Age-based genomic screening in newborns, infants, and children: a novel paradigm in public health genomics

Project Summary/Abstract
Genomic sequencing offers an unprecedented opportunity to identify clinically relevant genetic variants, yet
there are many challenges to overcome before this technology can be applied routinely in the healthy
population to identify individuals with actionable disorders in time to prevent or ameliorate symptoms. This
project explores an innovative age-based genomic screening (ABGS) paradigm that aims to provide targeted
and highly actionable genetic information to parents via their child’s routine wellness visits, thereby avoiding
some of the more difficult aspects of genome-scale sequencing while retaining most of the benefits. We will
utilize an established metric that evaluates parameters relevant to “clinical actionability” and defines the age of
onset and/or the age of intervention, to identify conditions that would be applicable for screening. In
collaboration with a diverse Expert Deliberative Group, we will define a consensus framework for carrying out
the ABGS program using targeted sequencing panels at specified time-points during infancy and childhood.
We will engage community stakeholders to raise awareness of the ABGS program and obtain critical feedback
to inform the development of accessible study materials. We will apply the Genetic Medicine Implementation
Research framework and utilize rigorous methods and measures to identify potential barriers and facilitators
and develop strategies to address them. Finally, we will conduct a pilot project in a small number of primary
care pediatrics clinics assessing preliminary outcomes, including perspectives of parents and providers, and
the feasibility, acceptability, and utility of ABGS. The expected result of this proposal is a validated,
stakeholder-informed, and practical ABGS program that includes hundreds of conditions that are actionable
throughout the lifespan, setting the stage for a future longitudinal study in a larger number of practices that can
assess clinical and health economic outcomes. Throughout this work, we will employ a community-based
participatory research approach to seek out perspectives from diverse stakeholders and emphasize the
importance of studying ABGS in a wide range of settings. The long-term goal of this research program is to
create a broadly applicable genomic screening program that extends well beyond newborn screening and can
be incorporated into routine well child care. We envision that this program will also prepare individuals to
eventually make informed decisions about the potential benefits and risks of screening for adult-onset
conditions during adulthood, thus creating a connection between genomic screening efforts in all age groups.

Grant Number: 5R01HG012271-04
NIH Institute/Center: NIH
Principal Investigator: JONATHAN BERG