Half a century later and we're back where we started: How the problem of locality turned in to the problem of portability

Abstract

In the 1970s, Lewontin sparked a debate about a problem of locality, by making the case that any given heritability estimate is local to the original population and environment studied, and could not be generalized to other populations and environments. Nearly 50 years later, a new problem of portability has emerged: the predictive accuracy of polygenic scores diminishes when applied to populations whose characteristics are different from the original population sample. This paper briefly reviews the nature of each problem and analyzes their similarities and differences in three areas: 1) conceptual underpinnings, 2) causal explanations, and 3) practical, social, and political implications. Although conceptually and methodologically different from the problem of locality in important respects, the problem of portability facing contemporary genomics today should come as no surprise, as it is an inevitable outcome of the kinds of problematic inferences detailed by Lewontin nearly half a century ago.