Mapping Health Futures: Genomic Screening and its Population Impact

At the PRECISE-IHCC Conference, jointly organised by Precision Health Research, Singapore (PRECISE) and the International Health Cohorts Consortium (IHCC), speakers discussed advancements and ethical considerations in genomic screening. Dr Chien Yin Hsiu, Director of Newborn Screening, National Taiwan University Hospital, and Professor Martin Delatycki, Co-Director of Bruce Lefroy Centre, Murdoch Children’s Research Institute, highlighted opportunities offered by newborn and reproductive carrier genomic screening. Meanwhile Professor Thong Meow Keong, Clinical Geneticist Consultant, Genetic Medicine Unit, University of Malaya Medical Centre addressed the ethical challenges involved in implementing these screenings.

Safeguarding Newborn Health through Genomic Screening

Dr Chien Yin Hsiu began with an overview of the current newborn screening landscape in Taiwan. She outlined the progress made since the programme’s introduction in 1984—both in the range of diseases screened and the number of newborns included. These developments have significantly reduced the lead time from testing to follow-up, diagnosis, and treatment.

Explaining the significance of this evolution, Dr Chien said, “Newborn screening is a vital public health tool for early detection and intervention of inherited genetic conditions. For instance, our study shows that the prognosis for patients with citrin deficiency improves significantly when identified early through newborn screening, rather than waiting for symptoms to appear in infants. And citrin deficiency is just one of over 50 conditions we screen for today. That is why we are strongly motivated to improve newborn screening continually.”

Notably, technology has played a critical role in early detection. Innovations such as next generation sequencing (NGS) provide more accurate and conclusive findings to facilitate timely intervention. By demonstrating how a single test is capable of screening for multiple diseases simultaneously, Dr Chien highlighted how these technologies not only simplify testing but also indirectly empower more comprehensive and personalised care.

Notwithstanding the advancements of these technologies, she emphasised the need for caution, especially when testing for diseases with non-specific genetic biomarkers, or interpreting pathogenic variants. Dr Chien summarised, “Even as we adopt advanced screening technologies like NGS to enhance test performance, we should concurrently work together to expand our knowledge of variants to support more robust interpretations, as well as grow our genetic counselling capabilities to better support affected families.”

Protecting Future Generations with Reproductive Carrier Screening

Building on Dr Chien’s sharing, Prof Delatycki outlined Australia’s corresponding journey in reproductive carrier screening, noting a similar growth trajectory in disease and population coverage over the years. He observed that the current state of NGS technology allows reproductive carrier screening to be performed on over 1,000 genes for most known autosomal and X-linked recessive genes, except for spinal muscular atrophy (SMA) and fragile X syndrome (FRAX) which require standalone tests.

In Australia, carrier screening for cystic fibrosis, spinal muscular atrophy and fragile X syndrome as well as haemoglobinopathies is funded by the government while expanded carrier screening is payable by patients.

Increasing demand for accessible carrier screening eventually led to the launch of the Mackenzie’s Mission research study in 2018. The three-year study, which concluded in 2022, screened a panel of 1,281 genes and standardised reporting for pathogenic or likely pathogenic variants and variant combinations that are expected to have a severe childhood onset presentation and/or where early intervention is shown to improve prognosis.

Presenting the findings of Mackenzie’s Mission, Prof Delatycki pointed out that over 82.8% of couples who took part in the screening and discovered an increased risk of genetic diseases made active decisions to avoid passing their condition to the next generation. They did so with Preimplantation Genetic Test for Monogenetic (PGT-M), Prenatal Diagnosis (PND) or choosing not to conceive children.

More significantly, findings from Mackenzie’s Mission suggest that the community shows a high level of acceptance towards expanded carrier screening—and that this model of carrier screening is clinically impactful and effective. Prof Delatycki concluded, “The data from Mackenzie’s Mission speaks for itself. Not only does the community generally find carrier screening acceptable, many would take it up if it were freely available. Furthermore, an organised national screening programme—akin to the bowel cancer screening programme—is highly cost effective.”

Ensuring Ethical Implementation and Practice in Genomic Screening

The science of genomic screening is rapidly advancing. However, comparatively less progress has been made in areas such as accessibility, equality, ethical approaches, and governance. Referencing current developments in genomic medicine and the prevailing understanding of medical ethics, Prof Thong emphasised the urgency of addressing gaps between them to ensure that the perceived benefits of genomic screening can be fully realised.

Using case examples of a one-year-old boy diagnosed with beta thalassaemia major, a two-year-old child with two gene variants of uncertain significance, and siblings with citrin deficiency, Prof Thong effectively demonstrated that while genomic medicine offers opportunities for intervention, varying clinical practices and standards can impede treatments—particularly in developing countries, where availability and affordability are unevenly distributed. Through the examples, he also raised the seldom-discussed issue of assent in genetic testing for minors.

Prof Thong advocated, “We are in an era where genomic medicine can shorten the diagnostic odyssey for rare diseases, offer new therapies, and devise preventive strategies for better health outcomes. To fully capture these gains, let’s collaborate at the public policy level to standardise ethical approaches by establishing evidence-based guidelines and policies that can be consistently adopted across all laboratories. In clinical settings, more healthcare practitioners must embrace the practice of genomic medicine. This may involve redistributing some of this work across healthcare systems so that genetics-trained specialists can better focus their efforts on complex cases.”

This is the second of a three-part PRECISE-IHCC Conference series. Themed “From Cohorts to Clinics: The New Landscape of Global Healthcare”, the Conference held from 21 to 23 August 2024 in Singapore covered 17 topics in precision medicine and sought to address challenges and opportunities in translating advances into tangible enhancements in patient care to reshape the landscape of modern healthcare.

If you missed the session, catch up on the conference video recording here: https://youtu.be/XI9W8Y8enbo?si=JHqm2fnx8Mot5ljh

For more post-conference resources, visit here.