U01HG011697

Polygenic Risk Score Diversity Consortium Coordinating Center - Project Summary

Polygenic risk scores (PRS) developed from analysis of large-scale genomic data in epidemiological studies hold promise as a precision medicine tool that will help identify individuals at higher disease risk. However, a critical challenge now facing PRS research and clinical translation is that most PRS have been developed using data from predominantly European-descent individuals, resulting in poorer predictive performance in non-European populations and reflecting the lack of diversity in genomic and biomedical research more broadly.

NHGRI is establishing a new Polygenic Risk Score Diversity Consortium to address this challenge by (1) leveraging existing diverse cohorts to improve PRS prediction across diverse, non-European populations and for a range of conditions and (2) optimizing the integration of large-scale genomic and phenotype datasets in support of collaborative analysis, reporting, and creation of methods and resources for the broader scientific community.

As the Coordinating Center, we will support the Consortium's goals by achieving four main aims:

1. Leading harmonization of genotype and phenotype data across Consortium study sites and affiliate members, including variant and sample level quality control, genotype imputation, and use of standard phenotype ontologies.

2. Organizing cross-consortium analysis and collaborative methods development, featuring standardized evaluation of PRS methods to identify consensus approaches, development of a local-ancestry informed PRS method, and integration of ethical, legal, and social implications (ELSI) considerations into analytic best practices.

3. Facilitating data sharing within and beyond the Consortium through community resources and repositories such as the NHGRI Genomic Data Science Analysis, Visualization, and Informatics Lab-Space (ANVIL), NCBI Database of Genotypes and Phenotypes (dbGaP), and the Polygenic Score Catalog.

4. Coordinating program logistics and outreach including through a Consortium website, in-person meetings, mentorship and training, and regular engagement with precision medicine partner programs.

We propose innovative approaches to achieve these four main aims, including leveraging emerging cloud-based platforms for harmonization, analysis, and sharing of large-scale genomic data; investigating scalable data science approaches to phenotype harmonization; leading a consortium-wide "bake-off" to establish consensus approaches to PRS generation and evaluation; and incorporating ELSI considerations into analytic best practices.

Furthermore, our application rests on 13 successful years of experience and expertise serving as coordinating centers for five large-scale genetic and biomedical projects. Through scientific and administrative leadership of this Consortium, we will help realize the public health benefit of developing PRS that predict and help prevent or mitigate a range of diseases in genetically diverse populations.

University Of Washington

NHGRI SUPPORTS THE DEVELOPMENT OF RESOURCES AND TECHNOLOGIES THAT WILL ACCELERATE GENOME RESEARCH AND ITS APPLICATION TO HUMAN HEALTH AND GENOMIC MEDICINE. A CRITICAL PART OF THE NHGRI MISSION CONTINUES TO BE THE STUDY OF THE ETHICAL, LEGAL AND SOCIAL IMPLICATIONS (ELSI) OF GENOME RESEARCH. NHGRI ALSO SUPPORTS THE TRAINING AND CAREER DEVELOPMENT OF INVESTIGATORS AND THE DISSEMINATION OF GENOME INFORMATION TO THE PUBLIC AND TO HEALTH PROFESSIONALS. THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM IS USED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM IS USED TO FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.172 - Human Genome Research

National Human Genome Research Institute (NHGRI) [HHS - NIH]

Seattle, Washington 981951016 United States

Single Zip Code

Polygenic Risk Score (PRS) Methods and Analysis for Populations of Diverse Ancestry Coordinating Center (U01 Clinical Trial Not Allowed) (RFA-HG-20-002)

Amendment Since initial award the total obligations have increased 254% from $2,332,345 to $8,262,832.