Human Genetics Society of Australasia Position Statement: Use of Polygenic Scores in Clinical Practice and Population Health

Abstract

Considerable progress continues to be made with regards to the value and use of disease associated polygenic scores (PGS). PGS aim to capture a person’s genetic liability to a condition, disease, or a trait, combining information across many risk variants and incorporating their effect sizes. They are already available for clinicians and consumers to order in Australasia. However, debate is ongoing over the readiness of this information for integration into clinical practice and population health. This position statement provides the viewpoint of the Human Genetics Society of Australasia (HGSA) regarding the clinical application of disease-associated PGS in both individual patients and population health. The statement details how PGS are calculated, highlights their breadth of possible application, and examines their current challenges and limitations. We consider fundamental lessons from Mendelian genetics and their continuing relevance to PGS, while also acknowledging the distinct elements of PGS. Use of PGS in practice should be evidence based, and the evidence for the associated benefit, while rapidly emerging, remains limited. Given that clinicians and consumers can already order PGS, their current limitations and key issues warrant consideration. PGS can be developed for most complex conditions and traits and can be used across multiple clinical settings and for population health. The HGSA’s view is that further evaluation, including regulatory, implementation and health system evaluation are required before PGS can be routinely implemented in the Australasian healthcare system.

Future implications of polygenic risk scores for life insurance underwriting

“…Despite commercial availability, there are currently no best practice guidelines for developing and reporting PGS, and evidence for clinical utility is still emerging 15 , 16 , 32 . Several professional organizations have released position statements on the use of PGS in clinical practice, which commonly acknowledge the potential benefits of PGS, while urging for caution given the limited evidence for its clinical utility 49 – 51 . Statistical methods for calculating PGS are constantly being improved and new GWAS data is being generated.…”

Public Attitudes, Interests, and Concerns Regarding Polygenic Embryo Screening

“…However, with the advent of genome-wide association studies, polygenic scores have been developed for predicting physical health conditions (eg, coronary heart disease or type 1 diabetes), psychiatric health conditions (eg, schizophrenia or depression), behavioral traits (eg, educational attainment or extraversion), and physical traits (eg, height or skin color) . Although studies demonstrate that applying polygenic scores to embryos is practically feasible, the technology faces substantial limitations due to the correlational nature of polygenic scores and to their low predictive power, their variable performance across environments and populations, and the limited genetic diversity between sibling embryos . Beyond these limitations, PES has raised psychosocial concerns among clinicians, patients, genetic counselors, bioethicists, psychologists, and lawyers due to its potential impact on individuals and society at large .…”

“… 8 , 9 Although studies demonstrate that applying polygenic scores to embryos is practically feasible, 10 , 11 , 12 , 13 the technology faces substantial limitations due to the correlational nature of polygenic scores and to their low predictive power, their variable performance across environments and populations, and the limited genetic diversity between sibling embryos. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 Beyond these limitations, PES has raised psychosocial concerns among clinicians, patients, genetic counselors, bioethicists, psychologists, and lawyers due to its potential impact on individuals and society at large. 8 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 Despite these limitations and concerns, PES is already commercially available in the US and unregulated as to the types of polygenic outcomes that can be screened.…”