Federal Grant Award Summary

Brigham & Women's Hospital Inc. received a $1,789,824 Project Grant from the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837), awarded July 15, 2026, with completion targeted for June 30, 2028. The project delivers an integrative computational-experimental research platform to advance cardiovascular disease (CVD) risk assessment by characterizing rare coding variants that influence lipid metabolism. The awardee will employ high-throughput functional screening using base and prime editing technologies to assess variants across 823 genes known to impact lipid phenotypes, systematically evaluating previously uncharacterized variants of uncertain significance in clinically relevant genes including LDLR, APOB, and PCSK9.

The project integrates functional screening data with large-scale population cohort information from the UK Biobank and All of Us Research Program to establish direct relationships between in vitro functional outcomes and real-world clinical phenotypes. This deliverable addresses a critical knowledge gap in CVD research by moving beyond genome-wide association study (GWAS) findings—which have identified over 400 lipid-associated loci—to identify specific causal genes and variants responsible for cholesterol regulation. The resulting insights are intended to enable development of individualized CVD risk assessments and support targeted clinical intervention strategies, ultimately improving the precision of cardiovascular risk prediction and treatment selection.