RT Journal Article
SR Electronic
T1 How robust are cross-population signatures of polygenic adaptation in humans?
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.13.200030
DO 10.1101/2020.07.13.200030
A1 Refoyo-Martínez, Alba
A1 Liu, Siyang
A1 Jørgensen, Anja Moltke
A1 Jin, Xin
A1 Albrechtsen, Anders
A1 Martin, Alicia R.
A1 Racimo, Fernando
YR 2020
UL http://biorxiv.org/content/early/2020/08/14/2020.07.13.200030.abstract
AB Over the past decade, summary statistics from genome-wide association studies (GWAS) have been used to detect and quantify polygenic adaptation in humans. Several studies have reported signatures of natural selection at sets of SNPs associated with complex traits, like height and body mass index. However, more recent studies suggest that some of these signals may be caused by biases from uncorrected population stratification in the GWAS data with which these tests are performed. Moreover, past studies have predominantly relied on SNP effect size estimates obtained from GWAS panels of European ancestries, which are known to be poor predictors of phenotypes in non-European populations. Here, we collated GWAS data from multiple anthropometric and metabolic traits that have been measured in more than one cohort around the world, including the UK Biobank, FINRISK, Chinese NIPT, Biobank Japan, APCDR and PAGE. We then evaluated how robust signals of polygenic adaptation are to the choice of GWAS cohort used to identify associated variants and their effect size estimates, while using the same panel to obtain population allele frequencies (The 1000 Genomes Project). We observe many discrepancies across tests performed on the same phenotype and find that association studies performed using multiple different cohorts, like meta-analyses, tend to produce scores with strong overdispersion across populations. This results in apparent signatures of polygenic adaptation which are not observed when using effect size estimates from biobank-based GWAS of homogeneous ancestries. Indeed, we were able to artificially create score overdispersion when taking the UK Biobank cohort and simulating a meta-analysis on multiple subsets of the cohort. This suggests that extreme caution should be taken in the execution and interpretation of future tests of polygenic adaptation based on population differentiation, especially when using summary statistics from GWAS meta-analyses.Competing Interest StatementThe authors have declared no competing interest.