# Evaluation of First-Degree Relatives after Sudden Unexplained Death

> **NIH NIH K23** · LURIE CHILDREN'S HOSPITAL OF CHICAGO · 2020 · $189,370

## Abstract

PROJECT SUMMARY / ABSTRACT
Sudden unexplained death (SUD) is a tragic event and genetic disorders of heart rhythm and function have been
demonstrated in approximately 30% of SUD cases. Any SUD event is a dramatic signal that first-degree relatives
require risk stratification. Evaluation of first-degree relatives of a SUD victim is limited by several important gaps in
knowledge. First, studies have not prospectively evaluated the rate of transmitted versus de novo mutations in
SUD cases when data from molecular autopsy are available. The implications of molecular autopsy for surviving
family members depends on the probability of transmitted pathogenic variants. Second, when molecular autopsy
is not performed, the value of genetic testing remains unknown for first-degree relatives. Better genetic risk
stratification in this population will improve family diagnosis rates and improve counseling. Finally, genetic risk
stratification of pathogenic and likely pathogenic variants in families with SUD depends on expanding the list of
genes that may harbor pathogenic variants.
The project has three specific aims: 1) Determine the frequency of transmitted versus de novo pathogenic and
likely pathogenic variants in SUD; 2) Establish the yield of whole genome evaluation in phenotype-positive relatives
of a SUD victim; and 3) Use whole genome sequencing (WGS) to identify novel candidate genes associated with
SUD. The proposed research is innovative because it uses a close partnership between a multi-state consortium
of medical examiner's offices and a nationally-recognized clinical and genetics center to produce a detailed
genotype and phenotype evaluation of both SUD victims and their first-degree relatives using WGS. The proposed
research is significant because the data generated from this project will improve the evaluation and management
of first-degree relatives of SUD victims. Phenotype-genotype correlations will improve counseling. Finally, targeting
treatment to those relatives at highest risk for events should decrease further sudden death in the population.
This project will advance the candidate's overall training goal, which is to become an independent patient-oriented
researcher, with expertise in the genetic diseases that impact SUD. This grant supplements the candidate's
background in clinical research and public health by providing an opportunity for focused training in genetics and
bioinformatics. Through coursework and practical training in WGS, the candidate will achieve relevant expertise
and create a genotype-phenotype database that can be expanded to test additional hypotheses. The candidate's
exceptionally strong mentoring team at Northwestern University and the robust resources for translational genetic
research dedicated to Dr. Webster's training create a tremendous opportunity for career development and will
contribute to the long-term goal of decreasing mortality in first-degree relatives after a sudden unexpected death
event.

## Key facts

- **NIH application ID:** 9955313
- **Project number:** 5K23HL130554-04
- **Recipient organization:** LURIE CHILDREN'S HOSPITAL OF CHICAGO
- **Principal Investigator:** Robert Gregory Webster
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $189,370
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9955313

## Citation

> US National Institutes of Health, RePORTER application 9955313, Evaluation of First-Degree Relatives after Sudden Unexplained Death (5K23HL130554-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9955313. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*