Integrating Genetics and Genomic Technology for Early Cardiac Risk Detection: Advances and Implications

According to new research from Northwestern Medicine, a composite genetic risk approach combining monogenic, polygenic, and noncoding regulatory signals may improve risk stratification for arrhythmia and sudden cardiac death in research cohorts.

Rather than relying solely on symptom-based detection, the proposed framework enables presymptomatic risk estimation through integrated genomic profiling.

The composite score was derived and internally validated using a curated cohort. It incorporated rare pathogenic and likely pathogenic variants, polygenic risk burden, and rare regulatory variants to better discriminate individuals at elevated risk. Compared with single-modality genetic approaches, this model improved net reclassification and odds of disease in the top decile of risk.

While still investigational, the approach suggests a roadmap for genomic risk deployment in clinical settings. Potential implementation could combine targeted gene panels or genome-wide sequencing with validated polygenic scoring, standardized variant interpretation, and protocolized reporting of actionable findings.