Core FunGen-AD Projects
The xQTL Project
Quantitative trait loci (QTL) are genetic regions that influence phenotypic variation of a molecular (transcriptomic, proteomic, lipidomic among others) trait. The xQTL project is a collaborative effort across the FunGen-AD, the Accelerating Medicines Partnership Alzheimer’s Disease (AMP AD), the NIH Center for Alzheimer’s and Related Dementias (CARD), and the ADSP.
The goal of the xQTL project is to generate a reference map of AD-related QTLs to determine the effect of genetic variation on molecular traits. This project builds on existing datasets from multiple omics layers, including bulk and single-cell transcriptomics, epigenomics, proteomics, lipidomics, and metabolomics and from multiple tissues including brain, cerebrospinal fluid (CSF), and plasma. The multi-omics approach will enable mapping the propagation of functional consequences of each variant, which will be instrumental to identifying the causal gene(s) in each locus as well as novel biomarkers and therapeutic targets for AD/ADRD. The xQTL reference map will be made available to both the AD and general scientific communities.
Collaboration with Other Consortia
The FunGen-AD investigators closely work with the ADSP geneticists, the ADSP AI/ML Consortium, and the National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS) through work groups to coordinate efforts and create resources to support the mission of the ADSP. In addition, the FunGen-AD consortium engages and collaborates with the AMP-AD and CARD through complementary approaches to accelerate translational research for AD/ADRD.
Functional Genomics All-Hands Work Group
The Functional Genomics Work Group consists of ADSP investigators who are conducting or interested in projects that study functional impacts of AD genes or variants.
The group was formed in summer of 2020. Current activities include the following:
- Serve as a venue to coordinate ongoing functional genomic efforts within the FunGen-AD and with other relevant consortia to facilitate synergy and collaboration.
- Develop a consensus list of loci with prioritized variants and genes based on human genetic data and existing evidence to support functional annotation.
- Identify current gaps in knowledge where additional resources may be most impactful.
- Disseminate prioritized target genes and variants to facilitate the work of other AD investigators and the broader research community pursuing functional studies.
- Communicate with other ADSP work groups to ensure timely information exchange and identify opportunities for collaboration.
xQTL Work Group
The xQTL Work Group carries out the activities defined in the xQTL Project. The group was formed in spring of 2021. Current activities include the following:
- Catalog and gather genetic, genomic, and multi-omic data that have been generated by its members and other relevant datasets that are publicly available.
- Process and harmonize these data for integration and analysis.
- Identify analytical methods for QTL mapping and integration across multi-omic data types.
- Conduct analyses.
- Develop manuscripts.
Data Standardization Work Group
The Data Standardization Work Group develops data standards to facilitate data collection, integration, and sharing with the AD and the broader research community. The group was formed in summer of 2021. Current activities include the following:
- Define data format and meta-data.
- Define standard operating procedures (SOPs) for receiving data, quality checks, and maintenance.