Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies

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Sohail , M , Maier , R M , Ganna , A , Bloemendal , A , Martin , A R , Turchin , M C , Chiang , C W K , Hirschhorn , J , Daly , M J , Patterson , N , Neale , B , Mathieson , I , Reich , D & Sunyaev , S R 2019 , ' Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies ' , eLife , vol. 8 , 39702 . https://doi.org/10.7554/eLife.39702

Title: Polygenic adaptation on height is overestimated due to uncorrected stratification in genome-wide association studies
Author: Sohail, Mashaal; Maier, Robert M.; Ganna, Andrea; Bloemendal, Alex; Martin, Alicia R.; Turchin, Michael C.; Chiang, Charleston W. K.; Hirschhorn, Joel; Daly, Mark J.; Patterson, Nick; Neale, Benjamin; Mathieson, Iain; Reich, David; Sunyaev, Shamil R.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Massachusetts General Hospital
Date: 2019-03-21
Language: eng
Number of pages: 17
Belongs to series: eLife
ISSN: 2050-084X
URI: http://hdl.handle.net/10138/300784
Abstract: Genetic predictions of height differ among human populations and these differences have been interpreted as evidence of polygenic adaptation. These differences were first detected using SNPs genome-wide significantly associated with height, and shown to grow stronger when large numbers of sub-significant SNPs were included, leading to excitement about the prospect of analyzing large fractions of the genome to detect polygenic adaptation for multiple traits. Previous studies of height have been based on SNP effect size measurements in the GIANT Consortium meta-analysis. Here we repeat the analyses in the UK Biobank, a much more homogeneously designed study. We show that polygenic adaptation signals based on large numbers of SNPs below genome-wide significance are extremely sensitive to biases due to uncorrected population stratification. More generally, our results imply that typical constructions of polygenic scores are sensitive to population stratification and that population-level differences should be interpreted with caution. 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).
Subject: GENETIC RISK
POPULATION-STRUCTURE
SELECTION
DISEASE
PREDICTION
HISTORY
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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