Polygenic RIsk MEthods in Diverse populations (PRIMED) Consortium

Data Sharing
Co-chairs: Whitney Hornsby and Yuji Zhang

Scope: The Data Sharing WG will collaborate on developing policies and processes to share data within the PRIMED Consortium. The data to be shared include individual-level genotype and phenotype data (source and harmonized) and summary statistics from the studies and consortia proposed by the study sites for either PRS development or validation. An initial priority for this WG will be to understand the opportunities and constraints for intra-consortium sharing of the studies and consortia proposed by study sites, especially those governed by groups not affiliated with the PRIMED Consortium. The policies and processes developed by this WG will need to facilitate sharing within consortium workspaces on the AnVIL platform and anticipate subsequent data release to the scientific community, also on AnVIL. Initially, the WG scope will include both technical aspects of data sharing (e.g., the establishment of AnVIL workspaces) and policy aspects (e.g., data use limitations).

Methods
Co-chairs: Linda Kachuri, Bogdan Pasanuic, and Haoyu Zhang

Scope: The Methods Working Group is a forum where PRIMED investigators introduce, develop, and disseminate new PGS methodologies to address disparities. The WG prioritizes methods that leverage cross ancestry information to improve the transferability of PRS across diverse populations. A key focus is the collaborative development, application, and evaluation of PRS approaches in diverse populations, with special consideration for admixture. The WG will identify key methodological topics as they may arise (e.g., admixture-centric PRS; functionally-informed PRS, etc) and provide opportunity for cross-Consortium discussion and collaboration to address these topics. Measures of the success of the WG will be the development of new methods as well as Consortium generated documentation and recommendations on best practices for PRS use in diverse populations. Projects will be disseminated to PRIMED and the broader community through peer-reviewed publications where appropriate.

Data Analysis
Co-chairs: Alisa Manning, Ethan Lange, Megan Shuey, Jonathan Shortt, and Aniruddh Patel

Scope: The Data Analysis Working Group provides guidance, resources, and support to cross-Consortium and prioritized Consortium projects in PRIMED. This WG will create instructions and best-practices to guide projects in their use of AnVIL, maintain data harmonization procedures, and update data standards. With the goal of supporting cross-Consortium and prioritized Consortium projects, the WG focuses on helping analysts identify and use genotype and phenotype data, and assists with developing harmonization plans when needed. In collaboration with analysts, the WG will identify roadblocks to performing analysis, brainstorm potential solutions, and facilitate cross-WG collaboration when additional input is needed.

Population Descriptors, Social and Ethical Implications (POPSEI)
Co-chairs: Genevieve Wojcik, Braxton Mitchell, and Iain Konigsberg

Scope: The Population Descriptors, Social and Ethical Implications (POPSEI) Working Group will identify, investigate, and respond to ethical, social, and related considerations that may arise over the course of the PRIMED Consortium. The development and use of polygenic risk scores (PRS) constitutes an exciting new scientific area but is fraught with numerous challenges related to equity application across diverse ancestral groups and suitability for clinical use, among others. The WG will identify specific challenges and opportunities to address, provide structured discussions around each issue, and propose specific follow-up plans to include, as appropriate, follow-up discussion with other WGs, feedback to the Steering Committee, and outreach via publications and commentaries to the broad scientific community. The WG will additionally serve as a resource to PRIMED investigators, Study Sites, and WGs on social and ethical implications as well as population descriptor considerations in PRIMED projects and manuscripts. The WG will also provide guidance and support to PRIMED investigators, Study Sites, and Working Groups on the selection, use, and discussion of population descriptors in PRIMED projects and manuscripts. 

Social Determinants of Health (SDoH)
Co-chairs: Leslie Lange and David Conti

Scope: The Social Determinants of Health (SDoH) WG will be responsible for identifying and defining relevant SDoH and other environmental phenotypic measures to be considered for use in PRIMED. This will occur through literature review, input from internal and external investigators with relevant expertise, conducting needs assessment among PRIMED study sites, and reviewing data resources to ascertain availability of SDoH variables across the proposed PRIMED datasets. The WG will partner with external experts and other translationally focused consortia (e.g. eMERGE, ClinGen) to produce a set of recommendations on incorporation of SDoH variables in PRS methods development and thoughtful consideration of these measures in interpretation and clinical translation of PRSs. The SDoH WG will also work closely with the Methods Development WG in consideration of SDoH variables in PRS methods development and contextualizing PRS implementation, and with additional WGs (e.g. SEIPR and Population Descriptors) to ensure that social and ethical considerations from these WGs are incorporated into variable selection, use, and interpretation in PRIMED.

RFA-HG-20-001: Polygenic Risk Score (PRS) Methods and Analysis for Populations of Diverse Ancestry – Study Sites (U01 Clinical Trial Not Allowed)

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

Press Release: NIH awards $38 million to improve utility of polygenic risk scores in diverse populations
June 26, 2021