Interpreting polygenic scores, polygenic adaptation, and human phenotypic differences

Noah A Rosenberg; Michael D Edge; Jonathan K Pritchard; Marcus W Feldman

doi:10.1093/emph/eoy036

Interpreting polygenic scores, polygenic adaptation, and human phenotypic differences

Evol Med Public Health. 2018 Dec 27;2019(1):26-34. doi: 10.1093/emph/eoy036. eCollection 2019.

Authors

Noah A Rosenberg¹, Michael D Edge², Jonathan K Pritchard^{1

3

4}, Marcus W Feldman¹

Affiliations

¹ Department of Biology, Stanford University, Stanford, CA, USA.
² Department of Evolution and Ecology, University of California, Davis, CA, USA.
³ Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
⁴ Department of Genetics, Stanford University, Stanford, CA, USA.

Abstract

Recent analyses of polygenic scores have opened new discussions concerning the genetic basis and evolutionary significance of differences among populations in distributions of phenotypes. Here, we highlight limitations in research on polygenic scores, polygenic adaptation and population differences. We show how genetic contributions to traits, as estimated by polygenic scores, combine with environmental contributions so that differences among populations in trait distributions need not reflect corresponding differences in genetic propensity. Under a null model in which phenotypes are selectively neutral, genetic propensity differences contributing to phenotypic differences among populations are predicted to be small. We illustrate this null hypothesis in relation to health disparities between African Americans and European Americans, discussing alternative hypotheses with selective and environmental effects. Close attention to the limitations of research on polygenic phenomena is important for the interpretation of their relationship to human population differences.

Keywords: adaptation; health disparities; human variation; polygenic scores; population genetics.

Publication types

Review

Abstract

Publication types

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