The lifetime risk of developing a chronic condition, such as cancer or heart disease, is determined by several factors, including genetics, environment, and lifestyle. Genetic determinants may be either rare gene variants (mutations) that confer a high risk within the same family or common variants that may combine to confer a higher risk than that found in the general population. Polygenic risk scores (PRS) provide a measure of the genetic risk of developing these diseases, by measuring the combined effect of a large number of common variants (termed single nucleotide polymorphisms, or SNPs) that have been associated with increased risk for a particular disease in your population. Your PRS will be different for each specific disease: for example, you might be at low genetic risk for breast cancer, but at increased genetic risk for heart disease. PRS scores for a number of conditions are available; to obtain further information about a PRS test for a specific condition, select a test of interest on this link.
PRS testing is carried out on a buccal specimen (mouth swab). DNA from the swab will be extracted and analyzed by next-generation sequencing or microarrays to yield a list of SNPs. The SNPs found in your sample will be compared to those in the general population, by means of specialized software developed by our partners, Allelica, Inc., and Antegenes, to generate the polygenic risk score. A high PRS equates to your genes giving you a comparatively higher than average risk compared to someone of your age and ethnicity. Having a high genetic risk does not mean that the disease will definitely develop, as there are numerous additional lifestyle and physiological factors that contribute to modifying the absolute risk. This is why, at The BioArte, we provide a tailor-made lifestyle report together with the PRS score. To do this, we will also collect some information about your lifestyle and environmental risk factors by means of an online questionnaire. Filling in this questionnaire to the best of your knowledge will help us provide you with the best advice.
Frequently Asked Questions
PRS scores are intended to provide a quantitative assessment of an individual’s future risk of disease conferred by their genes, to help healthcare professionals in providing the best lifestyle advice. They are not intended for the diagnosis of any disease or health condition.
You should choose this test if you are healthy and would like to estimate your genetic risk for future chronic diseases and receive personalized advice to mitigate this risk by modifying your lifestyle.
This test should only be performed on consenting adults and is not intended to be used, and has no utility, to assess risk in any of the following situations: children under the age of 18; in vitro fertilization-embryo selection; carrier screening for family planning.
- The “Results & Interpretation” sections will contain your polygenic risk score as a numerical result, together with its translation into relative risk, e.g. Your 10-year risk of developing cancer is 1.9 x that of the general population
- The “Recommendations” section will contain lifestyle advice tailor-made to you, based on the lifestyle factors from the questionnaire and the PRS result.
The polygenic risk score is expressed as standard deviations from the average PRS (z-score), so a PRS value of 1.3 means that the individual’s PRS is 1.3 standard deviations higher than the average person, who would get a PRS score of 0. The risk calculations are based on a hazard ratio per standard deviation (HRsd) estimate derived from a Cox proportional hazards model estimated from international biobank data.
To arrive at the relative fold-change risk (i.e. X x risk in the general population), we first calculate the absolute risk for the patient and a person with the average PRS of the same age and nationality. This calculation incorporates country-specific background information – age-specific all-cause mortality (i.e. death by any other cause than the condition), the incidence of the condition, and the mortality from the condition. These risks are integrated over a 10-year time horizon into 10-year absolute risk estimates using the methods of survival analysis. For more information about this, see Choudhury et al. (Pal Choudhury P, Maas P, Wilcox A, Wheeler W, Brook M, Check D, et al. PloS one. 2020;15(2):e0228198). Finally, the ratio of these two absolute risks (risk for the patient/risk for an average person of the same age and nationality) is given as the relative risk.
PRS scores are not intended for the diagnosis of any disease or health condition. An elevated risk estimated by the PRS does not mean that the individual will develop the condition during their lifetime, and a moderate or low-risk score does not mean that the individual will not develop the condition. Depending on the condition, the PRS analyses take into account a range of tens to millions of common genetic variants that have been robustly associated with the disease of interest. However, there may still be additional, as yet unidentified, genetic variants involved in genetic risk. In addition, this test does not take into account either known or unknown pathogenic or likely pathogenic variants in known disease susceptibility genes. These may be present but unidentified and may additionally contribute to an individual’s genetic risk of developing a disease.