Abstract
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 20th 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.
Highlights
This study evaluates changes in polygenic penetrance—defined as the association between a polygenic score (PGS) and its associated phenotype—across recent birth cohorts in the United States
We exploit this opportunity by asking whether the associations between PGS and several phenotypes have changed over the course of the 20th century in the U.S Because the economic, social, and physical environments underwent dramatic changes during this period, it is likely that the association between a PGS and its related phenotype has evolved as a consequence[2]
Our data are from the 2012 wave of the Health and Retirement Study (HRS), and allowed us to observe the consistency of PGS-phenotype correlations across birth cohorts in the mid-20th century among U.S adults
Summary
This study evaluates changes in polygenic penetrance—defined as the association between a polygenic score (PGS) and its associated phenotype—across recent birth cohorts in the United States. Studies which employ sibling and twin comparisons and candidate gene studies show the same pattern of increasing genetic penetrance with respect to tobacco use among recent cohorts[16,17] These results suggest that as the dangers of tobacco use were publicized in the latter half of the 20th century, the underlying genotype signifying a greater propensity to smoke exerted a more pronounced influence on behavior. Twin-based models of the heritability of education appear to show an increasing effect of genotype over a similar time period[20] We expand on this literature by focusing on a wider breadth of phenotypes and employ polygenic scores based on millions of SNPs rather than individual markers in identifying historical shifts in genetic expression
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