# Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants

> **NIH NIH U01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $1,237,762

## Abstract

Project Summary/Abstract
 There is growing societal and scientific interest in using genomic sequencing (GS) as screening to identify
genetic predispositions for disease early in life to prevent or mitigate future illness. There is, however,
skepticism about the clinical utility of GS in infants and concerns that it could lead to psychosocial harm,
unjustified health expenditures, and unnecessary healthcare utilization, with associated iatrogenic morbidity.
 Over the past five years, within the NIH-funded NSIGHT Consortium, our team launched the “BabySeq
Project,” the first randomized controlled trial (RCT) of GS in newborns. We implemented a clinical workflow for
whole exome sequencing, created criteria for returnable gene/variant selection and interpretation, curated a list
of 1,514 disease-associated genes with favorable validity, age of onset and penetrance; and designed novel
reporting formats. We enrolled and randomized 325 families to a family history (FH) arm or a FH+GS arm,
completed sequencing in the FH+GS arm, disclosed results to families and placed reports in the infants’
medical record. Our results were striking. Medically, we identified and disclosed unanticipated monogenic
disease risks in 11% of infants randomized to GS, and through follow-up testing revealed previously
undiscovered signs of underlying disease and unexplored family history in over half of these. We found no
increased distress or disruption to the parent-child relationship in response to receiving GS results and no
significant increases in downstream healthcare costs. Healthcare providers (HCPs) were able to constructively
manage the information reported. The BabySeq Project created a template for studying the psychological
impact, medical utility, and cost effectiveness of GS in healthy newborns.
 However, our BabySeq population was not diverse and thus our findings not generalizable. In order to
disseminate this technology equitably, it will be crucial to understand its impact on ethnically and racially
diverse populations. The goal of this study is to build on what we learned in BabySeq to study GS as screening
in a population of underserved, primarily African American and Hispanic, infants. We will return pathogenic GS
and copy number variation results and study the impact on families and HCPs, as well as the medical and
economic impact. Through this research we will develop, implement, and evaluate a sustainable approach to
GS as screening that leverages underserved community engagement to minimize distrust and maximize
benefit. This novel study provides a unique opportunity to determine medical, behavioral and economic
outcomes in an under-represented population of infants at three diverse CTSA sites, modeling the vision of GS
as a part of healthcare implemented early in childhood. This project is significant because it proposes to
generate much-needed evidence of the value of GS infants, innovative in its design as the first RCT to explore
the impact of WGS...

## Key facts

- **NIH application ID:** 10865032
- **Project number:** 5U01TR003201-04
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Robert C. Green
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,237,762
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10865032

## Citation

> US National Institutes of Health, RePORTER application 10865032, Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants (5U01TR003201-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10865032. Licensed CC0.

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