christopher J. Groves,Candace Guiducci,Samy Hadjadj,Neelam Hassanali,Christian Herder,Bo Isomaa,Anne U. Jackson,Paul Johnson,Torben Jørgensen,Torben Jørgensen,Wen H. L. Kao,Norman Klopp,Augustine Kong,Peter Kraft,Johanna Kuusisto,Torsten Lauritzen,Man Li,Aloysius G Lieverse,Cecilia M. Lindgren,Valeriya Lyssenko,Michel Marre,Michel Marre,Thomas Meitinger,Kristian Midthjell,Mario A. Morken,Narisu Narisu,Peter M. Nilsson,Katharine R. Owen,Felicity Payne,John R. B. Perry,Ann-Kristin Petersen,Carl G. P. Platou,Christine Proença,Inga Prokopenko,Inga Prokopenko,Wolfgang Rathmann,N. William Rayner,N. William Rayner,Neil R. Robertson,Neil R. Robertson,Ghislain Rocheleau,Michael Roden,Mike Sampson,Richa Saxena,Richa Saxena,Beverley M. Shields,Peter Shrader,Gunnar Sigurdsson,Thomas Sparsø,Klaus Strassburger,Heather M. Stringham,Qi Sun,Amy J. Swift,Barbara Thorand,Jean Tichet,Tiinamaija Tuomi,Rob M. van Dam,Timon W. van Haeften,Thijs T. W. van Herpt,Jana V. van Vliet-Ostaptchouk,G. Bragi Walters,Michael N. Weedon,Cisca Wijmenga,Jacqueline C. M. Witteman,Richard N. Bergman,Stéphane Cauchi,Francis S. Collins,Anna L. Gloyn,Ulf Gyllensten,Torben Hansen,Winston Hide,Graham A. Hitman,Albert Hofman,David J. Hunter,Kristian Hveem,Markku Laakso,Karen L. Mohlke,Andrew D. Morris,Colin N. A. Palmer,Peter P. Pramstaller,Igor Rudan,Igor Rudan,Eric J.G. Sijbrands,Lincoln Stein,Jaakko Tuomilehto,Jaakko Tuomilehto,André G. Uitterlinden,Mark Walker,Nicholas J. Wareham,Richard M. Watanabe,Gonçalo R. Abecasis,Bernhard O. Boehm,Harry Campbell,Mark J. Daly,Mark J. Daly,Andrew T. Hattersley,Frank B. Hu,Frank B. Hu,James B. Meigs,James S. Pankow,Oluf Pedersen,H-Erich Wichmann,Inês Barroso,Jose C. Florez,Timothy M. Frayling,Leif Groop,Leif Groop,Robert Sladek,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,James F. Wilson,Thomas Illig,Philippe Froguel,Philippe Froguel,Cornelia M. van Duijn,Kari Stefansson,Kari Stefansson,David Altshuler,Michael Boehnke,Mark I. McCarthy,Mark I. McCarthy,Mark I. McCarthy +183 more
TL;DR: By combining genome-wide association data from 8,130 individuals with type 2 diabetes and 38,987 controls of European descent and following up previously unidentified meta-analysis signals, 12 new T2D association signals are identified with combined P < 5 × 10−8.
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