🧬 A beautiful @NatureGenet paper on how to handle polygenic risk more carefully in family-based data. The core idea is to compare a child not with random people, but with the genetic set they could have inherited from their own parents. This better protects against population stratification, geography, social structure, and assortative mating. The authors introduce PGS-TRI, a method that estimates not only the direct effect of the child’s PGS, but also gene–environment interactions and asymmetric indirect effects of maternal and paternal genetics. For the educational-attainment simulations, the authors used UK Biobank to create a realistic confounded setting with geography, BMI, and assortative mating. Standard regression became biased, while PGS-TRI stayed well calibrated. In real autism trios, the method found a direct polygenic effect close to previous case–control estimates. It also showed that the score’s effect declines smoothly with genetic distance from the European training population. nature.com/articles/s41588-0… #Trio #PopulationStratification #Autism #PRS #PGS