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

Author

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., Davison, Dan, Easton, Doug, Evans, David, Leung, Hin-Tak, Marchini, Jonathan L., Morris, Andrew P., Spencer, Chris C. A., Tobin, Martin D., 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, 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., 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., Dixon, Richard J., Mangino, Massimo, Stevens, Suzanne, Thompson, John R., 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., Lathrop, G. Mark, Connell, John, Dominiczak, Anna, 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, 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, Dunger, David B., Widmer, Barry, 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, 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, Stratton, Michael R., Rahman, Nazneen, Ban, Maria, Goris, An, Sawcer, Stephen J., Compston, Alastair, Conway, David, Jallow, Muminatou, Rockett, Kirk A., 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, Cardin, Niall J., Ferreira, Teresa, Pereira-Gale, Joanne, Hallgrimsdottir, Ingileif B., Howie, Bryan N., Su, Zhan, Teo, Yik Ying, Vukcevic, Damjan, Bentley, David, and Compston, Alistair

Subjects
Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Author(s): The Wellcome Trust Case Control Consortium; Management Committee; Paul R. Burton [1]; David G. Clayton [2]; Lon R. Cardon [3]; Nick Craddock [4]; Panos Deloukas [5]; Audrey Duncanson [6]; [...]

Published
2007
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4. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Author

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., Davison, Dan, Easton, Doug, Evans, David, Leung, Hin-Tak, Marchini, Jonathan L., Morris, Andrew P., Spencer, Chris C. A., Tobin, Martin D., 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, 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., 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., Dixon, Richard J., Mangino, Massimo, Stevens, Suzanne, Thompson, John R., 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., Lathrop, G. Mark, Connell, John, Dominiczak, Anna, 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, Dunger, David B., Widmer, Barry, 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, 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, Rockett, Kirk A., 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, Cardin, Niall J., Ferreira, Teresa, Pereira-Gale, Joanne, Hallgrimsdóttir, Ingileif B., Howie, Bryan N., Su, Zhan, Teo, Yik Ying, Vukcevic, Damjan, Bentley, David, Compston, Alistair, 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., Davison, Dan, Easton, Doug, Evans, David, Leung, Hin-Tak, Marchini, Jonathan L., Morris, Andrew P., Spencer, Chris C. A., Tobin, Martin D., 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, 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., 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., Dixon, Richard J., Mangino, Massimo, Stevens, Suzanne, Thompson, John R., 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., Lathrop, G. Mark, Connell, John, Dominiczak, Anna, 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, Dunger, David B., Widmer, Barry, 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, 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, Rockett, Kirk A., 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, Cardin, Niall J., Ferreira, Teresa, Pereira-Gale, Joanne, Hallgrimsdóttir, Ingileif B., Howie, Bryan N., Su, Zhan, Teo, Yik Ying, Vukcevic, Damjan, Bentley, David, and Compston, Alistair

Abstract

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 approx2,000 individuals for each of 7 major diseases and a shared set of approx3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 times 10-7: 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn'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 10-5 and 5 times 10-7) 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

5. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

Author

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 (Chair), Peter, Barrett, Jeffrey C, Davison, Dan, Donnelly, Peter, Easton, Doug, Evans, David M, Leung, Hin-Tak, Marchini, Jonathan L, Morris, Andrew P, Spencer, Chris CA, Tobin, Martin D, 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, Jones, Richard W, McArdle, Wendy L, Ring, Susan M, Strachan, David P, Pembrey, Marcus, Breen, Gerome, Clair, David St, Caesar, Sian, Gordon-Smith, Katharine, Jones, Lisa, Fraser, Christine, Green, Elaine K, Grozeva, Detelina, Hamshere, Marian L, Holmans, Peter A, Jones, Ian R, Kirov, George, Moskivina, Valentina, Nikolov, Ivan, O'Donovan, Michael C, Owen, Michael J, 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, Timothy D, Iles, Mark M, Maqbool, Azhar, Yuldasheva, Nadira, Hall, Alistair S, Braund, Peter S, Dixon, Richard J, Mangino, Massimo, Stevens, Suzanne, Thompson, John R, 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, Matthew, 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, Lathrop, Mark G, Connell, John, Dominiczak, Anna, 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, Bruce, Ian N, Donovan, Hannah, Eyre, Steve, Gilbert, Paul D, Hilder, Samantha L, Hinks, Anne M, John, Sally L, Potter, Catherine, Silman, Alan J, Symmons, Deborah PM, Thomson, Wendy, Worthington, Jane, Dunger, David B, Widmer, Barry, 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, Nicolas J, Zeggini, Eleftheria, 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 CL, Seal, Sheila, Stratton, Michael R, Rahman, Nazneen, Ban, Maria, Goris, An, Sawcer, Stephen J, Compston, Alastair, Conway, David, Jallow, Muminatou, Rockett, Kirk A, Bumpstead, Suzannah J, Chaney, Amy, Downes, Kate, Ghori, Mohammed JR, Gwilliam, Rhian, Hunt, Sarah E, Inouye, Michael, Keniry, Andrew, King, Emma, McGinnis, Ralph, Potter, Simon, Ravindrarajah, Rathi, Whittaker, Pamela, Widden, Claire, Withers, David, Cardin, Niall J, Ferreira, Teresa, Pereira-Gale, Joanne, Hallgrimsdóttir, Ingeleif B, Howie, Bryan N, Su, Zhan, Teo, Yik Ying, Vukcevic, Damjan, Bentley, David, Mitchell, Sarah L, Newby, Paul R, Brand, Oliver J, Carr-Smith, Jackie, Pearce, Simon H S, Gough, Stephen C L, McGinnis, R, Keniry, A, Deloukas, P, Reveille, John D, Zhou, Xiaodong, Sims, Anne-Marie, Dowling, Alison, Taylor, Jacqueline, Doan, Tracy, Davis, John C, Savage, Laurie, Ward, Michael M, Learch, Thomas L, Weisman, Michael H, 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 (Chair), Peter, Barrett, Jeffrey C, Davison, Dan, Donnelly, Peter, Easton, Doug, Evans, David M, Leung, Hin-Tak, Marchini, Jonathan L, Morris, Andrew P, Spencer, Chris CA, Tobin, Martin D, 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, Jones, Richard W, McArdle, Wendy L, Ring, Susan M, Strachan, David P, Pembrey, Marcus, Breen, Gerome, Clair, David St, Caesar, Sian, Gordon-Smith, Katharine, Jones, Lisa, Fraser, Christine, Green, Elaine K, Grozeva, Detelina, Hamshere, Marian L, Holmans, Peter A, Jones, Ian R, Kirov, George, Moskivina, Valentina, Nikolov, Ivan, O'Donovan, Michael C, Owen, Michael J, 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, Timothy D, Iles, Mark M, Maqbool, Azhar, Yuldasheva, Nadira, Hall, Alistair S, Braund, Peter S, Dixon, Richard J, Mangino, Massimo, Stevens, Suzanne, Thompson, John R, 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, Matthew, 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, Lathrop, Mark G, Connell, John, Dominiczak, Anna, 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, Bruce, Ian N, Donovan, Hannah, Eyre, Steve, Gilbert, Paul D, Hilder, Samantha L, Hinks, Anne M, John, Sally L, Potter, Catherine, Silman, Alan J, Symmons, Deborah PM, Thomson, Wendy, Worthington, Jane, Dunger, David B, Widmer, Barry, 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, Nicolas J, Zeggini, Eleftheria, 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 CL, Seal, Sheila, Stratton, Michael R, Rahman, Nazneen, Ban, Maria, Goris, An, Sawcer, Stephen J, Compston, Alastair, Conway, David, Jallow, Muminatou, Rockett, Kirk A, Bumpstead, Suzannah J, Chaney, Amy, Downes, Kate, Ghori, Mohammed JR, Gwilliam, Rhian, Hunt, Sarah E, Inouye, Michael, Keniry, Andrew, King, Emma, McGinnis, Ralph, Potter, Simon, Ravindrarajah, Rathi, Whittaker, Pamela, Widden, Claire, Withers, David, Cardin, Niall J, Ferreira, Teresa, Pereira-Gale, Joanne, Hallgrimsdóttir, Ingeleif B, Howie, Bryan N, Su, Zhan, Teo, Yik Ying, Vukcevic, Damjan, Bentley, David, Mitchell, Sarah L, Newby, Paul R, Brand, Oliver J, Carr-Smith, Jackie, Pearce, Simon H S, Gough, Stephen C L, McGinnis, R, Keniry, A, Deloukas, P, Reveille, John D, Zhou, Xiaodong, Sims, Anne-Marie, Dowling, Alison, Taylor, Jacqueline, Doan, Tracy, Davis, John C, Savage, Laurie, Ward, Michael M, Learch, Thomas L, and Weisman, Michael H

Abstract

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

6. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants.

Author

Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Samani NJ, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon-Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskivina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Ball SG, Balmforth AJ, Barrett JH, Bishop TD, Iles MM, Maqbool A, Yuldasheva N, Hall AS, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Matthew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop MG, Connell J, Dominiczak A, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hilder SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Newport M, Sirugo G, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Davison D, Ferreira T, Pereira-Gale J, Hallgrimsdo'ttir IB, Howie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Brown MA, Compston A, Farrall M, Hall AS, Hattersley AT, Hill AV, Parkes M, Pembrey M, Stratton MR, Mitchell SL, Newby PR, Brand OJ, Carr-Smith J, Pearce SH, McGinnis R, Keniry A, Deloukas P, Reveille JD, Zhou X, Sims AM, Dowling A, Taylor J, Doan T, Davis JC, Savage L, Ward MM, Learch TL, Weisman MH, and Brown M

Subjects
Aminopeptidases genetics, Breast Neoplasms epidemiology, Case-Control Studies, Chromosome Mapping, Genetics, Population, Genotype, Haplotypes genetics, Humans, Linkage Disequilibrium, Minor Histocompatibility Antigens, Multiple Sclerosis epidemiology, North America epidemiology, Polymerase Chain Reaction, Receptors, Immunologic genetics, Receptors, Interleukin genetics, Spondylitis, Ankylosing epidemiology, Thyroiditis, Autoimmune epidemiology, Autoimmunity genetics, Breast Neoplasms genetics, Multiple Sclerosis genetics, Polymorphism, Single Nucleotide genetics, Spondylitis, Ankylosing genetics, Thyroiditis, Autoimmune genetics
Abstract

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Published
2007
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