Federal Grant Award Summary

The National Heart, Lung, and Blood Institute (NHLBI) awarded Indiana University a Project Grant of $516,592 (awarded July 1, 2026; completion April 30, 2030) under the Cardiovascular Diseases Research program (CFDA 93.837) to conduct integrative genomic analysis and develop high-dimensional risk prediction models for congenital heart defects (CHDs). The research leverages novel random field statistical methods to address the complex, interactive, and multi-omic etiology of CHDs by analyzing samples from three major federal biobanks: the National Birth Defects Prevention Studies (NBDPS), the Pediatric Cardiac Genomics Consortium (PCGC), and the Trans-Omics for Precision Medicine (TOPMed) CHD Biobank. The project's primary deliverables include identification and replication of genomic regions associated with CHD risk in the context of disease heterogeneity and genetic interactions, detection of methylation and expression quantitative trait loci, and discovery of biological pathways integrating multi-omic factors to advance understanding of CHD development mechanisms.

This research directly addresses a significant gap in the field: while genome-wide association studies and whole-genome sequencing have identified individual genetic variants associated with CHDs, the complex interactions during embryogenesis and rare genetic variants with heterogeneous effects have remained poorly understood, resulting in disease risk prediction models with limited clinical utility. By applying advanced computational methods to existing federal research resources, the project aims to substantially improve CHD risk stratification and provide evidence-based insights into disease etiology to inform clinical practice and prevention strategies.