Мобильная версия

Доступно журналов:

3 288

Доступно статей:

3 891 637

 
Расширенный поиск

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Burton, Paul R.; Clayton, David G.; Cardon, Lon R.; Craddock, Nick; Deloukas, Panos; Duncanson, Audrey; Kwiatkowski, Dominic P.; McCarthy, Mark I.; Ouwehand, Willem H.; Samani, Nilesh J.; Todd, John A.; Donnelly, Peter; Barrett, Jeffrey C.; Burton, Paul R.; Davison, Dan; Donnelly, Peter; Easton, Doug; Evans, David; Leung, Hin-Tak; Marchini, Jonathan L.; Morris, Andrew P.; Spencer, Chris C. A.; Tobin, Martin D.; Cardon, Lon R.; Clayton, David G.; Attwood, Antony P.; Boorman, James P.; Cant, Barbara; Everson, Ursula; Hussey, Judith M.; Jolley, Jennifer D.; Knight, Alexandra S.; Koch, Kerstin; Meech, Elizabeth; Nutland, Sarah; Prowse, Christopher V.; Stevens, Helen E.; Taylor, Niall C.; Walters, Graham R.; Walker, Neil M.; Watkins, Nicholas A.; Winzer, Thilo; Todd, John A.; Ouwehand, Willem H.; Jones, Richard W.; McArdle, Wendy L.; Ring, Susan M.; Strachan, David P.; Pembrey, Marcus; Breen, Gerome; St Clair, David; Caesar, Sian; Gordon-Smith, Katherine; Jones, Lisa; Fraser, Christine; Green, Elaine K.; Grozeva, Detelina; Hamshere, Marian L.; Holmans, Peter A.; Jones, Ian R.; Kirov, George; Moskvina, Valentina; Nikolov, Ivan; O'Donovan, Michael C.; Owen, Michael J.; Craddock, Nick; Collier, David A.; Elkin, Amanda; Farmer, Anne; Williamson, Richard; McGuffin, Peter; Young, Allan H.; Ferrier, I. Nicol; Ball, Stephen G.; Balmforth, Anthony J.; Barrett, Jennifer H.; Bishop, D. Timothy; Iles, Mark M.; Maqbool, Azhar; Yuldasheva, Nadira; Hall, Alistair S.; Braund, Peter S.; Burton, Paul R.; Dixon, Richard J.; Mangino, Massimo; Stevens, Suzanne; Tobin, Martin D.; Thompson, John R.; Samani, Nilesh J.; Bredin, Francesca; Tremelling, Mark; Parkes, Miles; Drummond, Hazel; Lees, Charles W.; Nimmo, Elaine R.; Satsangi, Jack; Fisher, Sheila A.; Forbes, Alastair; Lewis, Cathryn M.; Onnie, Clive M.; Prescott, Natalie J.; Sanderson, Jeremy; Mathew, Christopher G.; Barbour, Jamie; Mohiuddin, M. Khalid; Todhunter, Catherine E.; Mansfield, John C.; Ahmad, Tariq; Cummings, Fraser R.; Jewell, Derek P.; Webster, John; Brown, Morris J.; Clayton, David G.; Lathrop, G. Mark; Connell, John; Dominiczak, Anna; Samani, Nilesh J.; Marcano, Carolina A. Braga; Burke, Beverley; Dobson, Richard; Gungadoo, Johannie; Lee, Kate L.; Munroe, Patricia B.; Newhouse, Stephen J.; Onipinla, Abiodun; Wallace, Chris; Xue, Mingzhan; Caulfield, Mark; Farrall, Martin; Barton, Anne; and Genomics (BRAGGS), The Biologics in RA Genetics; Bruce, Ian N.; Donovan, Hannah; Eyre, Steve; Gilbert, Paul D.; Hider, Samantha L.; Hinks, Anne M.; John, Sally L.; Potter, Catherine; Silman, Alan J.; Symmons, Deborah P. M.; Thomson, Wendy; Worthington, Jane; Clayton, David G.; Dunger, David B.; Nutland, Sarah; Stevens, Helen E.; Walker, Neil M.; Widmer, Barry; Todd, John A.; Frayling, Timothy M.; Freathy, Rachel M.; Lango, Hana; Perry, John R. B.; Shields, Beverley M.; Weedon, Michael N.; Hattersley, Andrew T.; Hitman, Graham A.; Walker, Mark; Elliott, Kate S.; Groves, Christopher J.; Lindgren, Cecilia M.; Rayner, Nigel W.; Timpson, Nicholas J.; Zeggini, Eleftheria; McCarthy, Mark I.; Newport, Melanie; Sirugo, Giorgio; Lyons, Emily; Vannberg, Fredrik; Hill, Adrian V. S.; Bradbury, Linda A.; Farrar, Claire; Pointon, Jennifer J.; Wordsworth, Paul; Brown, Matthew A.; Franklyn, Jayne A.; Heward, Joanne M.; Simmonds, Matthew J.; Gough, Stephen C. L.; Seal, Sheila; Susceptibility Collaboration (UK), Breast Cancer; Stratton, Michael R.; Rahman, Nazneen; Ban, Maria; Goris, An; Sawcer, Stephen J.; Compston, Alastair; Conway, David; Jallow, Muminatou; Newport, Melanie; Sirugo, Giorgio; Rockett, Kirk A.; Kwiatkowski, Dominic P.; Bumpstead, Suzannah J.; Chaney, Amy; Downes, Kate; Ghori, Mohammed J. R.; Gwilliam, Rhian; Hunt, Sarah E.; Inouye, Michael; Keniry, Andrew; King, Emma; McGinnis, Ralph; Potter, Simon; Ravindrarajah, Rathi; Whittaker, Pamela; Widden, Claire; Withers, David; Deloukas, Panos; Leung, Hin-Tak; Nutland, Sarah; Stevens, Helen E.; Walker, Neil M.; Todd, John A.; Easton, Doug; Clayton, David G.; Burton, Paul R.; Tobin, Martin D.; Barrett, Jeffrey C.; Evans, David; Morris, Andrew P.; Cardon, Lon R.; Cardin, Niall J.; Davison, Dan; Ferreira, Teresa; Pereira-Gale, Joanne; Hallgrimsdóttir, Ingileif B.; Howie, Bryan N.; Marchini, Jonathan L.; Spencer, Chris C. A.; Su, Zhan; Teo, Yik Ying; Vukcevic, Damjan; Donnelly, Peter; Bentley, David; Brown, Matthew A.; Cardon, Lon R.; Caulfield, Mark; Clayton, David G.; Compston, Alistair; Craddock, Nick; Deloukas, Panos; Donnelly, Peter; Farrall, Martin; Gough, Stephen C. L.; Hall, Alistair S.; Hattersley, Andrew T.; Hill, Adrian V. S.; Kwiatkowski, Dominic P.; Mathew, Christopher G.; McCarthy, Mark I.; Ouwehand, Willem H.; Parkes, Miles; Pembrey, Marcus; Rahman, Nazneen; Samani, Nilesh J.; Stratton, Michael R.; Todd, John A.; Worthington, Jane; The Wellcome Trust Case Control Consortium; Management Committee; Data and Analysis Committee; UK Blood Services and University of Cambridge Controls; 1958 Birth Cohort Controls; Bipolar Disorder; Coronary Artery Disease; Crohnâ s Disease; Hypertension; Rheumatoid Arthritis; Type 1 Diabetes; Type 2 Diabetes; Tuberculosis; Ankylosing Spondylitis; Autoimmune Thyroid Disease; Breast Cancer; Multiple Sclerosis; Gambian Controls; DNA, Genotyping, Data QC and Informatics; Statistics; Primary Investigators
Журнал: Nature
Дата: 2007

Показать метаданные

Аннотация:

There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined â ¼2,000 individuals for each of 7 major diseases and a shared set of â ¼3,000 controls. Case-control comparisons identified 24 independent association signals at Pâ <â 5â Ã â 10<sup>-7</sup>: 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohnâ s disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals (including 58 loci with single-point P values between 10<sup>-5</sup> and 5â Ã â 10<sup>-7</sup>) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has 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 the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.
Icon
Читать
4.109Мб