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This study evaluates changes in genetic penetrance—defined as the association between an additive polygenic score and its associated phenotype—across birth cohorts. Situating our analysis within recent historical trends in the U.S., we show that, while height and BMI show increasing genotypic penetrance over the course of 20 th  Century, education and heart disease show declining genotypic effects. Meanwhile, we find genotypic penetrance to be historically stable with respect to depression. Our findings help inform our understanding of how the genetic and environmental landscape of American society has changed over the past century, and have implications for research which models gene-environment (GxE) interactions, as well as polygenic score calculations in consortia studies that include multiple birth cohorts.

Changing Polygenic Penetrance on Phenotypes in the 20th Century Among Adults in the US Population