Why are Polygenic Risk Scores so Different from Other Predictive Biomarkers?

Polygenic Risk Score (PRS) is not a single biomarker tied to one gene or a clear biological mechanism. Instead, it's a risk signature, a calculation based on many small genetic changes across the genome, each contributing a little to a person’s overall disease risk.

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When interpreted in the right clinical context - alongside personal and family history, other clinical findings - PRS can help guide specific decisions

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Understanding Polygenic Risks

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​Fixed from Birth 

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• Polygenic risk is based on common genetic variants (SNPs) inherited at birth. This risk score does not change over time. it's part of a person's DNA from the start.

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Complements Monogenic Testing by Capturing the "Missing Risk"

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• Traditional genetic testing targets rare, high-impact (penetrance) mutations (e.g., BRCA1/2). However, most individuals at elevated disease risk do not carry these mutations.

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• PRS captures the combined impact of up to a million common variants, that can explain additional risk that monogenic testing alone misses.​

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For Patients Without a Family History 

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• PRS does not follow classic inheritance models (e.g. dominant or recessive).

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• Risk may not track predictably within families, as it reflects polygenic architecture rather than single-gene transmission. As a result, individuals with significant polygenic risk may not have a notable family history or affected first-degree relatives.​​

Interpretation of PRS in the Clinical Context - An Example

Prostate Biopsy

For men with moderately-elevated PSA, prostate cancer polygenic risk scores may support prostate biopsy decisions or additional follow up. 

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​Binary Decision Aid

• In a major study (~6,400 UK men, aged 55–69) (New England Journal of Medicine, 2025) (1, 2), men with high PRS had a much higher chance of having prostate cancer (40% prostate cancer detection rate).

• Within this group, 55% were confirmed to have clinically significant cancers, and many of which were missed by PSA + MRI alone.

• Similar conclusions were reported in multiple studies across a number of ethnicities (3-5). In fact, evidence has been accumulated over the last decade. 

• Clinical Utility: If you have a moderately-elevated PSA, with other clinical tests showing ambigious results (like an inconclusive Digital Rectal Exam), your physician may include a PRS test result to determine biopsy necessity or referral for a MRI screening.  

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To learn more about our integrated monogenic and polygenic prostate cancer testing, please see our Test Overview for Physicians.

A Full-Genome PRS Helps Doctors Better

Polygenic Risk Scores (PRS) built from whole-genome SNP data are more accurate than those based on limited SNP arrays or only high-impact variants.

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This is supported by multiple studies from leading institutions. The reason is simple:

• Full-Genome PRS captures the cumulative effect of up to a million small genetic differences across the entire genome, including those that individually have modest effects but, in aggregate, significantly improve risk prediction (6).

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• In contrast, SNP arrays or panels that focus only on a few high-impact variants miss much of this polygenic background, leading to lower predictive performance.

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• The result:

  • Full-genome PRS offers greater accuracy, better risk stratification, and more clinically meaningful insights, particularly when used alongside clinical factors and family history.

Accurate Ancestry Matters in Polygenic Risk Scoring

Self-Reported Ancestry Is Often Inaccurate

• Many individuals base their ancestry on recent family history, like saying “I’m European” because their parents or grandparents are. But genetically, they may also have Asian, African, or other roots they’re not aware of, especially if they have mixed ancestry.

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Inaccurate Ancestry = Wrong Risk Score

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• Polygenic Risk Scores (PRS) are sensitive to ancestral background - to estimate your chances of getting certain diseases based on your genes. But they only work well if the ancestry used is accurate. If the wrong background is used, the risk score could be misleading, either too high or too low. 

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• This is especially problematic for individuals of mixed ancestry, where standard PRS tools may not account for their unique genetic composition, leading to clinically unhelpful guidance.

Galatea’s Ancestry-Adjusted PRS Approach

• At Galatea, we take a meticulous approach to ancestry determination before calculating PRS.

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• We analyze your full DNA (genomic data) to find out your real genetic mix. Then we use that information to calculate a risk score that fits you, even if you come from a mix of backgrounds.

• This makes the results more accurate and useful for making health decisions.