Journal ArticleDOI
Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes
Julius Gudmundsson,Patrick Sulem,Valgerdur Steinthorsdottir,Jon Thor Bergthorsson,Gudmar Thorleifsson,Andrei Manolescu,Thorunn Rafnar,Daniel F. Gudbjartsson,Bjarni A. Agnarsson,Adam Baker,Asgeir Sigurdsson,Kristrun R. Benediktsdottir,Margret Jakobsdottir,Thorarinn Blondal,Simon N. Stacey,Agnar Helgason,Steinunn Gunnarsdottir,Adalheidur Olafsdottir,Kari T. Kristinsson,Birgitta Birgisdottir,Shyamali Ghosh,Steinunn Thorlacius,Dana Magnusdottir,Gerdur Stefansdottir,Kristleifur Kristjansson,Yu Z. Bagger,Robert L. Wilensky,Muredach P. Reilly,Andrew D. Morris,Charlotte H. Kimber,Adebowale Adeyemo,Yuanxiu Chen,Jie Zhou,Wing-Yee So,Peter C.Y. Tong,Maggie C.Y. Ng,Torben Hansen,Gitte Andersen,Knut Borch-Johnsen,Knut Borch-Johnsen,Knut Borch-Johnsen,Torben Jørgensen,Alejandro Tres,Fernando Fuertes,M. Ruiz-Echarri,Laura Asín,Berta Saez,Erica Van Boven,Siem M. Klaver,Dorine W. Swinkels,Katja K.H. Aben,Theresa Graif,John Cashy,Brian K. Suarez,Onco Van Vierssen Trip,Michael L. Frigge,Carole Ober,Marten H. Hofker,Marten H. Hofker,Cisca Wijmenga,Cisca Wijmenga,Claus Christiansen,Daniel J. Rader,Colin N. A. Palmer,Charles N. Rotimi,Juliana C.N. Chan,Oluf Pedersen,Oluf Pedersen,Gunnar Sigurdsson,Rafn Benediktsson,Eirikur Jonsson,Gudmundur V. Einarsson,Jose I. Mayordomo,William J. Catalona,Lambertus A. Kiemeney,Rosa B. Barkardottir,Jeffrey R. Gulcher,Unnur Thorsteinsdottir,Augustine Kong,Kari Stefansson +79 more
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TLDR
Results from eight case-control groups demonstrate that this variant in TCF2 (HNF1β), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5, confers protection against type 2 diabetes.Abstract:
We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.read more
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Genome-wide association studies for complex traits: consensus, uncertainty and challenges
Mark I. McCarthy,Mark I. McCarthy,Gonçalo R. Abecasis,Lon R. Cardon,Lon R. Cardon,David Goldstein,Julian Little,John P. A. Ioannidis,John P. A. Ioannidis,Joel N. Hirschhorn,Joel N. Hirschhorn,Joel N. Hirschhorn +11 more
TL;DR: This Review highlights the knowledge gained, defines areas of emerging consensus, and describes the challenges that remain as researchers seek to obtain more complete descriptions of the susceptibility architecture of biomedical traits of interest and to translate the information gathered into improvements in clinical management.
Journal ArticleDOI
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
Eleftheria Zeggini,Laura J. Scott,Richa Saxena,Benjamin F. Voight,Jonathan Marchini,T Hu,de Bakker Piw.,de Bakker Piw.,de Bakker Piw.,Gonçalo R. Abecasis,Peter Almgren,Gregers S. Andersen,Kristin Ardlie,Kristina Bengtsson Boström,Richard N. Bergman,Lori L. Bonnycastle,Knut Borch-Johnsen,Knut Borch-Johnsen,Noël P. Burtt,H Chen,Peter S. Chines,Mark J. Daly,P Deodhar,Ding C-J.,Doney Asf.,William L. Duren,Katherine S. Elliott,Mike Erdos,Timothy M. Frayling,Rachel M. Freathy,Lauren Gianniny,Harald Grallert,Niels Grarup,Christopher J. Groves,Candace Guiducci,Torben Hansen,Christian Herder,Graham A. Hitman,Thomas Edward Hughes,Bo Isomaa,Anne U. Jackson,Torben Jørgensen,Augustine Kong,Kari Kubalanza,Finny G Kuruvilla,Finny G Kuruvilla,Johanna Kuusisto,Claudia Langenberg,Hana Lango,Torsten Lauritzen,Yun Li,Cecilia M. Lindgren,Cecilia M. Lindgren,Valeriya Lyssenko,Amanda F. Marvelle,Christine Meisinger,Kristian Midthjell,Karen L. Mohlke,Mario A. Morken,Andrew D. Morris,Narisu Narisu,Peter M. Nilsson,Katharine R. Owen,Palmer Cna.,Felicity Payne,Perry Jrb.,E Pettersen,Carl Platou,Inga Prokopenko,Inga Prokopenko,Lu Qi,Lu Qi,L Qin,Nigel W. Rayner,Nigel W. Rayner,Matthew G. Rees,J J Roix,A Sandbaek,Beverley M. Shields,Marketa Sjögren,Valgerdur Steinthorsdottir,Heather M. Stringham,Amy J. Swift,Gudmar Thorleifsson,Unnur Thorsteinsdottir,Nicholas J. Timpson,Nicholas J. Timpson,Tiinamaija Tuomi,Jaakko Tuomilehto,Mark Walker,Richard M. Watanabe,Michael N. Weedon,Cristen J. Willer,Thomas Illig,Kristian Hveem,Frank B. Hu,Frank B. Hu,Markku Laakso,Kari Stefansson,Oluf Pedersen,Oluf Pedersen,Nicholas J. Wareham,Inês Barroso,Andrew T. Hattersley,Francis S. Collins,Leif Groop,Leif Groop,Mark I. McCarthy,Mark I. McCarthy,Michael Boehnke,David Altshuler +110 more
TL;DR: The results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D, and detect at least six previously unknown loci with robust evidence for association.
Journal ArticleDOI
Genetic Mapping in Human Disease
TL;DR: The intellectual foundations of genetic mapping of Mendelian and complex traits in humans are discussed, lessons emerging from linkage analysis of MendELian diseases and genome-wide association studies of common diseases are examined, and questions and challenges that lie ahead are discussed.
Journal ArticleDOI
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
Paul Burton,David Clayton,Lon R. Cardon,Nicholas John Craddock,Panos Deloukas,Audrey Duncanson,Dominic P. Kwiatkowski,Dominic P. Kwiatkowski,Mark I. McCarthy,Willem H. Ouwehand,Willem H. Ouwehand,Nilesh J. Samani,John A. Todd,Peter Donnelly,Jeffrey C. Barrett,Dan Davison,Doug Easton,David M. Evans,H. T. Leung,Jonathan Marchini,Jonathan Marchini,Andrew P. Morris,Chris C. A. Spencer,Martin D. Tobin,Antony P. Attwood,Antony P. Attwood,James P. Boorman,James P. Boorman,Barbara Cant,Ursula Everson,Judith M. Hussey,Jennifer Jolley,Alexandra S. Knight,Kerstin Koch,Elizabeth Meech,Sarah Nutland,Christopher Prowse,Helen Stevens,Niall C. Taylor,Graham R. Walters,Neil Walker,Nicholas A. Watkins,Nicholas A. Watkins,Thilo Winzer,Richard Jones,Wendy L. McArdle,Susan M. Ring,David P. Strachan,Marcus Pembrey,Gerome Breen,David St Clair,Sian Caesar,Katharine Gordon-Smith,Katharine Gordon-Smith,Lisa Jones,Christine Fraser,Elaine K. Green,Detelina Grozeva,Marian L. Hamshere,Peter Holmans,Ian Jones,George Kirov,Valentina Moskivina,Ivan Nikolov,Michael Conlon O'Donovan,Michael John Owen,David A. Collier,Amanda Elkin,Anne Farmer,Richard Williamson,Peter McGuffin,Allan H. Young,I. Nicol Ferrier,Stephen G. Ball,Anthony J. Balmforth,Jennifer H. Barrett,Timothy Bishop,Mark M. Iles,Azhar Maqbool,Nadira Yuldasheva,Alistair S. Hall,Peter S. Braund,Richard J. Dixon,Massimo Mangino,Suzanne Stevens,John R. Thompson,Francesca Bredin,Mark Tremelling,Miles Parkes,Hazel E. Drummond,Charlie W. Lees,Elaine R. Nimmo,Jack Satsangi,Sheila A. Fisher,Alastair Forbes,Cathryn M. Lewis,Clive M. Onnie,Natalie J. Prescott,Jeremy D. Sanderson,Christopher G Matthew,Jamie Barbour,M. Khalid Mohiuddin,Catherine E. Todhunter,John C. Mansfield,Tariq Ahmad,Fraser Cummings,Derek P. Jewell,John Webster,Morris J. Brown,Mark Lathrop,John M. C. Connell,Anna F. Dominiczak,Carolina A. Braga Marcano,Beverley Burke,Richard Dobson,Johannie Gungadoo,Kate L. Lee,Patricia B. Munroe,Stephen Newhouse,Abiodun Onipinla,Chris Wallace,Mingzhan Xue,Mark J. Caulfield,Martin Farrall,Anne Barton,Ian N. Bruce,Hannah Donovan,Steve Eyre,Paul D. Gilbert,Samantha L Hilder,Anne Hinks,Sally John,Catherine Potter,Alan J. Silman,Deborah P M Symmons,Wendy Thomson,Jane Worthington,David B. Dunger,Barry Widmer,Timothy M. Frayling,Rachel M. Freathy,Hana Lango,John R. B. Perry,Beverley M. Shields,Michael N. Weedon,Andrew T. Hattersley,Graham A. Hitman,Mark Walker,Kate S. Elliott,Christopher J. Groves,Cecilia M. Lindgren,Nigel W. Rayner,N J Timpson,Eleftheria Zeggini,Melanie J. Newport,Giorgio Sirugo,Emily J. Lyons,Fredrik O. Vannberg,Adrian V. S. Hill,Linda A. Bradbury,C Farrar,J J Pointon,Paul Wordsworth,Matthew A. Brown,Matthew A. Brown,Jayne A. Franklyn,Joanne M. Heward,Matthew J. Simmonds,Stephen C. L. Gough,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Maria Ban,An Goris,Stephen Sawcer,Alastair Compston,David J. Conway,Muminatou Jallow,Kirk A. Rockett,Suzannah Bumpstead,Amy Chaney,Kate Downes,Kate Downes,Mohammed J. R. Ghori,Rhian Gwilliam,Sarah E. Hunt,Michael Inouye,Andrew Keniry,Emma King,Ralph McGinnis,Simon C. Potter,Rathi Ravindrarajah,Pamela Whittaker,Claire Widden,David Withers,Niall Cardin,Teresa Ferreira,Joanne Pereira-Gale,Ingeleif B. Hallgrimsdottir,Bryan Howie,Zhan Su,Yik Ying Teo,Damjan Vukcevic,David Bentley,David Bentley,Sarah L Mitchell,Paul R. Newby,Oliver J. Brand,Jackie Carr-Smith,Simon H. S. Pearce,Stephen C L Gough,R McGinnis,A Keniry,Panagiotis Deloukas,John D. Reveille,Xiaodong Zhou,A. M. Sims,Alison Dowling,Jacqueline Taylor,Tracy Doan,John C. Davis,L. Savage,Michael M. Ward,Thomas Learch,Michael H. Weisman +224 more
TL;DR: In this paper, the authors report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirm the previously reported association of AITD with TSHR and FCRL3.
Journal ArticleDOI
Human genetic variation and its contribution to complex traits.
TL;DR: Most common SNPs have now been assessed in genome-wide studies for statistical associations with many complex traits, including many important common diseases, and only a limited amount of the heritable component of any complex trait has been identified.
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Genome-wide association study of prostate cancer identifies a second risk locus at 8q24
Meredith Yeager,Nick Orr,Richard B. Hayes,Kevin B. Jacobs,Peter Kraft,Sholom Wacholder,Mark J Minichiello,Paul Fearnhead,Kai Yu,Nilanjan Chatterjee,Zhaoming Wang,Zhaoming Wang,Robert W Welch,Robert W Welch,Brian Staats,Brian Staats,Eugenia E. Calle,Heather Spencer Feigelson,Michael J. Thun,Carmen Rodriguez,Demetrius Albanes,Jarmo Virtamo,Stephanie J. Weinstein,Fredrick R. Schumacher,Edward Giovannucci,Walter C. Willett,Geraldine Cancel-Tassin,Olivier Cussenot,Antoine Valeri,Gerald L. Andriole,Edward P. Gelmann,Margaret A. Tucker,Daniela S. Gerhard,Joseph F. Fraumeni,Robert N. Hoover,David J. Hunter,David J. Hunter,Stephen J. Chanock,Gilles Thomas +38 more
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Journal ArticleDOI
Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24.
Julius Gudmundsson,Patrick Sulem,Andrei Manolescu,Laufey T. Amundadottir,Daniel F. Gudbjartsson,Agnar Helgason,Thorunn Rafnar,Jon Thor Bergthorsson,Bjarni A. Agnarsson,Adam Baker,Asgeir Sigurdsson,Kristrun R. Benediktsdottir,Margret Jakobsdottir,Jianfeng Xu,Thorarinn Blondal,Jelena Kostic,Jielin Sun,Shyamali Ghosh,Simon N. Stacey,Magali Mouy,Jona Saemundsdottir,Valgerdur M Backman,Kristleifur Kristjansson,Alejandro Tres,Alan W. Partin,Marjo T Albers-Akkers,Javier Godino-Ivan Marcos,Patrick C. Walsh,Dorine W. Swinkels,Sebastian Navarrete,Sarah D. Isaacs,Katja K.H. Aben,Theresa Graif,John Cashy,M. Ruiz-Echarri,Kathleen E. Wiley,Brian K. Suarez,J. Alfred Witjes,Mike Frigge,Carole Ober,Eirikur Jonsson,Gudmundur V. Einarsson,Jose I. Mayordomo,Lambertus A. Kiemeney,William B. Isaacs,William J. Catalona,Rosa B. Barkardottir,Jeffrey R. Gulcher,Unnur Thorsteinsdottir,Augustine Kong,Kari Stefansson +50 more
TL;DR: A second genetic variant in the 8q24 region that, in conjunction with another variant recently discovered, accounts for about 11%–13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans is reported.
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