Sequenziamento e studi di associazione su tutto il genoma per svelare i geni di suscettibilità al diabete di tipo 1.

During my third doctoral year, I worked in the Genome-Wide Association (GWA) and sequencing study of type 1 diabetes (T1D), directed by Prof. Francesco Cucca. The project aims to find type 1 diabetes risk loci using a large collection of Sardinian patients and controls. T1D is a multifactorial autoimmune disease, common in Sardinia, so the population is an appropriate cohort for the study. The GWA study design was a scan of 1,377 patients and 1,917 healthy unrelated controls genotyped with the Affymetrix 6.0 chip that contains over 900K single nucleotide polymorphisms (SNPs) across the genome. These data are then imputed with whole genome sequencing data from reference panels: our 508 sequenced Sardinian individuals, or 280 Europeans (of the 1000 genomes project), respectively. This let us test more than 13 million variants per person. Our analysis confirmed (P=1x10-5) several known associations outside the HLA region (PTPN22,CTLA4,IL2RAandINSgene). Imputation quality improved with the Sardinian reference panel. For instance, the INS gene association p-value increased from 7.3*10-8(1000 Genomes) to 5.5*10-13(Sardinian), suggesting that DNA sequencing data from a specific population improves accuracy of imputation in that population. To increase the chance to find new T1D susceptibility loci, we are expanding the dataset (to > 2,000 cases) and sequencing 1,200 Sardinian individuals for the reference panel.