Journal ArticleDOI
Progress and challenges in genome-wide association studies in humans
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TLDR
Genetic association data are now providing new routes to understanding the aetiology of disease, as well as new footholds on the long and difficult path to better treatment and disease prevention.Abstract:
After more than a decade of hope and hype, researchers are finally making inroads into understanding the genetic basis of many common human diseases. The use of genome-wide association studies has broken the logjam, enabling genetic variants at specific loci to be associated with particular diseases. Genetic association data are now providing new routes to understanding the aetiology of disease, as well as new footholds on the long and difficult path to better treatment and disease prevention.read more
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Common SNPs explain a large proportion of the heritability for human height
Jian Yang,Beben Benyamin,Brian P. McEvoy,Scott D. Gordon,Anjali K. Henders,Dale R. Nyholt,Pamela A. F. Madden,Andrew C. Heath,Nicholas G. Martin,Grant W. Montgomery,Michael E. Goddard,Peter M. Visscher +11 more
TL;DR: Evidence is provided that the remaining heritability is due to incomplete linkage disequilibrium between causal variants and genotyped SNPs, exacerbated by causal variants having lower minor allele frequency than the SNPs explored to date.
Journal ArticleDOI
Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease
Denise Harold,Richard Abraham,Paul Hollingworth,Rebecca Sims,Amy Gerrish,Marian L. Hamshere,Jaspreet Singh Pahwa,Valentina Moskvina,Kimberley Dowzell,Amy L. Williams,Nicola L. Jones,Charlene Thomas,Alexandra Stretton,Angharad R. Morgan,Simon Lovestone,John Powell,Petroula Proitsi,Michelle K. Lupton,Carol Brayne,David C. Rubinsztein,Michael Gill,Brian A. Lawlor,Aoibhinn Lynch,Kevin Morgan,Kristelle Brown,Peter Passmore,David Craig,Bernadette McGuinness,Stephen Todd,Clive Holmes,David M. A. Mann,A. David Smith,Seth Love,Patrick G. Kehoe,John Hardy,Simon Mead,Nick C. Fox,Martin N. Rossor,John Collinge,Wolfgang Maier,Frank Jessen,Britta Schürmann,Hendrik van den Bussche,Isabella Heuser,Johannes Kornhuber,Jens Wiltfang,Martin Dichgans,Lutz Frölich,Harald Hampel,Harald Hampel,Michael Hüll,Dan Rujescu,Alison Goate,John S. K. Kauwe,Carlos Cruchaga,Petra Nowotny,John C. Morris,Kevin Mayo,Kristel Sleegers,Karolien Bettens,Sebastiaan Engelborghs,Peter Paul De Deyn,Christine Van Broeckhoven,Gill Livingston,Nicholas Bass,Hugh Gurling,Andrew McQuillin,Rhian Gwilliam,Panagiotis Deloukas,Ammar Al-Chalabi,Christopher Shaw,Magda Tsolaki,Andrew B. Singleton,Rita Guerreiro,Thomas W. Mühleisen,Markus M. Nöthen,Susanne Moebus,Karl-Heinz Jöckel,Norman Klopp,H-Erich Wichmann,Minerva M. Carrasquillo,V. Shane Pankratz,Steven G. Younkin,Peter Holmans,Michael Conlon O'Donovan,Michael John Owen,Julie Williams +86 more
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Journal ArticleDOI
Integrating common and rare genetic variation in diverse human populations
David Altshuler,Richard A. Gibbs,Leena Peltonen,Emmanouil T. Dermitzakis,Stephen F. Schaffner,Fuli Yu,Penelope E. Bonnen,de Bakker Piw.,Panagiotis Deloukas,Stacey Gabriel,R. Gwilliam,Sarah E. Hunt,Michael Inouye,Xiaoming Jia,Aarno Palotie,Melissa Parkin,Pamela Whittaker,Kyle Chang,Alicia Hawes,Lora Lewis,Yanru Ren,D Wheeler,Donna M. Muzny,Chris P. Barnes,Katayoon Darvishi,Matthew E. Hurles,Joshua M. Korn,K. Kristiansson,Charles Lee,S A McCarrol,James Nemesh,Alon Keinan,Stephen B. Montgomery,Samuela Pollack,Alkes L. Price,Nicole Soranzo,Claudia Gonzaga-Jauregui,Verneri Anttila,Wendy Brodeur,Mark J. Daly,Stephen Leslie,Gil McVean,Loukas Moutsianas,Huy Nguyen,Qingrun Zhang,Ghori Mjr.,Ralph McGinnis,William M. McLaren,Fumihiko Takeuchi,Sharon R. Grossman,Ilya Shlyakhter,Elizabeth Hostetter,Pardis C. Sabeti,Clement Adebamowo,Morris W. Foster,Deborah R. Gordon,Julio Licinio,M C Manca,Patricia A. Marshall,Ichiro Matsuda,D Ngare,Vivian Ota Wang,D Reddy,Charles N. Rotimi,Charmaine D.M. Royal,Richard R. Sharp,Changqing Zeng,Lisa D. Brooks,Jean E. McEwen +68 more
TL;DR: An expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.
Journal ArticleDOI
Genome-wide association study indentifies variants at CLU and CR1 associated with Alzheimer’s disease
J-C Lambert,Simon Heath,G Even,Dominique Campion,K. Sleegers,Mikko Hiltunen,O Cambarros,Diana Zelenika,María J. Bullido,Béatrice Tavernier,Luc Letenneur,Karolien Bettens,Claudine Berr,Florence Pasquier,Nathalie Fievet,P Barbager-Gateau,S. Engelborghs,P.P. De Deyn,Ignacio Mateo,A Franck,Seppo Helisalmi,Elisa Porcellini,Olivier Hanon,M de Pancorbo,Corinne Lendon,Carole Dufouil,C Jaillard,Thierry Léveillard,Alvarez,Paolo Bosco,Michelangelo Mancuso,Francesco Panza,Benedetta Nacmias,Paola Bossù,Paola Piccardi,Giorgio Annoni,Davide Seripa,Daniela Galimberti,Didier Hannequin,Federico Licastro,Hilkka Soininen,Karen Ritchie,Hélène Blanché,J. F. Dartigues,Christophe Tzourio,Ivo Gut,Christine Van Broeckhoven,Annick Alpérovitch,P. Amouyel +48 more
Journal ArticleDOI
The Drosophila melanogaster Genetic Reference Panel
Trudy F. C. Mackay,Stephen Richards,Eric A. Stone,Antonio Barbadilla,Julien F. Ayroles,Julien F. Ayroles,Dianhui Zhu,Sònia Casillas,Yi Han,Michael M. Magwire,Julie M. Cridland,Mark F. Richardson,Robert R. H. Anholt,Maite G. Barrón,Crystal Bess,Kerstin P. Blankenburg,Mary Anna Carbone,David Castellano,Lesley S. Chaboub,Laura H Duncan,Zeke Harris,Mehwish Javaid,Joy Jayaseelan,Shalini N. Jhangiani,Katherine W. Jordan,Fremiet Lara,Faye Lawrence,Sandra L. Lee,Pablo Librado,Raquel S. Linheiro,Richard F. Lyman,Aaron J. Mackey,Mala Munidasa,Donna M. Muzny,Lynne V. Nazareth,Irene Newsham,Lora Perales,Ling-Ling Pu,Carson Qu,Miquel Ràmia,Jeffrey G. Reid,Stephanie M. Rollmann,Stephanie M. Rollmann,Julio Rozas,Nehad Saada,Lavanya Turlapati,Kim C. Worley,Yuanqing Wu,Akihiko Yamamoto,Yiming Zhu,Casey M. Bergman,Kevin R. Thornton,David Mittelman,Richard A. Gibbs +53 more
TL;DR: The Drosophila melanogaster Genetic Reference Panel is described, a community resource for analysis of population genomics and quantitative traits, which reveals reduced polymorphism in centromeric autosomal regions and the X chromosomes, evidence for positive and negative selection, and rapid evolution of the X chromosome.
References
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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
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 Wellcome Trust Case Control Consortium, U.K.
TL;DR: This article reports that the magazine's award for Research Leader of the Year was given to the Wellcome Trust Case Control Consortium which conducted a huge genetic study to look at the genetic causes for various diseases.
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
TL;DR: 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.
Journal ArticleDOI
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
Laura J. Scott,Karen L. Mohlke,Lori L. Bonnycastle,Cristen J. Willer,Yun Li,William L. Duren,Michael R. Erdos,Heather M. Stringham,Peter S. Chines,Anne U. Jackson,Ludmila Prokunina-Olsson,Chia-Jen Ding,Amy J. Swift,Narisu Narisu,Tianle Hu,Randall Pruim,Rui Xiao,Xiao-Yi Li,Karen N. Conneely,Nancy Riebow,Andrew G. Sprau,Maurine Tong,Peggy P. White,Kurt N. Hetrick,Michael W. Barnhart,Craig W. Bark,Janet L. Goldstein,Lee Watkins,Fang Xiang,Jouko Saramies,Thomas A. Buchanan,Richard M. Watanabe,Timo T. Valle,Leena Kinnunen,Gonçalo R. Abecasis,Elizabeth W. Pugh,Kimberly F. Doheny,Richard N. Bergman,Jaakko Tuomilehto,Francis S. Collins,Michael Boehnke +40 more
TL;DR: The number of T2D loci now confidently identified to at least 10 is confirmed, and it is confirmed that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T1D risk.
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