Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC)

The ADSP-PHC was established to harmonize the rich endophenotype data across cohort studies to enable modern genomic analyses of ADRD with the ultimate goal to generate harmonized data that will become a “legacy” dataset perpetually curated and shared NIAGADS. The ADSP-PHC will facilitate phenotypic data harmonization for ADSP participants with genetic and genomic data. This effort represents a multi-disciplinary approach leveraging interdisciplinary expertise in large-scale genetic and genomic studies, clinical neuroscience, neuroimaging, psychometrics, and bioinformatics. This study will utilize a team structure consisting of two coordinating centers to oversee activities of all harmonization teams and to oversee coordination with other ADSP workgroups and initiatives, a Storage and Informatics Core that will oversee the coordination between LONI and NIAGADS for all data storage, compliance, and dissemination, a CHARGE Coordination Core to oversee the alignment of data and protocols with CHARGE workgroups, an Integration & Analytics Core that will enable data integration across phenotypes to facilitate downstream machine learning applications, and eight Domain-Specific Harmonization Teams tasked with harmonization in their area of expertise. The endophenotypes that will be harmonized by this project include Cognition, Fluid Biomarkers, Amyloid PET, Structural MRI, White Matter Hyperintensities, White Matter Integrity, Vascular Risk Factors, and Neuropathology.

Site PIs on this project include: Jesse Mez (Boston University), Adam Brickman (Columbia University), Andy Saykin (Indiana University), Elizabeth Mormino (Stanford University), Pauline Maillard (UC Davis), Duygu Tosun-Turgut (UC San Francisco), Christos Davatzikos (University of Pennsylvania), Arthur Toga (USC); Mohamad Habes (University of Texas Health Science Center at San Antonio), Michael Cuccaro (University of Miami), Paul Crane (University of Washington), Bennett Landman (Vanderbilt University), Timothy Hohman (Vanderbilt University Medical Center), and Carlos Cruchaga (Washington University in St. Louis).

The growing availability of endophenotypic data in cohort studies of Alzheimer’s disease and related dementias (ADRD) provides an exciting opportunity to further characterize the genetic architecture of this devastating disease. However, there is a pressing need to develop and apply advanced harmonization approaches to align ADRD endophenotypes across cohorts. The goal of this coordinated national initiative – the AD Sequencing Project Phenotype Harmonization Consortium, or “ADSP-PHC” – is to provide a centralized database of robust endophenotypes for large-scale genomic analyses that will accelerate the identification of novel targets for therapeutic intervention in ADRD.