GENETICS OF SLE · Genetics of Systemic lupus erythematosus in northern and southern European populations

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease mediated by autoantibodies, which recognize nuclear and tissue specific antigens.The aetiology of this disease is incompletely determined. However, the risk to SLE has a significant genetic component, a conclusion supported by successful genome wide association studies (GWAS) in SLE published since 2008 - all were conducted in US-based cohorts. The variability within the“top hits” generated by each GWAS indicates the lack of power of these studies. In order to confidently define the full genetic architecture of SLE a significantly larger study will be required. My host laboratory is leading the effort in a well-powered GWA experiment in 5,500 SLE cases, collected from Northern and Southern Europe. First, high density SNP genotyping will be performed using Illumina Omni-Quad chip. I will participate in the ensuing genetic associations analyses on the data generated. Thereafter, I will make a meta-analysis of these GWAS data with the published GWAS in SLE in northern European populations and then to compare these data with the data of the southern European GWAS. We will seek replication for novel associations in additional samples available through the SLEGEN consortium. Finally I will select one novel locus in which to conduct functional studies that will help to clarify the role of the locus in SLE ethiopathogenesis.