ADAPTT

Objectives: The overall goal of the planned analyses for ADAPTT is to better characterize the known genetic loci that are associated with AD/ADRD to identify the most probable functional elements responsible for the association. Most of these known associations have not been assigned to specific genes or functional variants.
We plan to analyze DNA variation from SNP array, whole exome and whole genome sequence data generated from participants that span the spectrum of dementia (with a focus on Alzheimer disease (AD) but also including MCI and related dementias [ADRD]) and participants without dementia (typically considered “controls”).

Study Design: We will evaluate these known loci, including the many genes underlying these associations, by integrating available genetic data, genomic data, in silico annotations, and multi-omic data using multiple different computational approaches. Our approaches will be sensitive to the different study designs of the contributing datasets (e.g. cohort studies, case-control studies, family-based studies). We will also examine a small number of these loci, prioritized by our analyses, using molecular genomic methods to better characterize the molecular mechanisms underlying the associations.

Collaboration: This is a collaboration with Drs. Martin, Pericak-Vance, and Vance at the University of Miami.

We are attempting to identify the inherited elements that contribute to Alzheimer disease risk. To do this we will analyze DNA sequence data from participants with Alzheimer disease and related dementias along with subjects who are cognitively normal. There are many known regions of the human genome that are associated with AD/ADRD risk, but the actual DNA sequence variations that are responsible for those associations remain unknown. Our goal is to use statistical and computer methods to identify the underlying responsible variations. For a small number of these, we will directly examine the biological mechanisms that help explain how those variations impact AD/ADRD.