Comparing the genetic architecture of autoimmune diseases

Autoimmune diseases affect ~10% of the population worldwide and they have no cure. Currently available immunomodulatory drugs can help to alleviate symptoms, but have variable efficacy and can lead to severe side effects. Progress in identifying the genetic determinants of autoimmune and immune-mediated diseases is helping to improve our knowledge of the pathophysiological mechanisms that underlie these conditions. The key research interests of my group are to better understand the architecture of genetic predisposition across different autoimmune and immune-mediated diseases, and to explore the functional relevance and potential clinical utility of such cross-comparisons.   

Assessing patterns of genetic association between autoimmune diseases to date reveals heterogeneity, but also a few key variants that are emerging as immunopathological foci. We aim to investigate shared molecular circuits and cellular mechanisms across conditions for the purpose of identifying immunological ‘hubs’ that may be targeted therapeutically via drug repositioning approaches.

A further aim is to interrogate the relationship between genetic variation and the spatiotemporal dynamics of immune cell responsiveness, and how this may parallel the spectrum of immune-mediated diseases spanning malignancies, autoimmunity and infections. Elucidating these relationships can have implications for precision medicine in the context of patient stratification, prognostication, and optimal drug dosaging to balance efficacy and side effects.

The Dendrou group is supported by the Wellcome Trust and the Royal Society through a Sir Henry Dale Fellowship.

Potential project areas: Autoimmunity, genomics, immunology, single cells, gene regulation, precision medicine 

Selected publications

CORTES A*DENDROU CA*, MOTYER A, JOSTINS L, VUKCEVIC D, DILTHEY A, DONNELLY P, LESLIE S, FUGGER L, MCVEAN G. 2017. Bayesian analysis of genetic association across tree-structured routine healthcare data in the UK Biobank. Nat Genet49 (9), pp. 1311-1318.

DENDROU CA, MCVEAN G, FUGGER L. 2016. Neuroinflammation - using big data to inform clinical practice. Nat Rev Neurol12 (12), pp. 685-698.

DENDROU CA, CORTES A, SHIPMAN L, EVANS HG, ATTFIELD KE, JOSTINS L, BARBER T, KAUR G, KUTTIKKATTE SB, LEACH OA . 2016. Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity. Sci Transl Med8 (363), pp. 363ra149.

DENDROU CA, FUGGER L, FRIESE MA. 2015. Immunopathology of multiple sclerosis Nat Rev Immunol15 (9), pp. 545-558.

DENDROU CA, BELL JI, FUGGER L. 2013. Weighing in on autoimmune disease: Big data tip the scale. Nat Med19 (2), pp. 138-139.

GREGORY AP*DENDROU CA*, ATTFIELD KE, HAGHIKIA A, XIFARA DK, BUTTER F, POSCHMANN G, KAUR G, LAMBERT L, LEACH OA . 2012. TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis. Nature488 (7412), pp. 508-511.