Core FunGen-AD Projects

Alzheimer Variants: Propagation of Shared Functional Changes Across Cellular Networks
De Jager, Philip L. (contact); St. George-Hyslop, Peter Henry
Columbia University Health Sciences
Project Period: July 15, 2021–June 30, 2026
Functional Genomic Studies in Diverse Populations to Characterize Risk Loci for Alzheimer Disease
Vance, Jeffery Marvin (contact); Dykxhoorn, Derek Michael; Young, Juan Isaac; Griswold, Anthony
University of Miami School of Medicine
Project Period: July 15, 2021 – June 30, 2026
Multi-Omic Functional Assessment of Novel AD Variants Using High-Throughput and Single-Cell Technologies
Montine, Thomas J. (contact); Kundaje, Anshul; Montgomery, Stephen Blair
Stanford University
Project Period: July 1, 2021 – June 30, 2026
Functional Genomic Dissection of Alzheimer’s Disease in Humans and Drosophila Models
Shulman, Joshua M. (contact); Bellen, Hugo J.; Botas, Juan; Milosavljevic, Aleksandar
Baylor College of Medicine
Project Period: July 1, 2021 – June 30, 2026
Investigating the Functional Impact of AD Risk Genes on Neuro-Vascular Interactions
Temple, Sally (contact); Harari, Oscar; Kampmann, Martin; Karch, Celeste Marie; Pumiglia, Kevin M.; Zuloaga, Kristen Leanne
Regenerative Research Foundation
Project Period: July 1, 2021 – June 30, 2026
Circular RNAs and Their Interactions with RNA-Binding Proteins to Modulate AD-Related Neuropathology
Zhang, Xiaoling (contact); Wolozin, Benjamin L.
Boston University
Project Period: July 1, 2021 – June 30, 2026
Genetic Epidemiology and Multi-Omics Analyses in Familial and Sporadic Alzheimer’s Disease among Secular Caribbean Hispanics and Religious Order
Mayeux, Richard P. (contact), Miller, Gary W.; Tosto, Giuseppe; Vardarajan, Badri
Columbia University
Project Period: June 1, 2020 – March 31, 2025
Epidemiological Integration of Genetic Variants and Metabolomics Profiles in Washington Heights Columbia Aging Project
Mayeux, Richard P. (contact); Miller, Gary W.; Vardarajan, Badri
Columbia University
Project Period: September 30, 2020 – August 31, 2024
Identifying Protective Genetic Variants for APOE4
Vance, Jeffery
University of Miami
Project Period: July 1, 2018 – March 31, 2023
Genetic Modifiers of Cerebrospinal Fluid TREM2 in Alzheimer’s Disease
Cruchaga, Carlos (contact); Piccio, Laura
Washington University
Project Period: July 15, 2018 – March 31, 2023
Genomic Approach to Identification of Microglial Networks Involved in Alzheimer Disease Risk
Goate, Alison
Icahn School of Medicine at Mount Sinai
Project Period: August 1, 2018 – July 31, 2023
Mendelian Randomization for Unbias Biomarker Discovery for AD and Other Complex Traits
Harari, Oscar
Washington University
Project Period: September 15, 2018 – May 31, 2023


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.

Work Groups

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.