Reduced signal for polygenic adaptation of height in UK Biobank

Author:

Berg Jeremy J1ORCID,Harpak Arbel12ORCID,Sinnott-Armstrong Nasa3ORCID,Joergensen Anja Moltke4,Mostafavi Hakhamanesh1ORCID,Field Yair3,Boyle Evan August3ORCID,Zhang Xinjun5ORCID,Racimo Fernando4ORCID,Pritchard Jonathan K26ORCID,Coop Graham78ORCID

Affiliation:

1. Department of Biological Sciences, Columbia University, New York, United States

2. Department of Biology, Stanford University, Stanford, United States

3. Department of Genetics, Stanford University, Stanford, United States

4. Lundbeck GeoGenetics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark

5. Department of Anthropology, University of California, Davis, Davis, United States

6. Howard Hughes Medical Institute, Stanford University, Stanford, United States

7. Center for Population Biology, University of California, Davis, Davis, United States

8. Department of Evolution and Ecology, University of California, Davis, Davis, United States

Abstract

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 (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

Funder

National Institutes of Health

Stanford Center for Computational, Evolutionary and Human Genomics

U.S. Department of Defense

Stanford University

Villum Fonden

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference50 articles.

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