The decreasing cost and increasing robustness of genomic sequencing technologies offer an exceptional opportunity to advance the future of newborn screening (NBS) and increase the number of babies who have access to lifesaving interventions. Genomic newborn screening (gNBS), however, comes with many ethical, legal, and social implications (ELSI). A key determinant of benefits and risks of public health gNBS, at both individual and societal levels, is which genes are screened. The proposed study addresses this fundamental question: how should public health NBS programs decide which genes to screen? Existing gNBS studies provide a time-sensitive opportunity to obtain critical input from experts, yet it is also vital to consider viewpoints of other professional and community partners with a stake in gNBS. Understanding community preferences helps protect against missteps in the implementation of gNBS that could lead to mistrust and decreased uptake of NBS, which is the most universal and successful public health initiative in the United States. The first aim of this project is to appraise and contrast approaches and criteria used by experts conducting gNBS studies to determine which genes to screen. This aim will synthesize decision frameworks, key criteria (e.g., actionability, age of onset, penetrance), values (e.g., fairness, access), and lessons learned by gNBS researchers in their experience building gene panels. The second aim is to determine preferences and values of professional and community partners about decision-making for genes to include in gNBS. Informed by a deliberative public health approach, we will conduct engagement with 10 panels of engagement partners that include professionals, parents, and individuals living with genetic disorders to explore preferences and values about gene selection criteria and associated ELSI. The project outcome is guidance that is informed by a view of common interest on how to select genes to include in public health gNBS. We will leverage expert investigator experience at a time of high research concentration, while also closing a critical gap in ensuring integration of public, parent, patient, and professional preferences. Rather than developing a consensus gene list (which would require constant updating), the guidance will provide collectively defined decision-making values, gene selection criteria, and critical ELSI while characterizing areas without broad agreement for future study. The output of this study will guide ethical and appropriate decision-making as we prepare for future implementation of sequencing in public health NBS.