Project ID CM-HD2023_30

ThemeCM-HD

Co Supervisor 1A School of MedicineWebsite

Co Supervisor 1B School of MedicineWebsite

Explaining the sexual dimorphism in Lupus through genetics

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects millions of people worldwide. Strikingly 9/10 SLE cases are women, yet little is understood as to why. Hormonal and environmental factors are believed to be partly responsible, and while there is strong evidence for a genetic basis for this dimorphism there is still a gulf in our understating. There are many avenues ripe for investigation and, with the advent of new technologies and a large amount of data available, a thorough study of the differences in genetics between the sexes is warranted. Current interests include the overlap between SLE associated genetic loci and genes showing sex differences in expression, genetic associations on the X chromosome and the cellular origins of effects.

This PhD will investigate all forms of genetic variation between the sexes that are informative of the sexual dimorphism of SLE, applying cutting edge statistical techniques on the richest data on SLE in the world. A background in statistics is not required but an interest in analyses is important. The student will learn the statistical language R and run modern genetic analyses software to a high standard making them very competitive in the current research environment. The study will use the largest collection of SLE genetic data in the world together with gene expression data from several sources including single cell data and very novel data on ChrX inactivation in SLE patients as part of the Open Targets project (https://www.opentargets.org/) in collaboration with the sanger institute.

Representative Publications

• Morris DL, Sheng Y, Zhang Y, Wang Y-F, Zhu Z, Tombleson P, Chen L, Graham D S-C, Bentham J, Chen R, Zuo X, Wang T, Wen L, Yang C, Liu L, Yang L, Li F, Huang Y, Yin X, Yang S, Rönnblom L, Fürnrohr BG, Voll RE, Schett G, Costedoat–Chalumeau N, Gaffney PM, Lau YL, Zhang X, Yang W, Cui Y, Vyse TJ. (2016). Genome-wide association meta-analysis in Chinese and European individuals identifies ten new loci associated with systemic lupus erythematosus. Nature Genetics. doi: 10.1038/ng.3603. Aug; 48(8): 940-946

• Bentham J, Morris DL, Graham DSC, Pinder CL, Tombleson P, Behrens TW, Martín J, Fairfax BP, Knight JC, Chen L, Replogle J, Syvänen A-C, Rönnblom L, Graham RR, Wither JE, Rioux JD, Alarcón-Riquelme ME & Vyse TJ. (2015). Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes genes in the pathogenesis of systemic lupus erythematosus Nature Genetics. doi:10.1038/ng.3434 Dec; 47(12) 1457-64