Preimplantation Genetic Testing for Polygenic disorders (PGT-P) offers prospective parents using in vitro fertilization (IVF) the ability to assess an embryo’s inherited risk for common, complex diseases. This technology departs from earlier genetic tests focused on structural chromosome problems or single-gene mutations. PGT-P analyzes the entire genome of an embryo to estimate the likelihood of developing conditions influenced by many different genes working together. Its emergence shifts the focus of embryo screening from identifying a specific diagnosis to estimating a probabilistic health risk for conditions that typically manifest in adulthood.
Defining Polygenic Risk Testing
Polygenic Risk Testing (PGT-P) is built on the understanding that most common human diseases are polygenic, involving the cumulative effect of many genes rather than a single genetic flaw. These conditions are also multifactorial because their development is shaped by the interplay between inherited genetic risk and non-genetic factors, such as diet, lifestyle, and environment. This distinguishes PGT-P from established Preimplantation Genetic Testing for monogenic disorders (PGT-M), which screens for conditions caused by a single, highly penetrant gene mutation.
Unlike PGT-M, which searches for a clear “yes/no” presence of a mutation (e.g., cystic fibrosis), PGT-P examines thousands of small genetic variations across the embryo’s genome. These variations, called single nucleotide polymorphisms (SNPs), each contribute a minute amount to the overall risk. When hundreds or thousands of risk-associated SNPs are considered together, their combined impact significantly influences the probability of developing a disease. PGT-P aims to identify embryos with the lowest overall genetic predisposition to specified complex conditions.
How Polygenic Risk Scores Are Calculated
The core of PGT-P is the calculation of a Polygenic Risk Score (PRS), a numerical estimate of an embryo’s genetic susceptibility to a particular trait or disease. This score is derived from vast genomic databases generated by Genome-Wide Association Studies (GWAS). GWAS compare the genomes of people with a specific disease to those without it to identify SNPs that occur more frequently in the affected group.
The calculation involves a weighted summation of an embryo’s genetic variants across its entire genome. The PRS assigns a specific weight to each identified SNP based on its measured contribution to disease risk, as determined by the GWAS data. This weighting ensures that variants with a larger impact are given more consideration. The resulting PRS is an aggregated figure that ranks the embryo’s genetic risk relative to a general population, often referred to as an Embryo Health Score (EHS) that prioritizes embryos with the lowest projected risk.
This methodology introduces complexity because the identified SNPs often “tag” genetic regions located nearby, rather than being the direct, causal mutation—a phenomenon called linkage disequilibrium. This reliance on statistical association, rather than direct biological mechanism, introduces uncertainty into the risk estimate. Furthermore, the score’s accuracy depends heavily on the quality and diversity of the underlying GWAS data, which historically has been primarily collected from populations of European descent.
Conditions Screened and Current Limitations
PGT-P is currently marketed for assessing risk for a variety of common, adult-onset conditions.
Conditions Screened
These conditions include:
Heart disease and coronary artery disease
Type 1 and Type 2 diabetes
Certain forms of cancer (e.g., breast, prostate, and testicular cancer)
Neurological conditions like schizophrenia
Non-medical traits such as adult height
The goal is to select an embryo predicted to fall into the lower percentiles of risk for these conditions compared to the general population.
Limitations of Prediction
A central limitation of PGT-P is that it predicts risk—a probability—rather than a certain diagnosis. A low PRS does not guarantee a disease-free life, nor does a high PRS mean the condition is inevitable, because the score only captures the genetic component of a complex, multifactorial disease. Non-genetic factors, such as diet, exercise, and environment, play a substantial role in whether a person ultimately develops the condition.
The predictive power of PGT-P is also constrained by ancestral bias in existing genomic databases. For individuals of non-European ancestry, the PRS derived from predominantly European data may be less accurate and less clinically useful. When multiple conditions are screened simultaneously, an embryo may show a low risk for one disease but an elevated risk for another. This scenario complicates the decision-making process for prospective parents, who must weigh conflicting risk predictions.
Ethical and Societal Implications
The clinical availability of PGT-P has generated significant ethical and societal debate centered on access, equity, and the definition of a desirable child. Since PGT-P is a costly procedure performed with IVF, its expense creates a substantial barrier to entry. This means only individuals with significant financial resources can utilize the technology, raising concerns about exacerbating existing societal inequalities and stratifying health outcomes based on wealth.
The technology also fuels concerns about selecting non-disease traits, often called the “designer baby” debate. Screening for traits like height or cognitive ability blurs the line between preventing disease and selecting for enhancement. Furthermore, ranking embryos by risk score and potentially discarding those with a higher predicted risk raises philosophical questions about the moral status of the embryo. The focus on genetic solutions also risks diverting attention from addressing the environmental and social determinants that contribute significantly to complex diseases.