Genetics of Ankylosing Spondylitis Study (GASS)

Ankylosing Spondylitis: Not simply back pain

Ankylosing Spondylitis (AS) is a relatively common inflammatory disease, mainly involving the joints of the pelvis and spine, which affects approximately 3 in 1000 people.  Inflammation causes erosions in the sacroiliac joints and vertebrae, with new bone formation that can lead to fusion of the joints.  It has been known for a long time that AS is heritable (can ‘run’ in families) and studies have shown that there is a strong genetic or inherited element.

Genes or DNA carry the information that determines many characteristics of a person, including the features like hair or eye colour, but also things like disease susceptibility. RNA is produced from genes and is used like a set of instructions to produce all the proteins found in the body.  Since the early 1970’s a gene, HLA-B27, has been known to be present in about 80-90% of people with AS, although only 1-5% of HLA-B27 positive individuals will develop AS.  This means there is likely a lot of other genes involved too.

Our group is working to identify the genes involved in the development of AS, and are the main centre world-wide for this sort of research.  We have now identified over 100 other genes which are also involved in the disease, but there are clearly hundreds more to go.

These genetic findings have made a big difference in the treatment of this disease already, with a new class of drugs (targeting the inflammatory proteins IL-23 and IL-17) coming into AS treatment regimes because of our genetic discoveries. A sample of the work published by our group in the field of AS research can be found in the Publications tab and many more Projects are still ongoing.

How can you help?

To identify more genes associated with AS, and determine how they may cause disease, we’re looking for assistance!  We recruit both patients with AS as well as healthy controls (i.e people without any form of inflammatory arthritis) for our studies.  Participation involves a one-off blood or saliva sample for the extraction of DNA and RNA, and the completion of a short questionnaire.  Sometimes we can organise this via the post or we may ask participants to come to the Princess Alexandra Hospital to give their sample.  If you are interested in helping or would like more information on this project, please contact Linda Bradbury (nurse practitioner) on +61 7 3443 7078.

Image:

Fusion of adjacent vertebrae in the spine of an individual with severe ankylosing spondylitis.

Image credit:

Case courtesy of A.Prof Frank Gaillard, https://radiopaedia.org from the case https://radiopaedia.org/cases/7163


Team

Publications

  • Cortes, A., Hadler, J., Pointon, J.P., Robinson, P.C., Karaderi, T., Leo, P., Cremin, K., Pryce, K., Harris, J., Lee, S., Joo, K.B., Shim, S.C., Weisman, M., Ward, M., Zhou, X., Garchon, H.J., Chiocchia, G., Nossent, J., Lie, B.A., Førre, O., Tuomilehto, J., Laiho, K., Jiang, L., Liu, Y., Wu, X., , Elewaut, D., Burgos-Vargas, R., Stebbings, S., Appleton, L., Farrah, C., Lau, J., , Haroon, N., Ferreira, M.A., Yang, J., Mulero, J., Fernandez-Sueiro, J.L., Gonzalez-Gay, M.A., Lopez-Larrea, C., Deloukas, P., Donnelly, P., Bowness, P., Gafney, K., Gaston, H., Gladman, D.D., Rahman, P., Maksymowych, W.P., Xu, H., Crusius, J.B.A., Van Der Horst-Bruinsma, I.E., Chou, C.T., Valle-Oñate, R., Romero-Sánchez, C., Hansen, I.M., Pimentel-Santos, F.M., Inman, R.D., Videm, V., Martin, J., Breban, M., Reveille, J.D., Evans, D.M., Kim, T.H., Wordsworth, B.P., & (2013) Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nature Genetics, 45(7), pp. 730-738.
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  • Cortes, Adrian, Pulit, Sara L., Leo, Paul J., Pointon, Jenny J., Robinson, Philip C., Weisman, Michael H., Ward, Michael, Gensler, Lianne S., Zhou, Xiaodong, Garchon, Henri-Jean, Chiocchia, Gilles, Nossent, Johannes, Lie, Benedicte A., Førre, Øystein, Tuomilehto, Jaakko, Laiho, Kari, , Elewaut, Dirk, Burgos-Vargas, Ruben, Stebbings, Simon, Appleton, Louise, Farrah, Claire, Lau, Jonathan, Haroon, Nigil, Mulero, Juan, Blanco, Francisco J., Gonzalez-Gay, Miguel A., Lopez-Larrea, C, Bowness, Paul, Gaffney, Karl, Gaston, Hill, Gladman, Dafna D., Rahman, Proton, Maksymowych, Walter P., Crusius, J. Bart A., van der Horst-Bruinsma, Irene E., Valle-Oñate, Raphael, Romero-Sánchez, Consuelo, Hansen, Inger Myrnes, Pimentel-Santos, Fernando M., Inman, Robert D., Martin, Javier, Breban, Maxime, Wordsworth, Bryan Paul, Reveille, John D., Evans, David M., de Bakker, Paul I.W., & (2015) Major histocompatibility complex associations of ankylosing spondylitis are complex and involve further epistasis with ERAP1. Nature Communications, 6, Article number-7146.
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  • , , & Wordsworth, B. Paul (2016) Genetics of ankylosing spondylitis - Insights into pathogenesis. Nature Reviews Rheumatology, 12(2), pp. 81-91.
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  • Robinson, Philip C., Leo, Paul J., Pointon, Jennifer J., , Cremin, Katie, , Stebbings, Simon, , , Evans, David M., Wordsworth, Paul B., & (2016) Exome-wide study of ankylosing spondylitis demonstrates additional shared genetic background with inflammatory bowel disease. Genomic Medicine, 1, Article number-16008.
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  • Ellinghaus, David, Jostins, Luke, Spain, Sarah L., Cortes, Adrian, Bethune, Jörn, Han, Buhm, Park, Yu Rang, Raychaudhuri, Soumya, Pouget, Jennie G., Hubenthal, Matthias, Folseraas, Trine, Wang, Yunpeng, Esko, Tonu, Metspalu, Andres, Westra, Harm-Jan, Franke, Lude, Pers, Tune H., Weersma, Rinse K., Collij, Valerie, D'Amato, Mauro, Halfvarson, Jonas, Jensen, Anders Boeck, Lieb, Wolfgang, Degenhardt, Franziska, Forstner, Andreas J., Hofmann, Andreas, Schreiber, Stephan, Mrowietz, Ulrich, Juran, Brian D., Lazaridis, Konstantinos N., Brunak, Søren, Dale, Anders M., Trembath, Richard C., Weidinger, Stephan, Weichenthal, Michael, Ellinghaus, Eva, Elder, James T., Barker, Jonathan N.W.N., Andreassen, Ole A., McGovern, Dermot P., Karlsen, Tom H., Barrett, Jeffrey C., Parkes, Miles, , & Franke, Andre (2016) Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nature Genetics, 48(5), pp. 510-518.
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  • , Haynes, K., , , , Thomas, G.P., , , & (2017) Epigenetic and gene expression analysis of ankylosing spondylitis-associated loci implicate immune cells and the gut in the disease pathogenesis. Genes and Immunity, 18, pp. 135-143.
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