Journal Article

Reduced signal for polygenic adaptation of height in UK Biobank

Berg, Jeremy J, Harpak, Arbel, Field, Yair, Mostafavi, Hakhamanesh, Coop, Graham, Joergensen, Anja Moltke, Pritchard, Jonathan K, Racimo, Fernando, Boyle, Evan August, Zhang, Xinjun, Sinnott-Armstrong, Nasa

2019

Overview

Several recent papers have reported strong signals of selection on European polygenic height scores. These analyses used height effect estimates from the GIANT consortium and replication studies. Here, we describe a new analysis based on the the UK Biobank (UKB), a large, independent dataset. We find that the signals of selection using UKB effect estimates are strongly attenuated or absent. We also provide evidence that previous analyses were confounded by population stratification. Therefore, the conclusion of strong polygenic adaptation now lacks support. Moreover, these discrepancies highlight (1) that methods for correcting for population stratification in GWAS may not always be sufficient for polygenic trait analyses, and (2) that claims of differences in polygenic scores between populations should be treated with caution until these issues are better understood. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter ).

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Adaptation / Adaptation, Biological / Biology / Biostatistics / Body Height / Consortia / Databases, Factual / Datasets / Estimates / Europe / Evolutionary Biology / Genetics and Genomics / GWAS / Humans / Multifactorial Inheritance / natural selection / polygenic adaptation / Polygenic inheritance / Population / population genetics / population structure / quantitative genetics / Research Communication / Selection, Genetic / Standard deviation