High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

de Bakker, Paul I. W.; Ärlsetig, Lisbeth; De Bakker, P. I. W.; Moitra, R. K.; Prouse, P. J.; Shawe, D. J.; Crisp, A. J.; Gaston, J. S. H.; Hall, F. C.; Hazleman, B. L.; Amos, Christopher I.; Eyre, Steve; Jenner,; Lillicrap,; Ostor, A.; Silverman, B.; Speed, C.; Bruce, I. N.; Hyrich, K.; Ho, P.; Gorodkin, R.; Martin, Paul; Armstrong, D.; Toes, Rene E. M.; Chuck, A. J.; Bowes, John; Hailwood, S.; Kumar, N.; Badcock, L. J.; Deighton, C. M.; Huizinga, Tom W. J.; O'Reilly, S. C.; Raj, N.; Regan, M. R.; Summers, G. D.; Williams, R. A.; Lambert,; Stevens, R.; Diogo, Dorothée; Wilkinson, C.; Hamilton, J.; Heycock, C. R.; Kelly, C. A.; Saravanan,; Rees, D. H.; Williams, R. B.; Bingham, S.; Emery, P.; Morgan, A.; Bird, H. A.; Conaghan, P. G.; Westra, Harm-Jan; Pease, C. T.; Wakefield, R. J.; Lee, Annette; Chalam, S.; Mulherin, D.; Price, T.; Sheeran, T.; Venkatachalam, S.; Gaffney, K.; Macgregor, A. J.; Marshall, T.; Merry, P.; Scott, D. G. I.; Birrell, F. N.; Crook, P. R.; Harrison, B.; Pattrick, M.; Snowden, H. N.; Barton, Anne; Bowden, A. P.; Smith, E. E.; Klimiuk, P.; Speden, D. J.; Sheehan, N. J.; Wijmenga, Cisca; Williams, N. E.; Dahiya, S.; Hull, R. G.; Ledingham, J. M.; Mccrae, F.; Shaban, M. R.; Khor, Chiea Chuen; Trynka, Gosia; Thomas, A. L.; Young Min, S. A.; Bamji, A. N.; Cheung, N. T.; Buckley, C. D.; Heng, Khai Koon; Carruthers, D. C.; Franke, Lude; Elamanchi, R.; Gordon, P. C.; Grindulis, K. A.; Khattak, F.; Raza, K.; Situnayake, D.; Till, S.; Akil, M.; Tattersall, R.; Zhernakova, Alexandra; Kilding, R.; Dunley, L.; Boulton, J.; Alfredsson, Lars; Tait, T.; Hunt, Sarah E.; Wilson, A. G.; Bax, D. E.; Clarke, F.; Fordham, J. N.; Plant, M. J.; Hu, Xinli; Tuck,; Pathare, S. K.; Stahl, Eli; Edwards, C. J.; Arden, N. K.; Symmons, Deborah; Armstrong, R. D.; Calogeras, A.; Sandor, Cynthia; Cooper, C.; Davidson, B. K. S.; Dennison, E. M.; Abernethy, V. E.; Clewes, A. R.; Dawson, J. K.; Lynch, M.; Kitas, G.; Delamere, J. P.; Viatte, Sebastien; Erb, N.; Klocke, R.; Whallett, A. J.; Davila, Sonia; Rich, Stephen S.; Crook, P.; Foster, H. E.; Griffiths, B.; Griffiths, I. D.; Grove, M. L.; Isaacs,; Kay, L.; Ng, W. F.; Myers, A.; Platt, P. N.; Hj, Westra; Gonzalez-Gay, Miguel A.; McAllister, Kate; Walker, D. J.; Bowman,; Jobanputra, P.; Martin, P.; Jubb, R. W.; Rankin, E. C.; Dawes, P. T.; Dowson, C. M.; Andrews, Robert; Hassell, A.; Hay, E. M.; Kamath, S.; Packham, J.; Sandhu, R. S.; Shadforth,; Edkins, Sarah; Bukhari, M.; Dodds, W. N.; Halsey, J. P.; Mitchell, W. S.; O'Reilly, D. T.; Donnelly, S. P.; Doyle, D.; Hakim, A.; Lanham, J. G.; Tahir, H. I. S.; Rathi, J.; Rai, A.; Langford, Cordelia; Rowe, I. F.; Prabu, A.; Buckley, C. A. M.; Plenge, Robert M.; Padyukov, Leonid; Pi, de Bakker; Burton, P. R.; Ci, Amos; Clayton, D. G.; Cardon, L. R.; Craddock, N.; Duncanson, A.; Kwiatkowski, D. P.; McCarthy, M. I.; Ouwehand, W. H.; Samani, N. J.; Concannon, Pat; Todd, J. A.; Donnelly, P.; Barrett, J. C.; Davison, D.; Easton, D.; Gregersen, Peter K.; Cc, Khor; Evans, D.; Onengut-Gumuscu, Suna; Leung, H.-T.; Marchini, J. L.; Morris, A. P.; Spencer, C. C. A.; Tobin,; Attwood, A. P.; Boorman, J. P.; Kk, Heng; Cant, B.; Everson, U.; Hussey, J. M.; Jolley,; Knight, A. S.; Koch, K.; Deloukas, Panos; Meech, E.; Nutland, S.; Re, Toes; Prowse, C.; Stevens, H. E.; Taylor, N. C.; Walters, G. R.; Walker, N. M.; Watkins, N. A.; Winzer, T.; Jones, R. W.; McArdle, W. L.; Ring, S. M.; Strachan, D. P.; Pembrey, M.; Rodriguez-Rodriguez, Luis; Breen, G.; St Clair, D.; Caesar, S.; Gordon-Smith, K.; Jones, L.; Tw, Huizinga; Fraser, C.; Se, Hunt; Green, E. K.; Grozeva, D.; Hamshere, M. L.; Holmans, P. A.; Jones, I. R.; Kirov, G.; Moskvina,; Nikolov, I.; O'Donovan, M. C.; Owen, M. J.; Collier, D. A.; Martin, Javier; Elkin, A.; Farmer, A.; Williamson, R.; McGuffin, P.; Young, A. H.; Nicol Ferrier, I.; Ball, S. G.; Rantapää-Dahlqvist, Solbritt; Balmforth, A. J.; Barrett, J. H.; Timothy Bishop, D.; Iles, M. M.; Maqbool, A.; Yuldasheva, N.; Hall, A. S.; Braund, P. S.; Dixon, R. J.; Mangino, M.; Stevens, S.; Thompson,; Bredin, F.; Tremelling, M.; Parkes, M.; Raychaudhuri, Soumya; Drummond, H.; Lees, C. W.; Nimmo, E. R.; Satsangi, J.; Fisher, S. A.; Forbes, A.; Lewis, C. M.; Klareskog, Lars; Onnie, C. M.; Prescott, N. J.; Sanderson, J.; Ss, Rich; Mathew, C. G.; Barbour, J.; Khalid Mohiuddin, M.; Symmons, D. P. M.; Todhunter, C. E.; Mansfield, J. C.; Ahmad, T.; Cummings, F. R.; Jewell, D. P.; Webster, J.; Brown, M. J.; Mark Lathrop, G.; Dominiczak, A.; Braga Marcano, C. A.; Burke, B.; Dobson, R.; Gungadoo, J.; Lee, K. L.; Munroe, P. B.; Ma, Gonzalez Gay; Newhouse, S. J.; Onipinla, A.; Wallace, C.; Xue, M.; Caulfield, M.; Farrall, M.; Donovan, H.; Gilbert, P. D.; Hider, S. L.; Hinks, A. M.; John, S. L.; Potter, C.; Silman, A. J.; Thomson, W.; Dunger, D. B.; Widmer, B.; Frayling, T. M.; Arlsetig, Lisbeth; Freathy, R. M.; Lango, H.; Perry, J. R. B.; Shields, B. M.; Weedon, M. N.; Hattersley, A. T.; Hitman, G. A.; Walker, M.; Elliott, K. S.; Groves, C. J.; Lindgren, C. M.; Rayner, N. W.; Timpson, N. J.; Zeggini, E.; Newport, M.; Sirugo, G.; Lyons, E.; Vannberg, F.; Worthington, Jane; Hill, A. V. S.; Bradbury, L. A.; Pointon, J. J.; Wordsworth, P.; Brown,; Franklyn, J. A.; Rm, Plenge; Heward, J. M.; Simmonds, M. J.; Gough, S. C. L.; Seal, S.; Stratton, M. R.; Rahman, N.; Ban, M.; Goris, A.; Sawcer, S. J.; Compston, A.; Jallow, M.; Rockett, K. A.; Bumpstead, S. J.; Chaney, A.; Downes, K.; Ghori, M.; Gwilliam, R.; Inouye, M.; Keniry, A.; King, E.; McGinnis, R.; Potter, S.; Ravindrarajah, R.; Whittaker, P.; Widden, C.; Withers, D.; Pk, Gregersen; Cardin, N. J.; Ferreira, T.; Pereira-Gale, J.; Hallgrimsdóttir, I. B.; Howie, B. N.; Su, Z.; Ying Teo, Y.; Vukcevic, D.; Bentley, D.

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Stephen Eyre
de Bakker et al., 2012

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Nature Research, Nature Genetics, 12(44), p. 1336-1340, 2012

DOI: 10.1038/ng.2462

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@article{de Bakker2012,
  abstract = {Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.},
  author = {de Bakker, Paul I. W. and Ärlsetig, Lisbeth and De Bakker, P. I. W. and Moitra, R. K. and Prouse, P. J. and Shawe, D. J. and Crisp, A. J. and Gaston, J. S. H. and Hall, F. C. and Hazleman, B. L. and Amos, Christopher I. and Eyre, Steve and Jenner,  and Lillicrap,  and Ostor, A. and Silverman, B. and Speed, C. and Bruce, I. N. and Hyrich, K. and Ho, P. and Gorodkin, R. and Martin, Paul and Armstrong, D. and Toes, Rene E. M. and Chuck, A. J. and Bowes, John and Hailwood, S. and Kumar, N. and Badcock, L. J. and Deighton, C. M. and Huizinga, Tom W. J. and O'Reilly, S. C. and Raj, N. and Regan, M. R. and Summers, G. D. and Williams, R. A. and Lambert,  and Stevens, R. and Diogo, Dorothée and Wilkinson, C. and Hamilton, J. and Heycock, C. R. and Kelly, C. A. and Saravanan,  and Rees, D. H. and Williams, R. B. and Bingham, S. and Emery, P. and Morgan, A. and Bird, H. A. and Conaghan, P. G. and Westra, Harm-Jan and Pease, C. T. and Wakefield, R. J. and Lee, Annette and Chalam, S. and Mulherin, D. and Price, T. and Sheeran, T. and Venkatachalam, S. and Gaffney, K. and Macgregor, A. J. and Marshall, T. and Merry, P. and Scott, D. G. I. and Birrell, F. N. and Crook, P. R. and Harrison, B. and Pattrick, M. and Snowden, H. N. and Barton, Anne and Bowden, A. P. and Smith, E. E. and Klimiuk, P. and Speden, D. J. and Sheehan, N. J. and Wijmenga, Cisca and Williams, N. E. and Dahiya, S. and Hull, R. G. and Ledingham, J. M. and Mccrae, F. and Shaban, M. R. and Khor, Chiea Chuen and Trynka, Gosia and Thomas, A. L. and Young Min, S. A. and Bamji, A. N. and Cheung, N. T. and Buckley, C. D. and Heng, Khai Koon and Carruthers, D. C. and Franke, Lude and Elamanchi, R. and Gordon, P. C. and Grindulis, K. A. and Khattak, F. and Raza, K. and Situnayake, D. and Till, S. and Akil, M. and Tattersall, R. and Zhernakova, Alexandra and Kilding, R. and Dunley, L. and Boulton, J. and Alfredsson, Lars and Tait, T. and Hunt, Sarah E. and Wilson, A. G. and Bax, D. E. and Clarke, F. and Fordham, J. N. and Plant, M. J. and Hu, Xinli and Tuck,  and Pathare, S. K. and Stahl, Eli and Edwards, C. J. and Arden, N. K. and Symmons, Deborah and Armstrong, R. D. and Calogeras, A. and Sandor, Cynthia and Cooper, C. and Davidson, B. K. S. and Dennison, E. M. and Abernethy, V. E. and Clewes, A. R. and Dawson, J. K. and Lynch, M. and Kitas, G. and Delamere, J. P. and Viatte, Sebastien and Erb, N. and Klocke, R. and Whallett, A. J. and Davila, Sonia and Rich, Stephen S. and Crook, P. and Foster, H. E. and Griffiths, B. and Griffiths, I. D. and Grove, M. L. and Isaacs,  and Kay, L. and Ng, W. F. and Myers, A. and Platt, P. N. and Hj, Westra and Gonzalez-Gay, Miguel A. and McAllister, Kate and Walker, D. J. and Bowman,  and Jobanputra, P. and Martin, P. and Jubb, R. W. and Rankin, E. C. and Dawes, P. T. and Dowson, C. M. and Andrews, Robert and Hassell, A. and Hay, E. M. and Kamath, S. and Packham, J. and Sandhu, R. S. and Shadforth,  and Edkins, Sarah and Bukhari, M. and Dodds, W. N. and Halsey, J. P. and Mitchell, W. S. and O'Reilly, D. T. and Donnelly, S. P. and Doyle, D. and Hakim, A. and Lanham, J. G. and Tahir, H. I. S. and Rathi, J. and Rai, A. and Langford, Cordelia and Rowe, I. F. and Prabu, A. and Buckley, C. A. M. and Plenge, Robert M. and Padyukov, Leonid and Pi, de Bakker and Burton, P. R. and Ci, Amos and Clayton, D. G. and Cardon, L. R. and Craddock, N. and Duncanson, A. and Kwiatkowski, D. P. and McCarthy, M. I. and Ouwehand, W. H. and Samani, N. J. and Concannon, Pat and Todd, J. A. and Donnelly, P. and Barrett, J. C. and Davison, D. and Easton, D. and Gregersen, Peter K. and Cc, Khor and Evans, D. and Onengut-Gumuscu, Suna and Leung, H.-T. and Marchini, J. L. and Morris, A. P. and Spencer, C. C. A. and Tobin,  and Attwood, A. P. and Boorman, J. P. and Kk, Heng and Cant, B. and Everson, U. and Hussey, J. M. and Jolley,  and Knight, A. S. and Koch, K. and Deloukas, Panos and Meech, E. and Nutland, S. and Re, Toes and Prowse, C. and Stevens, H. E. and Taylor, N. C. and Walters, G. R. and Walker, N. M. and Watkins, N. A. and Winzer, T. and Jones, R. W. and McArdle, W. L. and Ring, S. M. and Strachan, D. P. and Pembrey, M. and Rodriguez-Rodriguez, Luis and Breen, G. and St Clair, D. and Caesar, S. and Gordon-Smith, K. and Jones, L. and Tw, Huizinga and Fraser, C. and Se, Hunt and Green, E. K. and Grozeva, D. and Hamshere, M. L. and Holmans, P. A. and Jones, I. R. and Kirov, G. and Moskvina,  and Nikolov, I. and O'Donovan, M. C. and Owen, M. J. and Collier, D. A. and Martin, Javier and Elkin, A. and Farmer, A. and Williamson, R. and McGuffin, P. and Young, A. H. and Nicol Ferrier, I. and Ball, S. G. and Rantapää-Dahlqvist, Solbritt and Balmforth, A. J. and Barrett, J. H. and Timothy Bishop, D. and Iles, M. M. and Maqbool, A. and Yuldasheva, N. and Hall, A. S. and Braund, P. S. and Dixon, R. J. and Mangino, M. and Stevens, S. and Thompson,  and Bredin, F. and Tremelling, M. and Parkes, M. and Raychaudhuri, Soumya and Drummond, H. and Lees, C. W. and Nimmo, E. R. and Satsangi, J. and Fisher, S. A. and Forbes, A. and Lewis, C. M. and Klareskog, Lars and Onnie, C. M. and Prescott, N. J. and Sanderson, J. and Ss, Rich and Mathew, C. G. and Barbour, J. and Khalid Mohiuddin, M. and Symmons, D. P. M. and Todhunter, C. E. and Mansfield, J. C. and Ahmad, T. and Cummings, F. R. and Jewell, D. P. and Webster, J. and Brown, M. J. and Mark Lathrop, G. and Dominiczak, A. and Braga Marcano, C. A. and Burke, B. and Dobson, R. and Gungadoo, J. and Lee, K. L. and Munroe, P. B. and Ma, Gonzalez Gay and Newhouse, S. J. and Onipinla, A. and Wallace, C. and Xue, M. and Caulfield, M. and Farrall, M. and Donovan, H. and Gilbert, P. D. and Hider, S. L. and Hinks, A. M. and John, S. L. and Potter, C. and Silman, A. J. and Thomson, W. and Dunger, D. B. and Widmer, B. and Frayling, T. M. and Arlsetig, Lisbeth and Freathy, R. M. and Lango, H. and Perry, J. R. B. and Shields, B. M. and Weedon, M. N. and Hattersley, A. T. and Hitman, G. A. and Walker, M. and Elliott, K. S. and Groves, C. J. and Lindgren, C. M. and Rayner, N. W. and Timpson, N. J. and Zeggini, E. and Newport, M. and Sirugo, G. and Lyons, E. and Vannberg, F. and Worthington, Jane and Hill, A. V. S. and Bradbury, L. A. and Pointon, J. J. and Wordsworth, P. and Brown,  and Franklyn, J. A. and Rm, Plenge and Heward, J. M. and Simmonds, M. J. and Gough, S. C. L. and Seal, S. and Stratton, M. R. and Rahman, N. and Ban, M. and Goris, A. and Sawcer, S. J. and Compston, A. and Jallow, M. and Rockett, K. A. and Bumpstead, S. J. and Chaney, A. and Downes, K. and Ghori, M. and Gwilliam, R. and Inouye, M. and Keniry, A. and King, E. and McGinnis, R. and Potter, S. and Ravindrarajah, R. and Whittaker, P. and Widden, C. and Withers, D. and Pk, Gregersen and Cardin, N. J. and Ferreira, T. and Pereira-Gale, J. and Hallgrimsdóttir, I. B. and Howie, B. N. and Su, Z. and Ying Teo, Y. and Vukcevic, D. and Bentley, D.},
  doi = {10.1038/ng.2462},
  journal = {Nature Genetics},
  month = {nov},
  pages = {1336-1340},
  title = {High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis},
  url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605761},
  volume = {44},
  year = {2012}
}

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High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

Journal article published in 2012 by Paul I. W. de Bakker, Lisbeth Ärlsetig, P. I. W. De Bakker, R. K. Moitra, P. J. Prouse, D. J. Shawe, A. J. Crisp, J. S. H. Gaston, F. C. Hall, B. L. Hazleman, Christopher I. Amos, Steve Eyre

, Jenner, Lillicrap, A. Ostor and other authors. Paul I. W. de Bakker, Lisbeth Ärlsetig, P. I. W. De Bakker, R. K. Moitra, P. J. Prouse, D. J. Shawe, A. J. Crisp, J. S. H. Gaston, F. C. Hall, B. L. Hazleman, Christopher I. Amos, Steve Eyre

, Jenner, Lillicrap, A. Ostor, B. Silverman, C. Speed, I. N. Bruce, K. Hyrich, P. Ho, R. Gorodkin, Paul Martin

, D. Armstrong, Rene E. M. Toes, A. J. Chuck, John Bowes, S. Hailwood, N. Kumar, L. J. Badcock, C. M. Deighton, Tom W. J. Huizinga, S. C. O'Reilly, N. Raj, M. R. Regan, G. D. Summers, R. A. Williams, Lambert, R. Stevens, Dorothée Diogo, C. Wilkinson, J. Hamilton, C. R. Heycock, C. A. Kelly, Saravanan, D. H. Rees, R. B. Williams, S. Bingham, P. Emery, A. Morgan, H. A. Bird, P. G. Conaghan, Harm-Jan Westra, C. T. Pease, R. J. Wakefield, Annette Lee, S. Chalam, D. Mulherin, T. Price, T. Sheeran, S. Venkatachalam, K. Gaffney, A. J. Macgregor, T. Marshall, P. Merry, D. G. I. Scott, F. N. Birrell, P. R. Crook, B. Harrison, M. Pattrick, H. N. Snowden, Anne Barton

, A. P. Bowden, E. E. Smith, P. Klimiuk, D. J. Speden, N. J. Sheehan, Cisca Wijmenga

, N. E. Williams, S. Dahiya, R. G. Hull, J. M. Ledingham, F. Mccrae, M. R. Shaban, Chiea Chuen Khor, Gosia Trynka, A. L. Thomas, S. A. Young Min, A. N. Bamji, N. T. Cheung, C. D. Buckley, Khai Koon Heng, D. C. Carruthers, Lude Franke

, R. Elamanchi, P. C. Gordon, K. A. Grindulis, F. Khattak, K. Raza, D. Situnayake, S. Till, M. Akil, R. Tattersall, Alexandra Zhernakova, R. Kilding, L. Dunley, J. Boulton, Lars Alfredsson, T. Tait, Sarah E. Hunt, A. G. Wilson, D. E. Bax, F. Clarke, J. N. Fordham, M. J. Plant, Xinli Hu, Tuck, S. K. Pathare, Eli Stahl, C. J. Edwards, N. K. Arden, Deborah Symmons, R. D. Armstrong, A. Calogeras, Cynthia Sandor, C. Cooper, B. K. S. Davidson, E. M. Dennison, V. E. Abernethy, A. R. Clewes, J. K. Dawson, M. Lynch, G. Kitas, J. P. Delamere, Sebastien Viatte, N. Erb, R. Klocke, A. J. Whallett, Sonia Davila, Stephen S. Rich, P. Crook, H. E. Foster, B. Griffiths, I. D. Griffiths, M. L. Grove, Isaacs, L. Kay, W. F. Ng, A. Myers, P. N. Platt, Westra Hj, Miguel A. Gonzalez-Gay, Kate McAllister, D. J. Walker, Bowman, P. Jobanputra, P. Martin, R. W. Jubb, E. C. Rankin, P. T. Dawes, C. M. Dowson, Robert Andrews, A. Hassell, E. M. Hay, S. Kamath, J. Packham, R. S. Sandhu, Shadforth, Sarah Edkins, M. Bukhari, W. N. Dodds, J. P. Halsey, W. S. Mitchell, D. T. O'Reilly, S. P. Donnelly, D. Doyle, A. Hakim, J. G. Lanham, H. I. S. Tahir, J. Rathi, A. Rai, Cordelia Langford, I. F. Rowe, A. Prabu, C. A. M. Buckley, Robert M. Plenge, Leonid Padyukov

, de Bakker Pi, P. R. Burton, Amos Ci, D. G. Clayton, L. R. Cardon, N. Craddock, A. Duncanson, D. P. Kwiatkowski, M. I. McCarthy, W. H. Ouwehand, N. J. Samani, Pat Concannon, J. A. Todd, P. Donnelly, J. C. Barrett, D. Davison, D. Easton, Peter K. Gregersen, Khor Cc, D. Evans, Suna Onengut-Gumuscu, H.-T. Leung, J. L. Marchini, A. P. Morris, C. C. A. Spencer, Tobin, A. P. Attwood, J. P. Boorman, Heng Kk, B. Cant, U. Everson, J. M. Hussey, Jolley, A. S. Knight, K. Koch, Panos Deloukas

, E. Meech, S. Nutland, Toes Re, C. Prowse, H. E. Stevens, N. C. Taylor, G. R. Walters, N. M. Walker, N. A. Watkins, T. Winzer, R. W. Jones, W. L. McArdle, S. M. Ring, D. P. Strachan, M. Pembrey, Luis Rodriguez-Rodriguez, G. Breen, D. St Clair, S. Caesar, K. Gordon-Smith, L. Jones, Huizinga Tw, C. Fraser, Hunt Se, E. K. Green, D. Grozeva, M. L. Hamshere, P. A. Holmans, I. R. Jones, G. Kirov, Moskvina, I. Nikolov, M. C. O'Donovan, M. J. Owen, D. A. Collier, Javier Martin, A. Elkin, A. Farmer, R. Williamson, P. McGuffin, A. H. Young, I. Nicol Ferrier, S. G. Ball, Solbritt Rantapää-Dahlqvist, A. J. Balmforth, J. H. Barrett, D. Timothy Bishop, M. M. Iles, A. Maqbool, N. Yuldasheva, A. S. Hall, P. S. Braund, R. J. Dixon, M. Mangino, S. Stevens, Thompson, F. Bredin, M. Tremelling, M. Parkes, Soumya Raychaudhuri, H. Drummond, C. W. Lees, E. R. Nimmo, J. Satsangi, S. A. Fisher, A. Forbes, C. M. Lewis, Lars Klareskog, C. M. Onnie, N. J. Prescott

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Abstract

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

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High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

Abstract