The Alzheimer’s Disease Sequencing Project (ADSP) Gene Verification Committee (GVC) systematically evaluates published human genetic evidence for genes and loci associated with Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD).
The GVC developed a structured framework for evaluating evidence across genetic study designs and uses expert review to distinguish well-supported genetic associations from findings that require additional evidence.
Explore the AD/ADRD Top Genes Repository
The AD/ADRD Top Genes Repository provides access to the GVC’s curated catalog of high-confidence genes and loci.
Researchers can use TopGenes to:
- Search and browse adjudicated genes and loci
- Explore the studies and genetic evidence supporting each finding
- Review GVC classifications and supporting information
- Download curated datasets for research use
Systematic Evaluation of AD/ADRD Genetic Evidence
The GVC developed and applied a systematic framework for evaluating the strength of genetic evidence for AD/ADRD loci and genes.
The framework was developed in two phases. In Phase 1, the GVC evaluated 23 nominated loci across multiple study designs to establish tiered criteria for assessing genetic evidence. In Phase 2, the framework was applied to 29 large-scale genome-wide studies published since 2015, resulting in the evaluation of 163 unique loci.
This systematic review identified 111 high-confidence loci/genes, supported by evidence including replicated associations across ancestries and convergent evidence from single-variant and variant-set analyses.
The resulting catalog highlights genetic evidence implicating biological processes including APP processing, microglial immunity, and lipid metabolism.
Publication
Comprehensive adjudication identifies 111 high-confidence loci for Alzheimer’s disease and related dementias
Leung YY, Marcora EM, Naj A, et al.
The manuscript describing the GVC framework and results is currently available as a medRxiv preprint and is undergoing peer review.
Read the preprintAbout the Gene Verification Committee
A large number of studies report genetic associations with AD and related dementias, but the strength of evidence supporting individual findings varies considerably. The GVC was established to systematically evaluate this evidence and identify genes and loci with strong genetic support.
This work provides a curated foundation for subsequent functional studies, biological interpretation, and therapeutic target discovery.
See GVC Committee on ADSeq.org