Jose C Florez1. 1. Simches Research Building-CPZN 5.250, 185 Cambridge Street, Diabetes Unit/Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. jcflorez@partners.org
Abstract
CONTEXT: Over the last few months, genome-wide association studies have contributed significantly to our understanding of the genetic architecture of type 2 diabetes. If and how this information will impact clinical practice is not yet clear. EVIDENCE ACQUISITION: Primary papers reporting genome-wide association studies in type 2 diabetes or establishing a reproducible association for specific candidate genes were compiled. Further information was obtained from background articles, authoritative reviews, and relevant meeting conferences and abstracts. EVIDENCE SYNTHESIS: As many as 17 genetic loci have been convincingly associated with type 2 diabetes; 14 of these were not previously known, and most of them were unsuspected. The associated polymorphisms are common in populations of European descent but have modest effects on risk. These loci highlight new areas for biological exploration and allow the initiation of experiments designed to develop prediction models and test possible pharmacogenetic and other applications. CONCLUSIONS: Although substantial progress in our knowledge of the genetic basis of type 2 diabetes is taking place, these new discoveries represent but a small proportion of the genetic variation underlying the susceptibility to this disorder. Major work is still required to identify the causal variants, test their role in disease prediction and ascertain their therapeutic implications.
CONTEXT: Over the last few months, genome-wide association studies have contributed significantly to our understanding of the genetic architecture of type 2 diabetes. If and how this information will impact clinical practice is not yet clear. EVIDENCE ACQUISITION: Primary papers reporting genome-wide association studies in type 2 diabetes or establishing a reproducible association for specific candidate genes were compiled. Further information was obtained from background articles, authoritative reviews, and relevant meeting conferences and abstracts. EVIDENCE SYNTHESIS: As many as 17 genetic loci have been convincingly associated with type 2 diabetes; 14 of these were not previously known, and most of them were unsuspected. The associated polymorphisms are common in populations of European descent but have modest effects on risk. These loci highlight new areas for biological exploration and allow the initiation of experiments designed to develop prediction models and test possible pharmacogenetic and other applications. CONCLUSIONS: Although substantial progress in our knowledge of the genetic basis of type 2 diabetes is taking place, these new discoveries represent but a small proportion of the genetic variation underlying the susceptibility to this disorder. Major work is still required to identify the causal variants, test their role in disease prediction and ascertain their therapeutic implications.
Authors: Paul I W de Bakker; Roman Yelensky; Itsik Pe'er; Stacey B Gabriel; Mark J Daly; David Altshuler Journal: Nat Genet Date: 2005-10-23 Impact factor: 38.330
Authors: Alkes L Price; Nick J Patterson; Robert M Plenge; Michael E Weinblatt; Nancy A Shadick; David Reich Journal: Nat Genet Date: 2006-07-23 Impact factor: 38.330
Authors: Itsik Pe'er; Paul I W de Bakker; Julian Maller; Roman Yelensky; David Altshuler; Mark J Daly Journal: Nat Genet Date: 2006-05-21 Impact factor: 38.330
Authors: Struan F A Grant; Gudmar Thorleifsson; Inga Reynisdottir; Rafn Benediktsson; Andrei Manolescu; Jesus Sainz; Agnar Helgason; Hreinn Stefansson; Valur Emilsson; Anna Helgadottir; Unnur Styrkarsdottir; Kristinn P Magnusson; G Bragi Walters; Ebba Palsdottir; Thorbjorg Jonsdottir; Thorunn Gudmundsdottir; Arnaldur Gylfason; Jona Saemundsdottir; Robert L Wilensky; Muredach P Reilly; Daniel J Rader; Yu Bagger; Claus Christiansen; Vilmundur Gudnason; Gunnar Sigurdsson; Unnur Thorsteinsdottir; Jeffrey R Gulcher; Augustine Kong; Kari Stefansson Journal: Nat Genet Date: 2006-01-15 Impact factor: 38.330
Authors: Lori L Bonnycastle; Cristen J Willer; Karen N Conneely; Anne U Jackson; Cecily P Burrill; Richard M Watanabe; Peter S Chines; Narisu Narisu; Laura J Scott; Sareena T Enloe; Amy J Swift; William L Duren; Heather M Stringham; Michael R Erdos; Nancy L Riebow; Thomas A Buchanan; Timo T Valle; Jaakko Tuomilehto; Richard N Bergman; Karen L Mohlke; Michael Boehnke; Francis S Collins Journal: Diabetes Date: 2006-09 Impact factor: 9.461
Authors: Jacek Bochenski; Grzegorz Placha; Krzysztof Wanic; Maciej Malecki; Jacek Sieradzki; James H Warram; Andrzej S Krolewski Journal: Diabetes Date: 2006-09 Impact factor: 9.461
Authors: Jose C Florez; Kathleen A Jablonski; Nick Bayley; Toni I Pollin; Paul I W de Bakker; Alan R Shuldiner; William C Knowler; David M Nathan; David Altshuler Journal: N Engl J Med Date: 2006-07-20 Impact factor: 91.245
Authors: Takafumi Tsuchiya; Peter E H Schwarz; Laura Del Bosque-Plata; M Geoffrey Hayes; Christian Dina; Philippe Froguel; G Wayne Towers; Sabine Fischer; Theodora Temelkova-Kurktschiev; Hannes Rietzsch; Juergen Graessler; Josef Vcelák; Daniela Palyzová; Thomas Selisko; Bela Bendlová; Jan Schulze; Ulrich Julius; Markolf Hanefeld; Michael N Weedon; Julie C Evans; Timothy M Frayling; Andrew T Hattersley; Marju Orho-Melander; Leif Groop; Maciej T Malecki; Torben Hansen; Oluf Pedersen; Tasha E Fingerlin; Michael Boehnke; Craig L Hanis; Nancy J Cox; Graeme I Bell Journal: Mol Genet Metab Date: 2006-07-11 Impact factor: 4.797