Kennedy Trust for Rheumatology Research Career Development Fellow
My research to date has largely focused on identifying genetic associations with diagnosis or disease presentation in inflammatory bowel disease (IBD), and developing statistical techniques to understand the function of genetic risk variants. As a field, statistical genetics has been very successful at finding risk variants for a host of complex diseases of the immune system. These risk variants tend to be shared across multiple immune diseases, and many of them are in genes involved in relevant immune pathways or expressed in relevant immune cells (such as monocytes and CD4 T-cells for IBD variants). However, we have had significantly less success in identifying the impact of genetic risk pathways on the function of the human immune system, and cross-disease analysis implies that these risk variants fall into a dizzying diversity of immune pathways. To translate disease genetics into real diagnostic, prognostic or treatment solutions we need to understand these pathways from genetic variation through healthy immune variation to disease risk. It is only through close collaborations between statistical geneticists, immunologists and molecular biologists that we will start to untangle these pathways.
My plan of research at the Kennedy Institute has three interrelated strands. The first is the analysis of large-scale human medical cohort data using statistical and computational techniques that are specifically designed to identify multi-gene signatures of shared underlying immune variation that drive a variety of different health outcomes. The second is to collaborate with other researchers to generate and analyse human immune variation data (including host immune function and exposure to both commensal and pathogenic organisms) in order to tie genetic risk of disease to variation in specific measurable immune phenotypes. The final strand is to collaborate with immunologists, cell biologists and clinical researchers to develop new ways of measuring the function of the human immune system in order to profile the specific pathways that confer genetic risk of chronic disease.
Genetic Complexity of Crohn's Disease in 2 Large Ashkenazi Jewish Families.
Levine AP. et al, (2016), Gastroenterology
Trinculo: Bayesian and frequentist multinomial logistic regression for genome-wide association studies of multi-category phenotypes.
Jostins L. and McVean G., (2016), Bioinformatics, 32, 1898 - 1900
Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.
Ellinghaus D. et al, (2016), Nat Genet, 48, 510 - 518
Inherited determinants of Crohn's disease and ulcerative colitis phenotypes: a genetic association study.
Cleynen I. et al, (2016), Lancet, 387, 156 - 167
Class II HLA interactions modulate genetic risk for multiple sclerosis.
Moutsianas L. et al, (2015), Nat Genet, 47, 1107 - 1113