PRS
PGS are biomarkers, i.e., predictors of risk of diseases
PGS can be measured at any time during life (e.g., birth)
• Remain the same thru life because DNA is the same
• Update if GWAS discovery or PGS method change
PGS are not diagnostic genetic tests*
• Genetic risk only account for part of risk
• PGS only account for part of the genetic risk
• PGS will improve in accuracy as WAS discovery sample size increase
For an individual the prediction of error of a PGS is high, but the set of individuals with high PGS is significantly enriched for those who go on to get disease*
• Useful for risk stratification
PGS can be included in risk predictors that include other risk factors*
• Most non-genetic risk factors change with age
People without family history of a common disease could have high PGS
• PGS will vary between children of the same parents reflecting segregation variance
People with family history of a common disease may or may not have high PGS
• PGS captures only part of the genetic contribution to risk and so the relationship between PGS and family history will vary between families
PGS can have clinical utility without knowledge of causal risk variants
Common causal risk variants are ancient and shared across ancestries, transferability of PGS is improved if causal variants are identified and selected for use in the PGS.
clinical utility
• Disease risk prediction
• Improving and refining diagnoses
• Slowing disease progression & recurrence
• Improving population screening
• Prompting risk-reducing behaviours
• Improving cost and efficiency of trials
combine monogenetic with polygenetic
risk of PRS
• ‘False positive’ results
• Failure to convey uncertainty (false genetic determinism)
• Biases of representation (e.g. demographics)
• Healthcare professionals
• Communication of PGS results
• Psychosocial effects (e.g. anxiety, depression)
• Racists
• Embryo selection