New technologies for reliable and low-cost genome-wide genotyping and sequencing have led to many exciting genetic findings for human diseases in the past decade. In these studies, a critical element for success is that the sample size is large enough so that there is adequate power to detect genes with modest effect sizes at genome-wide significance. The Alzheimer’s Disease Genetics Consortium was formed in 2009 to collaboratively use the collective resources of AD research community to identify AD genes. The clinical, neuropathologic, molecular and statistical expertise exists within the AD research community. Also, much of the needed phenotype data and DNA samples also exist, gathered by the (now 32) NIA-designated AD research/core centers across the nation.
The goal of ADGC is to deconstruct the complete genetic architecture of Alzheimer’s disease (AD) and to determine how all inherited factors contribute to the AD phenotype. To this end, we will identify, annotate, replicate, and validate all DNA variants that increase risk or protect against AD, determine what genes are connected to these variants, and evaluate the contribution of each to total AD risk.
The Year 6-10 objectives include:
(1) expand AD genetics cohorts for non-Caucasian populations including African Americans, Latinos, and Asians;
(2) identify additional AD rare-variant genes using gene-based analyses; (3) perform whole exome sequencing and targeted sequencing on African American and Latino subjects to generalize findings made on Caucasians, to refine gene localization, to identify novel variants, and to identify novel genes found only in other ethnic groups; (4) assemble and harmonize phenotypes available in multiple cohorts to identify subtypes of AD and genes associated with variants associated with those subtypes.
Our lab is responsible for all IT and Data operations within ADGC, and sharing of published through collaboration between ADGC and NIAGADS. We also contribute to the analysis and interpretation of data.