Rare genetic variants in associated genes to Alzheimer´s disease in Spanish population

Rare genetic variants contribute to an undetermined fraction of Alzheimer’s disease (AD) heritability. They are mostly located in coding regions and therefore they typically have a much greater phenotypic impact than common variants; so its translational potential has been shown as high in AD. These variants are very specific to particular populations and their frequency differs significantly by geographic area. In our country no genomic studies have been performed to address this issue in Alzheimer’s disease. Our goal is to detect rare genetic variants associated with Alzheimer’s disease through two complementary methods: next generation sequencing and exome chip. To accomplish this goal we will use the large sample of our national consortium Dementia GEnetic Spanish Consortium (DEGESCO), which includes one of the largest collections of DNA from neurodegenerative disease in Europe. On the one hand we aim to describe the most prevalent rare variants in the Spanish population by resequencing of 29 loci associated with AD in a sample of patients with early onset AD. Complementarily we will use an exome chip specifically designed for capturing rare variants typical of our country that would allow us to detect new variants associated with the disease in our population.