Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

Autoria(s): Tsoi, L. C.; Spain, S. L.; Knight, J.; Ellinghaus, E.; Stuart, P. E.; Capon, F.; Ding, J.; Li, Y.; Tejasvi, T.; Gudjonsson, J. E.; Kang, H. M.; Allen, M. H.; McManus, R.; Novelli, G.; Samuelsson, L.; Schalkwijk, J.; Ståhle, M.; Burden, A. D.; Smith, C. H.; Cork, M. J.; Estivill, X.; Bowcock, A. M.; Krueger, G. G.; Weger, W.; Worthington, J.; Tazi-Ahnini, R.; Nestle, F. O.; Hayday, A.; Hoffmann, P.; Winkelmann, J.; Wijmenga, C.; Langford, C.; Edkins, S.; Andrews, R.; Blackburn, H.; Strange, A.; Band, G.; Pearson, R. D.; Vukcevic, D.; Spencer, C. C. A.; Deloukas, P.; Mrowietz, U.; Schreiber, S.; Weidinger, S.; Koks, S.; Kingo, K.; Esko, T.; Metspalu, A.; Lim, H. W.; Voorhees, J. J.; Weichenthal, M.; Wichmann, H. E.; Chandran, V.; Rosen, C. F.; Rahman, P.; Gladman, D. D.; Griffiths, C. E. M.; Reis, A.; Kere, J.; Nnair, R. P.; Franke, A.; Barker, J. N.; Abecasis, G. R.; Eelder, J. T.; Ttrembath, R.; Duffin, K. C.; Helms, C.; Goldgar, D.; Li, Y.; Paschall, J.; Malloy, M. J.; Pullinger, C. R.; Kane, J. P.; Gardner, J.; Perlmutter, A.; Miner, A.; Feng, B. J.; Hiremagalore, R.; Ike, R. W.; Christophers, E.; Henseler, T.; Ruether, A.; Schrodi, S. J.; Prahalad, S.; Guthery, S. L.; Fischer, J.; Liao, W.; Kwok, P.; Menter, A.; Lathrop, G. M.; Wise, C.; Begovich, A. B.; Onoufriadis, A.; Weale, M. E.; Hofer, A.; Salmhofer, W.; Wolf, P.; Kainu, K.; Saarialho-Kere, U.; Suomela, S.; Badorf, P.; Hüffmeier, U.; Kurrat, W.; Küster, W.; Lascorz, J.; Mössner, R.; Schürmeier-Horst, F.; Ständer, M.; Traupe, H.; Bergboer, J. G. M.; Heijer, M. D.; Van De Kerkhof, P. C.; Zeeuwen, P. L. J. M.; Barnes, L.; Campbell, L. E.; Cusack, C.; Coleman, C.; Conroy, J.; Ennis, S.; Fitzgerald, O.; Gallagher, P.; Irvine, A. D.; Kirby, B.; Markham, T.; McLean, W. H. I.; McPartlin, J.; Rogers, S. F.; Ryan, A. W.; Zawirska, A.; Giardina, E.; Lepre, T.; Perricone, C.; Martín-Ezquerra, G.; Pujol, R. M.; Riveira-Munoz, E.; Inerot, A.; Naluai, Å T.; Mallbris, L.; Wolk, K.; Leman, J.; Barton, A.; Warren, R. B.; Young, H. S.; Ricano-Ponce, I.; Trynka, G.; Pellett, F. J.; Henschel, A.; Aurand, M.; Bebo, B.; Gieger, C.; Illig, T.; Moebus, S.; Jöckel, K. H.; Erbel, R.; Donnelly, P.; Peltonen, L.; Blackwell, J. M.; Bramon, E.; Brown, M. A.; Casas, J. P.; Corvin, A.; Craddock, N.; Duncanson, A.; Jankowski, J.; Markus, H. S.; Mathew, C. G.; McCarthy, M. I.; Palmer, C. N. A.; Plomin, R.; Rautanen, A.; Sawcer, S. J.; Samani, N.; Viswanathan, A. C.; Wood, N. W.; Bellenguez, C.; Freeman, C.; Hellenthal, G.; Giannoulatou, E.; Pirinen, M.; Su, Z.; Hunt, S. E.; Gwilliam, R.; Bumpstead, S. J.; Dronov, S.; Gillman, M.; Gray, E.; Hammond, N.; Jayakumar, A.; McCann, O. T.; Liddle, J.; Perez, M. L.; Potter, S. C.; Ravindrarajah, R.; Ricketts, M.; Waller, M.; Weston, P.; Widaa, S.; Whittaker, P.; Neir, R. P.; Barker, J. N. W. N.; Abecasis, G. R.; Elder, J. T.; Trembath, R. C.
Data(s)

2012
Resumo

To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense. © 2012 Nature America, Inc. All rights reserved.
Identificador

http://eprints.qut.edu.au/89326/
Publicador

Nature Publishing Group
Relação

DOI:10.1038/ng.2467

Tsoi, L. C., Spain, S. L., Knight, J., Ellinghaus, E., Stuart, P. E., Capon, F., Ding, J., Li, Y., Tejasvi, T., Gudjonsson, J. E., Kang, H. M., Allen, M. H., McManus, R., Novelli, G., Samuelsson, L., Schalkwijk, J., Ståhle, M., Burden, A. D., Smith, C. H., Cork, M. J., Estivill, X., Bowcock, A. M., Krueger, G. G., Weger, W., Worthington, J., Tazi-Ahnini, R., Nestle, F. O., Hayday, A., Hoffmann, P., Winkelmann, J., Wijmenga, C., Langford, C., Edkins, S., Andrews, R., Blackburn, H., Strange, A., Band, G., Pearson, R. D., Vukcevic, D., Spencer, C. C. A., Deloukas, P., Mrowietz, U., Schreiber, S., Weidinger, S., Koks, S., Kingo, K., Esko, T., Metspalu, A., Lim, H. W., Voorhees, J. J., Weichenthal, M., Wichmann, H. E., Chandran, V., Rosen, C. F., Rahman, P., Gladman, D. D., Griffiths, C. E. M., Reis, A., Kere, J., Nnair, R. P., Franke, A., Barker, J. N., Abecasis, G. R., Eelder, J. T., Ttrembath, R., Duffin, K. C., Helms, C., Goldgar, D., Li, Y., Paschall, J., Malloy, M. J., Pullinger, C. R., Kane, J. P., Gardner, J., Perlmutter, A., Miner, A., Feng, B. J., Hiremagalore, R., Ike, R. W., Christophers, E., Henseler, T., Ruether, A., Schrodi, S. J., Prahalad, S., Guthery, S. L., Fischer, J., Liao, W., Kwok, P., Menter, A., Lathrop, G. M., Wise, C., Begovich, A. B., Onoufriadis, A., Weale, M. E., Hofer, A., Salmhofer, W., Wolf, P., Kainu, K., Saarialho-Kere, U., Suomela, S., Badorf, P., Hüffmeier, U., Kurrat, W., Küster, W., Lascorz, J., Mössner, R., Schürmeier-Horst, F., Ständer, M., Traupe, H., Bergboer, J. G. M., Heijer, M. D., Van De Kerkhof, P. C., Zeeuwen, P. L. J. M., Barnes, L., Campbell, L. E., Cusack, C., Coleman, C., Conroy, J., Ennis, S., Fitzgerald, O., Gallagher, P., Irvine, A. D., Kirby, B., Markham, T., McLean, W. H. I., McPartlin, J., Rogers, S. F., Ryan, A. W., Zawirska, A., Giardina, E., Lepre, T., Perricone, C., Martín-Ezquerra, G., Pujol, R. M., Riveira-Munoz, E., Inerot, A., Naluai, Å T., Mallbris, L., Wolk, K., Leman, J., Barton, A., Warren, R. B., Young, H. S., Ricano-Ponce, I., Trynka, G., Pellett, F. J., Henschel, A., Aurand, M., Bebo, B., Gieger, C., Illig, T., Moebus, S., Jöckel, K. H., Erbel, R., Donnelly, P., Peltonen, L., Blackwell, J. M., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Craddock, N., Duncanson, A., Jankowski, J., Markus, H. S., Mathew, C. G., McCarthy, M. I., Palmer, C. N. A., Plomin, R., Rautanen, A., Sawcer, S. J., Samani, N., Viswanathan, A. C., Wood, N. W., Bellenguez, C., Freeman, C., Hellenthal, G., Giannoulatou, E., Pirinen, M., Su, Z., Hunt, S. E., Gwilliam, R., Bumpstead, S. J., Dronov, S., Gillman, M., Gray, E., Hammond, N., Jayakumar, A., McCann, O. T., Liddle, J., Perez, M. L., Potter, S. C., Ravindrarajah, R., Ricketts, M., Waller, M., Weston, P., Widaa, S., Whittaker, P., Neir, R. P., Barker, J. N. W. N., Abecasis, G. R., Elder, J. T., & Trembath, R. C. (2012) Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nature Genetics, 44(12), pp. 1341-1348.
Direitos

Copyright Nature America
Fonte

Faculty of Health; Institute of Health and Biomedical Innovation
Palavras-Chave #caspase recruitment domain signaling protein #DNA directed DNA polymerase beta #immunoglobulin enhancer binding protein #methyl CpG binding protein 2 #retinoic acid inducible protein I #STAT3 protein #transcription factor RUNX3 #article #controlled study #Europe #gene identification #gene locus #genetic association #genetic susceptibility #genotype #host resistance #human #human cell #innate immunity #macrophage activation #major clinical study #priority journal #psoriasis #CARD Signaling Adaptor Proteins #Core Binding Factor Alpha 3 Subunit #DEAD-box RNA Helicases #European Continental Ancestry Group #Genetic Loci #Genetic Predisposition to Disease #Genome-Wide Association Study #GTPase-Activating Proteins #Guanylate Cyclase #Humans #Immunity #Innate #Membrane Proteins #Oligonucleotide Array Sequence Analysis #Polymorphism #Single Nucleotide #Skin #STAT3 Transcription Factor #T-Lymphocytes
Tipo

Journal Article
Acesso ao item digital