bioRxiv (Cold Spring Harbor Laboratory) · 2018 · 61 citations · 44 references
Life SciencesBiostatisticsGeneticsHuman GeneticsPopulation GeneticsStatistical GeneticsCausal Inference In GeneticsGenome-wide Association StudiesHeritabilityPopulation GenomicsPopulation StratificationQuantitative Trait AnalysisEffect SizeGenetic Replication StudiesPolygenic AdaptationPolygenic Trait AnalysisPopulation Stratification AdjustmentPopulation Stratification CorrectionReplication StudiesSignals
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-size estimates for height 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.
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