Disease Mechanisms: Genetic data sharing (Milestone 2.G)
Achieved
Timeline Start - End
2018 - 2024Research Implementation Area
Research on Disease MechanismsMaximize the translational potential of genetics research by ensuring rapid and broad sharing of large-scale genetic/genomic data, similar to the open science, data sharing model of the AMP AD program and by supporting programs focused on:
- Understanding the mechanisms by which genetic variants (including ApoE) discovered through GWAS and sequencing studies influence AD risk
- Integrating genomic data with other multi-omics data from brain, peripheral tissues, and iPSC cellular models from well-phenotyped cohorts
- Establishing the gene-basis and directionality for genetic variant association so gene networks can be annotated with causality as tools for drug discovery.
Success Criteria
- Launch an open science research program focused on generating knowledge on the mechanisms by which genetic variants influence AD risk and the directionality for genetic variation association. Develop gene networks that are annotated with causality as open source analytical tools for drug discovery.
Summary of Key Accomplishments
NIA is advancing the achievement of this milestone is in two major ways: by investing in genetics research aimed at resolving the complex genetics of AD, and by launching targeted initiatives aimed at understanding the mechanisms by which genetic variants influence AD risk and resilience. These programs support cutting-edge molecular and cellular biology research, as well as artificial intelligence methods. The Alzheimer’s Disease Sequencing Project Functional Genomics Consortium supports a team-science strategy and applies genome-wide approaches to discover and characterize functional genomic and epigenomic elements and elucidate and validate their roles and the mechanisms of action underpinning Alzheimer’s disease and related dementias (AD/ADRD).
The key accomplishments summary is current as of July 2022.
Accomplishments/Implementation Activities
Funding Initiatives
- PAR-14-070: Limited Competition: Renewal of, and Revisions to, the Alzheimer's Disease Genetics Consortium (U01)
- PAR-18-889: Limited Competition: Renewal of, and Revisions to, the Alzheimer's Disease Genetics Consortium (U01)
- PAR-16-406: Limited Competition: Additional Sequencing for the Alzheimer's Disease Sequencing Project (U01)
- RFA-AG-16-001: NIA Coordinating Center for Genetics and Genomics of Alzheimer's Disease (U54)
- RFA-AG-16-002: Alzheimer's Disease Sequencing Project (ADSP) Replication Phase Analysis Studies (U01)
- PAR-17-214: Limited Competition: Analysis of Data from NIA's Alzheimer's Disease Sequencing Project Follow-Up Study (U01)
- RFA-AG-17-010: From Association to Function in the Alzheimer’s Disease Post-Genomics Era (R01)
- RFA-AG-18-026: From Association to Function in the Alzheimer’s Disease Post-Genomics Era (R01)
- RFA-AG-17-053: Human Cell Biology of Alzheimer's Disease Genetic Variants (R01)
- PAR-18-516: Human Cell Biology of Alzheimer's Disease Genetic Variants (R01)
- PAR-18-596: Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01)
- NOT-AG-18-001 (#4): Genetic Underpinnings of Endosomal Trafficking as a Pathological Hub in AD/ADRD
- RFA-AG-18-013: Continuation of the AMP AD Target Discovery and Preclinical Validation Consortium (U01)
- RFA-AG-18-014: Limited Competition: Data Coordinating Center for the Accelerating Medicines Partnership Target Discovery and Preclinical Validation Consortium AMP AD DCC (U24)
- PAR-18-889: Limited Competition: Renewal of, and Revisions to, the Alzheimer's Disease Genetics Consortium (U01 Clinical Trial Not Allowed) (Reissue of PAR-14-070)
- PAR-19-269: Cognitive Systems Analysis of Alzheimer's Disease Genetic and Phenotypic Data (U01 Clinical Trial Not Allowed)
- RFA-AG-21-006: Alzheimer’s Disease Sequencing Project Functional Genomics Consortium (U01 Clinical Trial Not Allowed)
Research Programs and Resources
- AMP AD Target Discovery and Preclinical Validation Project
- Agora: AMP AD’s Web-based Interactive Platform
- NIA Alzheimer's Disease Genetics Portfolio
- Alzheimer’s Disease Sequencing Project (ADSP)
- NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS)
- Functional genomic studies in diverse populations to characterize risk loci for Alzheimer Disease
- Investigating the Functional Impact of AD Risk Genes on Neuro-Vascular Interactions
- Identifying Protective Genetic Variants for APOE4
- Center for Alzheimer's and Related Dementias (CARD): iPSC Neurodegenerative Diseases Initiative
- Long-read DNA sequencing of Alzheimers Disease and Related Dementias cases
- Multi-omic functional assessment of novel AD variants using high-throughput and single-cell technologies
- Projects funded under RFA-AG-21-006