RT Journal Article
SR Electronic
T1 Reduced signal for polygenic adaptation of height in UK Biobank
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 354951
DO 10.1101/354951
A1 Jeremy J. Berg
A1 Arbel Harpak
A1 Nasa Sinnott-Armstrong
A1 Anja Moltke Jørgensen
A1 Hakhamanesh Mostafavi
A1 Yair Field
A1 Evan A Boyle
A1 Xinjun Zhang
A1 Fernando Racimo
A1 Jonathan K Pritchard
A1 Graham Coop
YR 2018
UL http://biorxiv.org/content/early/2018/06/27/354951.abstract
AB There is considerable variation in average height across European populations, with individuals in the northwest being taller, on average, than those in the southeast. During the past six years, a series of papers reported that polygenic scores for height also show a north to south gradient, and that this cline results from natural selection. These polygenic analyses relied on external estimates of SNP effects on height, taken from the GIANT consortium and from smaller replication studies. Here, we describe a new analysis based on SNP effect estimates from a large independent data set, the UK Biobank (UKB). We find that the signals of selection using UKB effect-size estimates for height are strongly attenuated, though not entirely absent. Because multiple prior lines of evidence provided independent support for directional selection on height, there is no single simple explanation for all the discrepancies. Nonetheless, our current view is that previous analyses were likely confounded by population stratification and so the conclusion of strong polygenic adaptation in Europe now lacks clear support. Moreover, these discrepancies highlight (1) that current methods for correcting for population structure in GWAS may not always be sufficient for polygenic trait analyses, and (2) that claims of polygenic differences between populations should be treated with caution until these issues are better understood.