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AncestryDNA® Learning Hub

AncestryDNA® Learning Hub

Polygenic Risk Score

Have you ever wondered how your DNA influences traits like eye color or hair color, or things like whether you remember dreams, prefer mornings or nights, or take risks? Is each trait determined by a single gene? Some of the 2022 AncestryDNA® traits reports actually look at thousands of genes to make a prediction about a single trait--like risk taking--using a tool called a polygenic risk score. (And some of the traits reports for 2023 will do so as well.)

What Is a Polygenic Risk Score?

A polygenic risk score (PRS) is a statistical tool scientists use to look at hundreds or thousands of genetic variants in a person's DNA. This tool can help predict your level of risk for a disease or the chances that you will inherit a certain trait. Genetic traits can be related to your appearance, physical fitness, sensory or nutrient sensitivity, behavior, and even personality.

When Were Polygenic Risk Scores Developed?

The concept of a PRS was first proposed as a method to improve traits in commercial crops and animals in a 2001 paper--before genotyping of genome-wide variants was even possible. A few years later, the geneticist Naomi Wray and her colleagues demonstrated that a person's genetic risk to a disease could be predicted by using thousands of genetic variants across the genome, each with only a small effect on the overall disease risk.

How Else Are Polygenic Risk Scores Used?

In the decades since the concept was first explored, polygenic risk scores have been widely researched and developed. Today, PRS can also be used to predict a person's predisposition to complex traits like:

Building a Polygenic Risk Score for Genetic Traits

In order to create polygenic risk scores, AncestryDNA® researchers, for example, rely on large genetic datasets gathered from DNA test results people have volunteered to share. They then look at the connections between individuals' phenotype and genotype information. Other researchers may rely on biobanks, which store the genetic information connected to health and traits information for thousands of consenting participants.

A PRS is most useful when the trait has a strong genetic component, like introversion or extroversion. If the heritability--how much variation in the trait is determined by genetic variation--is low, then there may be a greater discrepancy between what your DNA predicts and what your trait actually is. Though, even traits with high heritability, such as facial hair thickness, are strongly influenced by non-genetic factors like grooming habits.

What Role Does a Genome-Wide Association Study Play?

A genome-wide association study (GWAS) uses large DNA datasets and biobanks to provide the foundation for polygenic risk scores.

More specifically, a GWAS allows researchers to test and analyze statistical associations between genetic variants and different traits, like risk-taking behavior.

The GWAS also indicates the importance of each genetic variant in predicting that trait. Some variants may have a very small effect on a trait, but others could have a bigger impact. This is why researchers combine information from so many genetic variants to make a risk prediction. AncestryDNA® scientists, for example, used more than 10,000 genetic variants associated with introversion and extroversion to build a PRS model for predicting the trait.

However, not all large datasets reflect the genetic diversity of different global populations. Unfortunately, this can impact the accuracy of the results. It really depends on who participates in DNA studies--more diverse contributors translates into more accurate results for all.

Polygenic Risk Scores Compare Your DNA to Others

Keep in mind that a PRS can only provide a relative probability--how your chances for a trait, like remembering dreams, compares to others with a different genetic makeup. Here's a simplified look at how it works:

  • A PRS calculates the genetic scores for a group of individuals.
  • It then creates a stratification of those people based on their polygenic scores--meaning who is more likely to have a certain trait and who is less likely.
  • Each individual person's polygenic score is then assigned a place on a bell curve distribution.

Importantly, the PRS doesn't provide a baseline or absolute probability for the trait. Often, large differences in relative probability do not correspond to a large difference in absolute probability.

Genetics and Other Contributing Factors

While a PRS looks at a lot of genetic information to make a prediction about a trait, there's a lot of non-genetic information it doesn't consider. It doesn't consider environmental factors (like access to nutritious food) , life choices (like choosing to work a night shift), and random chance. But all of these can impact whether you do or don't have a trait, regardless of the chances predicted from your genetics.

So what does your DNA indicate? An AncestryDNA® Traits test can tell you whether you're more or less likely to be an introvert or extrovert, to have the sprinter gene, or if your aversion to cilantro is based in genetics.

 

References

Duncan, L., H. Shen, B. Gelaye, et al. "Analysis of polygenic risk score usage and performance in diverse human populations." Nature Communications, 2019. https://doi.org/10.1038/s41467-019-11112-0.

Meuwissen, T. H. E., B. J. Hayes, and M. E. Goddard. "Prediction of Total Genetic Value Using Genome-Wide Dense Marker Maps." Genetics, April 1, 2001. https://doi.org/10.1093/genetics/157.4.1819.

Wray, Naomi R., Michael E. Goddard, and Peter M. Visscher. "Prediction of individual genetic risk to disease from genome-wide association studies." Genome Research, 2007. https://genome.cshlp.org/content/17/10/1520.

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