Core Projects of FunGen-AD

De Jager, Philip L. (contact); St. George-Hyslop, Peter
Columbia University Health Sciences
Alzheimer variants: Propagation of shared functional changes across cellular networks
Montine, Thomas J. (contact); Kundaje, Anshul; Montgomery, Stephen Blair
Stanford University
Multi-omic functional assessment of novel AD variants using high-throughput and single-cell technologies
Shulman, Joshua M. (contact); Bellen, Hugo J.; Botas, Juan; Milosavljevic, Aleksandar
Baylor College of Medicine
Functional Genomic Dissection of Alzheimer’s Disease in Humans and Drosophila Models
Temple, Sally (contact); Harari, Oscar; Kampmann, Martin; Karch, Celeste Marie; Pumiglia, Kevin M.; Zuloaga, Kristen Leanne
Regenerative Research Foundation
Investigating the Functional Impact of AD Risk Genes on Neuro-Vascular Interactions
Vance, Jeffery Marvin (contact); Dykxhoorn, Derek Michael; Young, Juan Isaac; Griswold, Anthony
University of Miami School of Medicine
Functional genomic studies in diverse populations to characterize risk loci for Alzheimer Disease
Zhang, Xiaoling (contact); Wolozin, Benjamin L.
Boston University
Circular RNAs and their interactions with RNA-binding proteins to modulate AD-related neuropathology
Goate, Alison
Icahn School of Medicine at Mount Sinai
Genomic Approach to Identification of Microglial Networks Involved in AD Risk 
Mayeux, Richard P. (Contact); Miller, Gary W.; Vardarajan, Badri 
Columbia University
Epidemiological Integration of Genetic Variants and Metabolomics Profiles in Washington Heights Columbia Aging Project
Mayeux, Richard P. (Contact), Miller, Gary W.; Tosto, Giuseppe; Vardarajan, Badri N
Columbia University
Genetic Epidemiology and Multi-Omics Analyses in Familial and Sporadic Alzheimer’s Disease among Secular Caribbean Hispanics and Religious Order
Cruchaga, Carlos (Contact); Piccio, Laura
Washington University
Genetic Modifiers of Cerebrospinal Fluid TREM2 in Alzheimer’s Disease
Harari, Oscar
Washington University
Vance, Jeffery
University of Miami
Identifying Protective Variants in Local Ancestry of African Americans for ApoE4


The xQTL project

The xQTL project is a collaborative effort across the FunGen-AD, the AMP-AD, the NIH 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, CSF, and plasma. The multi-omic 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 the AD and the general scientific community.

Drs. Philip De Jager and Carlos Cruchaga are the leads for this project.

Collaboration with other consortia

The FunGen-AD investigators closely work with the ADSP geneticists, the ADSP ML/AI consortium, and the National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS) through working groups to coordinate efforts and create resources to support the mission of the ADSP. In addition, the FunGen-AD consortium engage and collaborate with the Accelerating Medicines Partnership® Alzheimer’s Disease (AMP® AD) and the NIH Center for Alzheimer’s and Related Dementias (CARD) through complementary approaches to accelerate translational research for AD/ADRD.

Working Groups

Functional Genomics Working Group

The Functional Genomics Working 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 Working Groups to ensure timely information exchange and identify opportunities for collaboration.

xQTL Working Group

The xQTL Working Group is a group of investigators that carry 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.

Data Standardization Working Group

The Data Standardization Working Group is a group of investigators that develop 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 definitions.
  • Define SOP for receiving data, quality check and maintenance.