Genomic Variant Interactions With Other Variants Or The Environment (UM1 Clinical Trials Not Allowed)

The National Institutes of Health (NIH), through the National Human Genome Research Institute (NHGRI), has announced its intention to release a Notice of Funding Opportunity (NOFO) for a new research initiative titled “Genomic Variant Interactions With Other Variants Or The Environment (UM1 Clinical Trials Not Allowed).” This initiative will be issued under opportunity number FOR-HG-25-020 and is currently classified as a forecasted discretionary funding opportunity. The program anticipates using a cooperative agreement funding instrument (UM1 activity code), which typically entails significant NIH involvement in project performance. The purpose of this upcoming initiative is to encourage research that explores how genomic variants interact with each other or with environmental factors, and how these interactions can influence biological outcomes. This research seeks to identify whether such interactions produce non-additive effects that can act as significant modifiers of variant impact. Applicants will be expected to develop and implement a research framework that facilitates experimental testing of specific variant combinations to detect these interactions. By uncovering patterns or structures within these interaction landscapes, the program aims to enhance the prediction accuracy of impactful variant interactions, which could significantly improve genome-wide association studies (GWAS) and the calculation of polygenic scores. As part of the program's collaborative structure, selected applicants will become members of the IGVF (Impact of Genomic Variation on Function) Consortium. Participants must commit to collaborative work, including coordination of assays, variants, and cell types, and the joint development of shared analytic strategies. Furthermore, all resources produced under this initiative are expected to be made broadly accessible to the scientific community and other stakeholders. The anticipated funding level for this initiative is $10 million in total program funding, with approximately five awards expected to be issued. However, the exact award ceiling and floor are not yet specified. The opportunity does not require matching funds. Eligible applicant types span a wide range, including U.S. and non-U.S. institutions, public and private higher education institutions, state and local government entities, for-profit and nonprofit organizations, and various tribal and housing authorities. Specifically, foreign organizations and components of U.S. organizations, as defined in the NIH Grants Policy Statement, are eligible to apply, provided they meet the scientific and collaborative expectations of the program. According to the forecast, the estimated date for posting the NOFO is June 23, 2025, with applications due by August 22, 2025. Awards are projected to be made by May 25, 2026, which is also the expected project start date. The opportunity is not offered on a rolling basis but is anticipated to recur annually or periodically, based on the nature of NIH program cycles. Interested parties are encouraged to begin preparing by developing collaborative frameworks and research proposals aligned with the goals of the IGVF Consortium. Inquiries regarding this funding opportunity may be directed to Mike Pazin at the National Human Genome Research Institute, reachable by phone at 301-480-2629 or via email at michael.pazin@nih.gov.

Applicants are encouraged to begin developing meaningful collaborations and project plans in anticipation of the formal NOFO.