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

Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., Ouwehand, W. H., Samani, N. J., Todd, J. A., Donnelly, P., Barrett, J. C., Davison, D., Easton, D., Evans, D. M., Leung, H. T., Marchini, J. L., Morris, A. P., Spencer, C. C. A., Tobin, M. D., Attwood, A. P., Boorman, J. P., Cant, B., Everson, U., Hussey, J. M., Jolley, J. D., Knight, A. S., Koch, K., Meech, E., Nutland, S., Prowse, C. V., 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., Breen, G., Clair, D. St, Caesar, S., Gordon-Smith, K., Jones, L., Fraser, C., Green, E. K., Grozeva, D., Hamshere, M. L., Holmans, P. A., Jones, I. R., Kirov, G., Moskivina, V., Nikolov, I., O'Donovan, M. C., Owen, M. J., Collier, D. A., Elkin, A., Farmer, A., Williamson, R., McGuffin, P., Young, A. H., Ferrier, I. N., Ball, S. G., Balmforth, A. J., Barrett, J. H., Bishop, T. D., Iles, M. M., Maqbool, A., Yuldasheva, N., Hall, A. S., Braund, P. S., Dixon, R. J., Mangino, M., Stevens, S., Thompson, J. R., Bredin, F., Tremelling, M., Parkes, M., Drummond, H., Lees, C. W., Nimmo, E. R., Satsangi, J., Fisher, S. A., Forbes, A., Lewis, C. M., Onnie, C. M., Prescott, N. J., Sanderson, J., Matthew, C. G., Barbour, J., Mohiuddin, M. K., Todhunter, C. E., Mansfield, J. C., Ahmad, T., Cummings, F. R., Jewell, D. P., Webster, J., Brown, M. J., Lathrop, M. G., Connell, J., Dominiczak, A., Marcano, C. A. B., Burke, B., Dobson, R., Gungadoo, J., Lee, K. L., Munroe, P. B., Newhouse, S. J., Onipinla, A., Wallace, C., Xue, M., Caulfield, M., Farrall, M., Barton, A., Bruce, I. N., Donovan, H., Eyre, S., Gilbert, P. D., Hilder, S. L., Hinks, A. M., John, S. L., Potter, C., Silman, A. J., Symmons, D. P. M., Thomson, W., Worthington, J., Dunger, D. B., Widmer, B., Frayling, T. M., 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., Hill, A. V. S., Bradbury, L. A., Farrar, C., Pointon, J. J., Wordsworth, P., Brown, Matthew A., Franklyn, J. A., 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., Conway, D., Jallow, M., Rockett, K. A., Bumpstead, S. J., Chaney, A., Downes, K., Ghori, M. J. R., Gwilliam, R., Hunt, S. E., Inouye, M., Keniry, A., King, E., McGinnis, R., Potter, S., Ravindrarajah, R., Whittaker, P., Widden, C., Withers, D., Cardin, N. J., Ferreira, T., Pereira-Gale, J., Hallgrimsdóttir, I. B., Howie, B. N., Su, Z., Teo, Y. Y., Vukcevic, D., Bentley, D., Mitchell, S. L., Newby, P. R., Brand, O. J., Carr-Smith, J., Pearce, S. H. S., Gough, S. C. L., McGinnis, R., Keniry, A., Deloukas, P., Reveille, J. D., Zhou, X., Sims, A. M., Dowling, A., Taylor, J., Doan, T., Davis, J. C., Savage, L., Ward, M. M., Learch, T. L., & Weisman, M. H. (2007) Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nature Genetics, 39(11), pp. 1329-1337.

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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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ID Code: 89475
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :716
Export Date: 21 September 2015
CODEN: NGENE
Correspondence Address: Cardon, L.R.; Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom; email: lcardon@fhcrc.org
Keywords: adult, ankylosing spondylitis, article, ARTS1 gene, autoimmunity, breast cancer, controlled study, data analysis, female, gene, gene locus, gene replication, genetic association, genetic susceptibility, genetic variability, genotype, human, IL23R gene, immunoregulation, major clinical study, major histocompatibility complex, male, multiple sclerosis, North America, priority journal, single nucleotide polymorphism, thyroid disease, Aminopeptidases, Breast Neoplasms, Case-Control Studies, Chromosome Mapping, Genetics, Population, Haplotypes, Humans, Linkage Disequilibrium, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Receptors, Immunologic, Receptors, Interleukin, Spondylitis, Ankylosing, Thyroiditis, Autoimmune
DOI: 10.1038/ng.2007.17
ISSN: 1061-4036
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: © 2007 Nature Publishing Group
Deposited On: 26 Oct 2015 00:02
Last Modified: 19 Aug 2016 02:36

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