From individual to population disease risk: population-averaged polygenic risk scores

Polygenic risk score (PRS) is a tool to quantify the susceptibility of an individual to a disease by using the results of individual gene sequencing to calculate the cumulative effect of genetic susceptibility loci. In this study, we extend the individual-based PRS to the population-based mean polygenic risk score (PMPRS), Further more, we constructed the risk score ratio (RSR) for etiology exploration. In the case study, we applied above method to explore the relationship between study six inflammatory factors and coronary heart disease (CHD). Our studies have shown that tumor necrosis factor-α (TNF-α) and procalcitonin (PCT) are potential risk factors for CHD. The RSR corresponding to TNF-α is 4.97 (prediction interval: 2.99, 10.548); the RSR corresponding to PCT is 21.87 (prediction interval: 2.29, 232.28), and controlling the levels of TNF-α and PCT can be used as a primary preventive measure to reduce the occurrence of coronary heart disease.