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Reduced signal for polygenic adaptation of height in UK Biobank

View ORCID ProfileJeremy J Berg, View ORCID ProfileArbel Harpak, View ORCID ProfileNicholas Sinnott-Armstrong, View ORCID ProfileAnja Moltke Joergensen, View ORCID ProfileHakhamanesh Mostafavi, View ORCID ProfileYair Field, Evan A Boyle, View ORCID ProfileXinjun Zhang, View ORCID ProfileFernando Racimo, View ORCID ProfileJonathan K Pritchard, View ORCID ProfileGraham Coop
doi: https://doi.org/10.1101/354951
Jeremy J Berg
Columbia University;
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  • For correspondence: jeremy.jackson.berg@gmail.com
Arbel Harpak
Columbia University;
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Nicholas Sinnott-Armstrong
Stanford University;
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Anja Moltke Joergensen
University of Copenhagen;
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Hakhamanesh Mostafavi
Columbia University;
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Yair Field
Stanford University;
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Evan A Boyle
Stanford University;
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Xinjun Zhang
University of California, Davis
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Fernando Racimo
University of Copenhagen;
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Jonathan K Pritchard
Stanford University;
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Graham Coop
University of California, Davis
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 25, 2018.
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Reduced signal for polygenic adaptation of height in UK Biobank
Jeremy J Berg, Arbel Harpak, Nicholas Sinnott-Armstrong, Anja Moltke Joergensen, Hakhamanesh Mostafavi, Yair Field, Evan A Boyle, Xinjun Zhang, Fernando Racimo, Jonathan K Pritchard, Graham Coop
bioRxiv 354951; doi: https://doi.org/10.1101/354951
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Reduced signal for polygenic adaptation of height in UK Biobank
Jeremy J Berg, Arbel Harpak, Nicholas Sinnott-Armstrong, Anja Moltke Joergensen, Hakhamanesh Mostafavi, Yair Field, Evan A Boyle, Xinjun Zhang, Fernando Racimo, Jonathan K Pritchard, Graham Coop
bioRxiv 354951; doi: https://doi.org/10.1101/354951

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