PRECISION MEDICINE AND POLYGENIC RISK ๐ŸŽ—

“We’ve known for a long time that there are people out there at high risk for disease based just on their overall genetic variation.” - Dr. Sekar Kathiresan

๐Ÿงฌ Precision medicine aims to shape disease prevention, diagnosis, and treatment to individual characteristics, including genetics, environment, lifestyle, and other biological factors. Advances in genomics have made it possible to identify genetic variants associated with disease susceptibility and treatment response, supporting more individualized approaches to conditions such as cardiovascular disease, cancer, diabetes, infertility, and other complex disorders.

๐Ÿ”น Polygenic risk is an important component of precision medicine. Many common diseases arise from the combined effects of numerous genetic variants, each contributing a small amount to overall risk. A polygenic risk score (PRS) aggregates these effects to estimate an individual's inherited susceptibility to a particular disease or trait.

๐Ÿ”น PRSs may support earlier prevention and risk-based screening. Individuals with higher genetic susceptibility could potentially benefit from enhanced monitoring or earlier interventions, depending on the disease and supporting clinical evidence. However, a high PRS does not mean that disease is inevitable, and a low score does not eliminate risk. Disease outcomes reflect interactions among genetics, environment, lifestyle, age, and other biological factors.

๐Ÿ”น Integrating polygenic risk with clinical history, family history, laboratory measurements, and environmental factors may provide a more comprehensive assessment of disease risk. In some settings, genetic information may also contribute to treatment selection and prevention strategies.

➡️ Important limitations remain. PRS performance depends on the populations and genomic datasets used for development and validation. Many existing scores have been derived predominantly from European-ancestry datasets and may therefore show reduced transferability across other populations. Improving ancestral diversity in genomic research and validating PRSs across populations are essential for equitable clinical implementation.

⚠️ In an Oystershell, precision medicine and polygenic risk represent important developments in genomic healthcare. PRSs can contribute to understanding inherited susceptibility to complex diseases, but they should be interpreted as one component of a broader clinical smennot as definitive predictions of future health.

Abubakar Abubakar ✍️

• Khera AV, et al. Nature Genetics. 2018;50:1219-1224.

• Torkamani A, Wineinger NE, Topol EJ. Nature Reviews Genetics. 2018;19:581-590.

• Martin AR, et al. Nature Genetics. 2019;51:584-591.

• Polygenic Risk Score Task Force. Nature Medicine. 2021;27:1876-1884.

#PrecisionMedicine #PolygenicRisk #PolygenicRiskScores #Genomics #HumanGenetics #GenomicMedicine #DNA #RNA #GeneticCounseling #CRISPR #NGS #PGT #IVF #ART ⚕



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