Efficient IBD mapping for Alzheimer's Disease and related brain imaging phenotypes

Alzheimer’s Disease (AD) is a highly heritable complex human disease, but only a limited number of its genetic risk factors have been identified. In this project, we propose to leverage identical-by-descent (IBD) segments, which are expected to better tag haplotype effects and provide complementary genetic information to additively coded genotypes that are commonly used in genome-wide association studies, in the genetic association mapping for AD and related brain imaging endophenotypes. First, we will develop the statistical and computational framework for efficient genetic association mapping using IBD segments in large samples. We will then apply IBD mapping to identify novel genomic regions associated with AD and related brain imaging endophenotypes from the Alzheimer’s Disease Sequencing Project (ADSP), and combine association evidence from the UK Biobank and ADSP. We expect our novel tools and findings from this project to be made publicly available to facilitate novel discoveries that improve our understanding on the genetic architecture of AD and related brain imaging data.

Identical-by-descent segments inferred from genome-wide data provide information on population history and genetic relatedness that are not sufficiently used in current genetic association approaches. We propose to leverage identical-by-descent segments in the genetic association mapping for Alzheimer’s Disease and related brain imaging endophenotypes, develop efficient statistical methods and implement novel computational algorithms that can be applied to large samples. We expect our tools and findings to facilitate genetic research and provide novel insights into the genetic architecture of Alzheimer’s Disease.