Validating a combined geo-epidemiological approach to sampling for a geo-chemical disease (360G-Wellcome-091956_Z_10_A)

Podoconiosis (endemic, non-filarial elephantiasis) is a common but under-researched condition found predominantly in tropical Africa. A strong research program has been developed over six years through collaboration between academics from Addis Ababa University and Brighton & Sussex Medical School, and a podoconiosis Patient Association in southern Ethiopia. Through the research described below, we intend to expand the program to include geological and mineralogical research into the environmental trigger to complement further genetic studies. We plan first to use stored blood samples from patients and controls in southern Ethiopia to confirm the association between Class II HLA genes and susceptibility to podoconiosis. In parallel with this, we will collect salivary DNA samples from400 cases and 400 controls in a recently described endemic site in North West Cameroon. We will genotype the top 80 single nucleotide polymorphisms (SNPs) identified by our earlier GWAS and perform HLA fine mapping on all samples, and do HLA typing and sequencing in a subset. Finally, in an eight-site comparative study in four regions of Ethiopia, clinical, epidemiological, geological and topographical informationwill be gathered and linked using GIS methods, and soil and water samples taken for mineralogical and chemical analysis.