Journal ArticleDOI
Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels
Richa Saxena,Benjamin F. Voight,Valeriya Lyssenko,Noël P. Burtt,Paul I.W. de Bakker,Hong Chen,Jeffrey J. Roix,Sekar Kathiresan,Joel N. Hirschhorn,Mark J. Daly,Thomas E. Hughes,Leif Groop,David Altshuler,Peter Almgren,Jose C. Florez,Joanne M. Meyer,Kristin Ardlie,Kristina Bengtsson Boström,Bo Isomaa,Guillaume Lettre,Ulf Lindblad,Helen N. Lyon,Olle Melander,Christopher Newton-Cheh,Peter Nilsson,Marju Orho-Melander,Lennart Råstam,Elizabeth K. Speliotes,Marja-Riitta Taskinen,Tiinamaija Tuomi,Candace Guiducci,Anna Berglund,Joyce Carlson,Lauren Gianniny,Rachel Hackett,Liselotte Hall,Johan Holmkvist,Esa Laurila,Marketa Sjögren,Maria Sterner,Aarti Surti,Margareta Svensson,Malin Svensson,Ryan Tewhey,Brendan Blumenstiel,Melissa Parkin,Matthew DeFelice,Rachel Barry,Wendy Brodeur,Jody Camarata,Nancy Chia,Mary Fava,John G. Gibbons,Bob Handsaker,Claire M. Healy,Kieu Nguyen,Casey Gates,Carrie Sougnez,Diane Gage,Marcia M. Nizzari,Stacey Gabriel,Gung-Wei Chirn,Qicheng Ma,Hemang Parikh,Delwood Richardson,Darrell O. Ricke,Shaun Purcell +66 more
TLDR
The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.Abstract:
New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.read more
Citations
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PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Shaun Purcell,Shaun Purcell,Benjamin M. Neale,Benjamin M. Neale,Kathe Todd-Brown,Lori Thomas,Manuel A. R. Ferreira,David Bender,David Bender,Julian Maller,Julian Maller,Pamela Sklar,Pamela Sklar,Paul I.W. de Bakker,Paul I.W. de Bakker,Mark J. Daly,Mark J. Daly,Pak C. Sham +17 more
TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
Journal ArticleDOI
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Paul Burton,David Clayton,Lon R. Cardon,Nicholas John Craddock,Panos Deloukas,Audrey Duncanson,Dominic P. Kwiatkowski,Mark I. McCarthy,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,Andrew P. Morris,Chris C. A. Spencer,Martin D. Tobin,Antony P. Attwood,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,Thilo Winzer,Richard Jones,Wendy L. McArdle,Susan M. Ring,David P. Strachan,Marcus Pembrey,Gerome Breen,David St Clair,Sian Caesar,Katherine Gordon-Smith,Lisa Jones,Christine Fraser,Elaine K. Green,Detelina Grozeva,Marian L. Hamshere,Peter Holmans,Ian Jones,George Kirov,Valentina Moskvina,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,D. 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. Mathew,Jamie Barbour,M. Khalid Mohiuddin,Catherine E. Todhunter,John C. Mansfield,Tariq Ahmad,Fraser Cummings,Derek P. Jewell,John Webster,Morris J. Brown,G. 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. Hider,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,Nicholas 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,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,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,Ingileif B. Hallgrímsdóttir,Bryan Howie,Zhan Su,Yik Ying Teo,Damjan Vukcevic,David Bentley,A Compston +195 more
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Journal ArticleDOI
Biological, clinical and population relevance of 95 loci for blood lipids
Tanya M. Teslovich,Kiran Musunuru,Albert V. Smith,Andrew C. Edmondson,Ioannis M. Stylianou,Masahiro Koseki,James P. Pirruccello,James P. Pirruccello,James P. Pirruccello,Samuli Ripatti,Daniel I. Chasman,Cristen J. Willer,Christopher T. Johansen,Sigrid W. Fouchier,Aaron Isaacs,Gina M. Peloso,Maja Barbalić,Sally L. Ricketts,Joshua C. Bis,Yurii S. Aulchenko,Gudmar Thorleifsson,Mary F. Feitosa,John C. Chambers,Marju Orho-Melander,Olle Melander,Toby Johnson,Xiaohui Li,Xiuqing Guo,Mingyao Li,Yoon Shin Cho,Min Jin Go,Young Jin Kim,Jong-Young Lee,Taesung Park,Kyunga Kim,Xueling Sim,Rick Twee-Hee Ong,Damien C. Croteau-Chonka,Leslie A. Lange,Joshua D. Smith,Kijoung Song,Jing Hua Zhao,Xin Yuan,Jian'an Luan,Claudia Lamina,Andreas Ziegler,Weihua Zhang,Robert Y.L. Zee,Alan F. Wright,Jacqueline C. M. Witteman,James F. Wilson,Gonneke Willemsen,H.-Erich Wichmann,John Whitfield,Dawn M. Waterworth,Nicholas J. Wareham,Gérard Waeber,Peter Vollenweider,Benjamin F. Voight,Benjamin F. Voight,Veronique Vitart,André G. Uitterlinden,Manuela Uda,Jaakko Tuomilehto,John R. Thompson,Toshiko Tanaka,Ida Surakka,Heather M. Stringham,Tim D. Spector,Nicole Soranzo,Nicole Soranzo,Johannes H. Smit,Juha Sinisalo,Kaisa Silander,Eric J.G. Sijbrands,Angelo Scuteri,James Scott,David Schlessinger,Serena Sanna,Veikko Salomaa,Juha Saharinen,Chiara Sabatti,Aimo Ruokonen,Igor Rudan,Lynda M. Rose,Robert Roberts,Mark J. Rieder,Bruce M. Psaty,Peter P. Pramstaller,Irene Pichler,Markus Perola,Brenda W.J.H. Penninx,Nancy L. Pedersen,Cristian Pattaro,Alex N. Parker,Guillaume Paré,Ben A. Oostra,Christopher J. O'Donnell,Markku S. Nieminen,Deborah A. Nickerson,Grant W. Montgomery,Thomas Meitinger,Ruth McPherson,Mark I. McCarthy,Wendy L. McArdle,David Masson,Nicholas G. Martin,Fabio Marroni,Massimo Mangino,Patrik K. E. Magnusson,Gavin Lucas,Robert Luben,Ruth J. F. Loos,Marja-Liisa Lokki,Guillaume Lettre,Claudia Langenberg,Lenore J. Launer,Edward G. Lakatta,Reijo Laaksonen,Kirsten Ohm Kyvik,Florian Kronenberg,Inke R. Koenig,Kay-Tee Khaw,Jaakko Kaprio,Lee M. Kaplan,Åsa Johansson,Marjo-Riitta Järvelin,A. Cecile J.W. Janssens,Erik Ingelsson,Wilmar Igi,G. Kees Hovingh,Jouke-Jan Hottenga,Albert Hofman,Andrew A. Hicks,Christian Hengstenberg,Iris M. Heid,Caroline Hayward,Aki S. Havulinna,Nicholas D. Hastie,Tamara B. Harris,Talin Haritunians,Alistair S. Hall,Ulf Gyllensten,Candace Guiducci,Leif Groop,Leif Groop,Elena Gonzalez,Christian Gieger,Nelson B. Freimer,Luigi Ferrucci,Jeanette Erdmann,Paul Elliott,Kenechi Ejebe,Angela Doering,Anna F. Dominiczak,Serkalem Demissie,Panagiotis Deloukas,Eco J. C. de Geus,Ulf de Faire,Gabriel Crawford,Francis S. Collins,Yii-Der Ida Chen,Mark J. Caulfield,Harry Campbell,Noël P. Burtt,Lori L. Bonnycastle,Dorret I. Boomsma,S. Matthijs Boekholdt,Richard N. Bergman,Inês Barroso,Stefania Bandinelli,Christie M. Ballantyne,Themistocles L. Assimes,Themistocles L. Assimes,Thomas Quertermous,Thomas Quertermous,David Altshuler,David Altshuler,Mark Seielstad,Tien Yin Wong,E-Shyong Tai,Alan B. Feranil,Christopher W. Kuzawa,Christopher W. Kuzawa,Linda S. Adair,Herman A. Taylor,Ingrid B. Borecki,Stacey Gabriel,James G. Wilson,Hilma Holm,Unnur Thorsteinsdottir,Vilmundur Gudnason,Ronald M. Krauss,Karen L. Mohlke,Jose M. Ordovas,Patricia B. Munroe,Jaspal S. Kooner,Alan R. Tall,Robert A. Hegele,John J.P. Kastelein,Eric E. Schadt,Jerome I. Rotter,Eric Boerwinkle,David P. Strachan,Vincent Mooser,Kari Stefansson,Muredach P. Reilly,Nilesh J. Samani,Heribert Schunkert,L. Adrienne Cupples,Manjinder S. Sandhu,Manjinder S. Sandhu,Paul M. Ridker,Daniel J. Rader,Cornelia M. van Duijn,Leena Peltonen,Gonçalo R. Abecasis,Michael Boehnke,Sekar Kathiresan +218 more
TL;DR: The results identify several novel loci associated with plasma lipids that are also associated with CAD and provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
Journal ArticleDOI
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
The NHGRI GWAS Catalog, a curated resource of SNP-trait associations
Danielle Welter,Jacqueline A. L. MacArthur,Joannella Morales,Tony Burdett,Peggy Hall,Heather Junkins,Alan Klemm,Paul Flicek,Teri A. Manolio,Lucia A. Hindorff,Helen Parkinson +10 more
TL;DR: A number of recent improvements to theNHGRI Catalog of Published Genome-Wide Association Studies are presented, including novel ways for users to interact with the Catalog and changes to the curation infrastructure.
References
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