Australian parental perceptions of genomic newborn screening for non-communicable diseases

Background: Newborn bloodspot screening (NBS) programs have improved neonatal healthcare since the 1960s. Genomic sequencing now offers potential to generate polygenic risk score (PRS) that could be incorporated into NBS programs, shifting the focus from treatment to prevention of future noncommunicable disease (NCD). However, Australian parents’ knowledge and attitudes regarding PRS for NBS is currently unknown.Methods: Parents with at least one Australian-born child under 18 years were invited via social media platforms to complete an online questionnaire aimed at examining parents’ knowledge of NCDs, PRS, and precision medicine, their opinions on receiving PRS for their child, and considerations of early-intervention strategies to prevent the onset of disease.Results: Of 126 participants, 90.5% had heard the term “non-communicable disease or chronic condition,” but only 31.8% and 34.4% were aware of the terms “polygenic risk score” and “precision medicine” respectively. A large proportion of participants said they would consider screening their newborn to receive a PRS for allergies (77.9%), asthma (81.0%), cancer (64.8%), cardiovascular disease (65.7%), mental illness (56.7%), obesity (49.5%), and type 2 diabetes (66.7%). Additionally, participants would primarily consider diet and exercise as interventions for specific NCDs.Discussion: The results from this study will inform future policy for genomic NBS, including expected rate of uptake and interventions that parents would consider employing to prevent the onset of disease

A multitiered analysis platform for genome sequencing: Design and initial findings of the Australian Genomics Cardiovascular Disorders Flagship

Purpose: The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD). Methods: Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS. The Flagship adopted a tiered approach to GS analysis. Tier 1 analysis assessed genes with established clinical validity for each cardiovascular condition. Tier 2 analysis assessed lesser-evidenced research-based genes. Tier 3 analysis assessed the functional impact of VUS that remained after tier 1 and tier 2 analysis. Results: Overall, a pathogenic or likely pathogenic variant was identified in 41% of participants with a cardiomyopathy, 40% with an arrhythmia syndrome, and 15% with a familial CHD/CHD+Extra Cardiac Anomalies. A VUS outcome ranged from 13% for arrhythmias to 34% for CHD/CHD+Extra Cardiac Anomalies participants. Tier 2 research analysis identified a likely pathogenic/pathogenic variant for a further 15 participants and a VUS for an additional 15 participants. Conclusion: The Flagship successfully facilitated a model of care that harnesses clinical GS and functional genomics for the resolution of VUS in the clinical setting. This valuable data set can be used to inform clinical practice and facilitate research into the future