Dr Rebecca Sims
Powerful Study of Rare Variants in Alzheimer's disease
Alzheimer's disease & other dementias
Identifying and studying genes that contribute to Alzheimers disease (AD) development will help us to understand the causes of AD, providing the basis for developing new treatments. Common variation in nine novel genes are known to increase susceptibility to AD. However, these variants only account for roughly 32% of the genetic aetiology of the disease. Rare variation is thought to account for a proportion of the missing heritability. Next generation sequencing (NGS) allows the identification and analysis of rare variants (RV). However, NGS remains expensive and thus does not allow investigators to utilise suitably powered samples to comprehensively test RV across the genome for association with disease. This fellowship will investigate the role of RV in AD using a powerful case-control study. It will utilise a novel exome chip, designed using 12,000 exome sequences and the 1000 genomes project, to assay 300,000 genetic variants. It will develop new skill sets across genetics, bioinformatics and biostatistics to develop novel algorithms and programs to analyse RV. Thus, identifying novel loci that increase risk for AD which can be comprehensively investigated through cost effective, targeted sequencing and genotyping efforts, further elucidating the genetic architecture of AD.