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

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
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
confirmation, disease, single-nucleotide polymorphisms, susceptibility loci, children, population-structure, genetic association, risk, crohn-disease, project, blood, susceptibility, cancer, genome-wide association, ankylosing-spondylitis, graves-disease, association, aminopeptidase
1061-4036
1329-1337
Newport, Melanie
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Sirugo, Giorgio
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Lyons, Emily
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Vannberg, Fredrik
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Hill, Adrian V.S.
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Bradbury, Linda A.
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Farrar, Claire
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Pointon, Jennifer J.
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Wordsworth, Paul
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Brown, Matthew A.
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Franklyn, Jayne A.
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Heward, Joanne M.
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Simmonds, Matthew J.
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Gough, Stephen C.
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Seal, Sheila
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Stratton, Michael R.
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Rahman, Nazneen
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Ban, Maria
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Goris, An
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Sawcer, Stephen J.
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Compston, Alastair
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Conway, David
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Jallow, Muminatou
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Rockett, Kirk A.
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Kwiatkowski, Dominic P.
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Bumpstead, Suzannah J.
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Chaney, Amy
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Downes, Kate
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Ghori, Mohammed J.R.
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Gwilliam, Rhian
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Hunt, Sarah E.
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Inouye, Michael
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Keniry, Andrew
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King, Emma
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McGinnis, Ralph
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Potter, Simon
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Ravindrarajah, Rathi
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Whittaker, Pamela
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Widden, Claire
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Withers, David
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Deloukas, Panos
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Leung, Hin-Tak S.
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Stevens, Helen E.
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Walker, Neil M.
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Todd, John A.
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Easton, Doug
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Clayton, David G.
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Burton, Paul R.
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Tobin, Martin D.
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Barrett, Jeffrey C.
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Evans, David M.
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Morris, Andrew P.
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Cardon, Lon R.
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Cardin, Niall J.
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Davison, Dan
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Ferreira, Teresa
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Pereira-Gale, Joanne
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Howie, Bryan N.
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Marchini, Jonathan L.
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Spencer, Chris C.A.
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Su, Zhan
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Teo, Yik Ying
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Vukcevic, Damjan
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Donnelly, Peter
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Bentley, David
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Caulfield, Mark
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Craddock, Neil
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Farrall, Martin
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Hall, Alastair S.
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Hattersley, Andrew T.
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Matthew, Christopher G.
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McCarthy, Mark I.
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Parkes, Miles
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Pembrey, Marcus
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Samani, Nilesh J.
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Worthington, Jane
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Mitchell, Sarah L.
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Newby, Paul R.
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Carr-Smith, Jackie
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Pearce, Simon H. S.
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Gough, Stephen C. L.
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McGinnis, R
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Keniry, A.
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Deloukas, P.
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Reveille, John D.
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Zhou, Xiaodong
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Sims, Anne-Marie
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Dowling, Alison
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Taylor, Jacqueline
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Doan, Tracy
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Davis, John C.
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Savage, Laurie
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Ward, Michael M.
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Learch, Thomas L.
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Weisman, Michael H.
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Newport, Melanie
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Sirugo, Giorgio
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Lyons, Emily
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Vannberg, Fredrik
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Hill, Adrian V.S.
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Bradbury, Linda A.
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Farrar, Claire
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Pointon, Jennifer J.
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Wordsworth, Paul
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Franklyn, Jayne A.
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Heward, Joanne M.
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Simmonds, Matthew J.
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Gough, Stephen C.
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Seal, Sheila
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Stratton, Michael R.
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Rahman, Nazneen
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Ban, Maria
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Goris, An
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Sawcer, Stephen J.
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Compston, Alastair
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Conway, David
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Jallow, Muminatou
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Rockett, Kirk A.
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Kwiatkowski, Dominic P.
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Chaney, Amy
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Downes, Kate
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Ghori, Mohammed J.R.
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Gwilliam, Rhian
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Inouye, Michael
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Keniry, Andrew
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King, Emma
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McGinnis, Ralph
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Potter, Simon
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Ravindrarajah, Rathi
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Whittaker, Pamela
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Withers, David
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Stevens, Helen E.
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Walker, Neil M.
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Todd, John A.
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Easton, Doug
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Clayton, David G.
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Burton, Paul R.
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Tobin, Martin D.
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Barrett, Jeffrey C.
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Evans, David M.
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Morris, Andrew P.
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Cardon, Lon R.
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Cardin, Niall J.
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Davison, Dan
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Ferreira, Teresa
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Pereira-Gale, Joanne
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Hallgrimsdottir, Ingelief B.
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Howie, Bryan N.
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Marchini, Jonathan L.
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Spencer, Chris C.A.
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Su, Zhan
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Teo, Yik Ying
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Vukcevic, Damjan
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Donnelly, Peter
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Bentley, David
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Caulfield, Mark
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Craddock, Neil
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Farrall, Martin
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Hall, Alastair S.
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Hattersley, Andrew T.
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McCarthy, Mark I.
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Parkes, Miles
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Pembrey, Marcus
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Samani, Nilesh J.
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Worthington, Jane
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Carr-Smith, Jackie
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Pearce, Simon H. S.
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Gough, Stephen C. L.
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McGinnis, R
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Keniry, A.
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Deloukas, P.
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Reveille, John D.
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Zhou, Xiaodong
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Sims, Anne-Marie
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Dowling, Alison
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Doan, Tracy
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Davis, John C.
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Savage, Laurie
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Ward, Michael M.
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Learch, Thomas L.
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Weisman, Michael H.
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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., Seal, Sheila, Stratton, Michael R., Rahman, Nazneen, Ban, Maria, Goris, An, Sawcer, Stephen J., Compston, Alastair, Conway, David, Jallow, Muminatou, 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 S., 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 M., Morris, Andrew P., Cardon, Lon R., Cardin, Niall J., Davison, Dan, Ferreira, Teresa, Pereira-Gale, Joanne, Hallgrimsdottir, Ingelief B., Howie, Bryan N., Marchini, Jonathan L., Spencer, Chris C.A., Su, Zhan, Teo, Yik Ying, Vukcevic, Damjan, Donnelly, Peter, Bentley, David, Caulfield, Mark, Craddock, Neil, Farrall, Martin, Hall, Alastair S., Hattersley, Andrew T., Matthew, Christopher G., McCarthy, Mark I., Parkes, Miles, Pembrey, Marcus, Samani, Nilesh J., Worthington, Jane, Mitchell, Sarah L., Newby, Paul R., 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. (2007) Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nature Genetics, 39 (11), 1329-1337. (doi:10.1038/ng.2007.17). (PMID:17952073)

Record type: Article

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

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More information

Published date: November 2007
Keywords: confirmation, disease, single-nucleotide polymorphisms, susceptibility loci, children, population-structure, genetic association, risk, crohn-disease, project, blood, susceptibility, cancer, genome-wide association, ankylosing-spondylitis, graves-disease, association, aminopeptidase
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Identifiers

Local EPrints ID: 62522
URI: http://eprints.soton.ac.uk/id/eprint/62522
DOI: doi:10.1038/ng.2007.17
ISSN: 1061-4036
PURE UUID: 6bfcfad8-2f81-4532-b917-1a49b675353a

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Date deposited: 10 Feb 2009
Last modified: 15 Mar 2024 11:31

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Contributors

Author: Melanie Newport
Author: Giorgio Sirugo
Author: Emily Lyons
Author: Fredrik Vannberg
Author: Adrian V.S. Hill
Author: Linda A. Bradbury
Author: Claire Farrar
Author: Jennifer J. Pointon
Author: Paul Wordsworth
Author: Matthew A. Brown
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