The goals of the ADSP are to identify new genomic variants contributing to increased risk of developing late-onset Alzheimer’s disease (LOAD) and protection against developing AD; to better understand why individuals with known risk factor variants do not develop AD; and to examine these factors in multi-ethnic populations in order to identify new pathways for disease prevention. The ADSP is currently sequencing over 60,000 individuals from diverse ancestries as part of the ADSP-Follow-Up Study (ADSP-FUS), an initiative led by Dr. Margaret Pericak-Vance. Additional principal investigators for the project at the University of Miami Miller School of Medicine include Drs. Jeffery Vance, Michael Cuccaro and Brian Kunkle, supported by Drs. Eden Martin, Anthony Griswold and Gary Beecham. Principal investigators for the ADSP-FUS also include Drs. Badri Vardarajan and Richard Mayeux at Columbia University.
Since 2010, Dr. Pericak-Vance has also co-led efforts for the Alzheimer’s Disease Genetics Consortium (ADGC), which contributes data to the ADSP. In addition, Drs. Pericak-Vance and Eden Martin are principal investigators of the Collaborative for Alzheimer’s Disease Research (CADRE) which focuses on the analysis of ADSP data. Both ADGC and CADRE are funded by the NIA. The HIHG is also involved in multiple projects focusing on diverse populations, with the goal of addressing health disparities in genomic medical research.
Milestones
2020: The initial analysis of the ADSP whole-exome sequencing (WES) dataset in ~11,000 individuals with European and Caribbean Hispanic ancestry identified significant associations with functional rare variants in novel genes that provide further support for the roles of neuroinflammation (IGHG3) and transcriptional regulation (AC099552.4 and ZNF655) in AD. In addition, we identified novel associations with rare functional variants in previously established AD genes. These findings provide insight into disease mechanisms and targets for biological experiments to gain further understanding about the role of these genes in AD pathogenesis. (Bis et al. 2020)
2018: An analysis of whole genome sequencing (WGS) data was completed in 197 participants with European ancestry from 42 families. We identified multiple genes with functional rare variants that segregate with disease in multiplex AD families and showed that rare variation may influence AD risk at AD candidate genes. These results identify novel AD candidate genes and show a role for rare variation in LOAD etiology, even at genes previously identified by common variation. (Beecham et al. 2018)
2018: Analysis of WGS from 67 Caribbean Hispanic families in the discovery phase of the ADSP found a variant (p.R434W) in the previously identified AD candidate gene AKAP9 segregating with AD in two large families. Rare variants in a number of genes associated with LOAD in prior genome wide association studies were also identified, including CR1, BIN1 and SLC24A4. These results suggest that rare variants may underlie associations at some loci identified in genome wide association studies. (Vardarajan et al. 2018).
For a full list of ASDP publications and additional information please visit: https://www.niagads.org/adsp/adsp-publications