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Pharmacogenetics and Inflammatory Diseases Research Group

Ankylosing spondylitis, gout, Crohn's disease, and ulcerative colitis are early onset, chronic inflammatory diseases which have no known cure. There has been a dramatic increase in these diseases within the last three decades and they are now a significant health issue for New Zealand.

Twin studies have demonstrated that these inflammatory diseases are multi-factorial conditions which have a strong genetic component. Moreover, the management of these diseases is complex and involves a plethora of drugs that require frequent adjustment and monitoring to minimise toxicity and non-response.

Poor control of these diseases is associated with excess morbidity, work absenteeism, and reduced employment opportunities.

Healthy colon, a colon of a person with Crohn's disease, and an X-ray of sacroiliitis
Left: Healthy colon. Middle: Colon of a person with Crohn's disease. Right: X-ray of sacroiliitis (inflammation of the sacroiliac joints).

Research focus

Examples of DNA sequence
Examples of DNA sequence.

The research focus of our research group is two-fold. We are interested in the identification and characterisation of genes that alter susceptibility to a range of chronic inflammatory diseases. Better understanding of these genes may help in both identifying environmental factors that trigger disease in genetically susceptible individuals, and in identifying novel drug targets that may assist in the development of new therapies.

Our research group is also interested in identifying genetic markers that can be used to predict response to current drug therapies used to manage these debilitating diseases.

No drug therapy is completely risk-free. Non-response and adverse drug reaction (ADR)-related costs often exceed the cost of the medications and can equate to 15–20% of a total hospital budget and up to 15% of hospital admissions. Identification of genetic variants that reliably associate with non-response or an ADR may enable the development of prospective genetic tests.

These tests have the potential to improve patients' quality of life whilst dramatically reducing healthcare costs.

Collaborations

We collaborate widely on a range of research projects that encompass pharmacogenetics and disease susceptibility genetics. Key collaborations include:

Application of genetics to the pathogenesis of common chronic conditions (HRC programme grant)

Principal investigators:  Associate Professor Greg Jones, Associate Professor Tony Merriman, Dr Rebecca Roberts

Objective: Study of genetic variability to advance the understanding of a range of common chronic conditions including abdominal aortic aneurysms, gout, rheumatoid arthritis, and IBD

Pharmacogenetics of thiopurine drugs in IBD

Principal investigator: Professor Murray Barclay (Department of Medicine, UOC), Australian and New Zealand IBD Consortium
Objective: Identification of robust genetic markers of non-response and/or ADRs for thiopurine drugs in Crohn’s disease and ulcerative colitis

Spondyloarthritis genetics and environment (SAGE) study

Principal investigator: Dr Simon Stebbings (Department of Medicine, DSM)
Objective: Investigation of the incidence, prevalence, clinical spectrum, socio-economic burden, and risk genes of Spondyloarthritis

Pharmacogenetics of allopurinol

Principal investigator: Professor Lisa Stamp (Department of Medicine, UOC)
Objective: Identification and characterisation of genetic variants that alter response to allopurinol in patients with gout

Oral Crohn's disease

Principal investigator: Professor Anita Nolan (Auckland University of Technology)
Objective: Identification of genotypes in patients with oral Crohn’s disease which predict development of subsequent intestinal disease

Funding

Our group is currently funded by the Health Research Council of New Zealand project grant which is part of a larger HCR programme grant exploring the application of genetics to the study of common chronic disease.

Contact us

For all enquiries, please contact Dr Rebecca Roberts:

Email rebecca.roberts@otago.ac.nz

Selected publications

Jostins, L., Ripke, S., Weersma, R. K., Duerr, R. H., McGovern, D. P. B., Hui, K. Y., … Gearry, R., … and also Barclay, M., Roberts, R. (2012). Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491(7422), 119-124. doi: 10.1038/nature11582

Roberts, R. L., & Barclay, M. L. (2012). Current relevance of pharmacogenetics in immunomodulation treatment for Crohn's disease. Journal of Gastroenterology & Hepatology, 27(10), 1546-1554. doi: 10.1111/j.1440-1746.2012.07220.x

Stamp, L. K., Hazlett, J., Roberts, R. L., Frampton, C., Highton, J., & Hessian, P. A. (2012). Adenosine receptor expression in rheumatoid synovium: A basis for methotrexate action. Arthritis Research & Therapy, 14, R138. doi: 10.1186/ar3871

Eglinton, T. W., Roberts, R., Pearson, J., Barclay, M., Merriman, T. R., Frizelle, F. A., & Gearry, R. B. (2012). Clinical and genetic risk factors for perianal Crohn's disease in a population-based cohort. American Journal of Gastroenterology, 107(4), 589-596.
doi:10.1038/ajg.2011.437

Stamp, L. K., & Roberts, R. L. (2011). Effect of genetic polymorphisms in the folate pathway on methotrexate therapy in rheumatic diseases. Pharmacogenomics, 12(10), 1449-1463. doi: 10.2217/pgs.11.86

Rivas, M. A., Beaudoin, M., Gardet, A., Stevens, C., Sharma, Y., Zhang, C. K., … and also Barclay, M., Roberts, R., Gearry, R. (2011). Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nature Genetics, 43(11), 1066-1073. doi: 10.1038/ng.952

Roberts, R. L., van Rij, A. M., Phillips, L. V., Young, S., McCormick, S. P. A., Merriman, T. R., & Jones, G. T. (2011). Interaction of the inflammasome genes CARD8 and NLRP3 in abdominal aortic aneurysms. Atherosclerosis, 218(1), 123-126. doi: 10.1016/j.atherosclerosis.2011.04.043

Roberts, R. L., Hollis-Moffatt, J. E., Gómez-García, M., Fransen, K., Ponsioen, C. Y., Crusius, B. A., … Merriman, T. R., Barclay, M. L., Gearry, R. B., Alizadeh, B. Z. (2011). Association of the protein-tyrosine phosphatase nonreceptor type substrate 1 (PTPNS1) gene with inflammatory bowel disease. Inflammatory Bowel Diseases, 17(2), E19-E21. doi: 10.1002/ibd.21470

Anderson, C. A., Boucher, G., Lees, C. W., Franke, A., D’Amato, M., Taylor, K. D., … Barclay, M., … Roberts, R., … Gearry, R., … Rioux, J. D. (2011). Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nature Genetics, 43(3), 246-254. doi: 10.1038/ng.764

Roberts, R. L., Gearry, R. B., & Barclay, M. L. (2010). Allopurinol-thiopurine combination therapy in inflammatory bowel disease: are there genetic clues to this puzzle? Pharmacogenomics, 11(11), 1505-1508. doi: 10.2217/pgs.10.143

Franke, A., McGovern, D. P. B., Barrett, J. C., Wang, K., Radford-Smith, G. L., Ahmad, T., … Roberts, R., … Barclay, M., … Gearry, R., … Parkes, M. (2010). Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nature Genetics, 42(12), 1118-1125. doi: 10.1038/ng.717

Simms, L. A., Doecke, J. D., Roberts, R. L., Fowler, E. V., Zhao, Z. Z., McGuckin, M. A., … McCallum, R., … Barclay, M. L., Gearry, R. B., Merriman, T. R., … Radford-Smith, G. L. (2010). KCNN4 gene variant is associated with ileal Crohn's disease in the Australian and New Zealand population. American Journal of Gastroenterology, 105(10), 2209-2217. doi: 10.1038/ajg.2010.161

Stamp, L. K., Chapman, P. T., O'Donnell, J. L., Zhang, M., James, J., Frampton, C., Barclay, M. L., Kennedy, M. A., Roberts, R. L. (2010). Polymorphisms within the folate pathway predict folate concentrations but are not associated with disease activity in rheumatoid arthritis patients on methotrexate. Pharmacogenetics & Genomics, 20(6), 367-376. doi: 10.1097/FPC.0b013e3283398a71

Bentley, R. W., Cleynen, I., Gearry, R. B., Barclay, M. L., Rutgeerts, P., Merriman, T. R., … Roberts, R. L., Vermeire, S. (2010). Evidence that glioma-associated oncogene homolog 1 is not a universal risk gene for inflammatory bowel disease in Caucasians. Genes & Immunity, 11(6), 509-514. doi: 10.1038/gene.2010.15

Bentley, R. W., Pearson, J., Gearry, R. B., Barclay, M. L., McKinney, C., Merriman, T. R., & Roberts, R. L. (2010). Association of higher DEFB4 genomic copy number with Crohn's disease. American Journal of Gastroenterology, 105(2), 354-359. doi: 10.1038/ajg.2009.582

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