polygenic adaptation

Turchin MC, Chiang CWK, Palmer CD, Sankararaman S, Reich D, GIANT Consortium & Hirschhorn JN 2012 Evidence of widespread selection on standing variation in Europe at height-associated SNPs. Nat Genet 44:1015-1019.

  • frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans
  • the systematic frequency differences are consistent with the presence of widespread weak selection (selection coefficients ~10−3–10−5 per allele) rather than genetic drift alone
  • we have implemented an approach that combines evidence for selection across many loci
  • for the most strongly associated ~1,400 SNPs, the estimated effects of the Northern-predominant alleles on height are indistinguishable between the sibship-based test and the GIANT data set
  • to ensure that our conclusions are not confounded by stratification, we therefore focus our subsequent analyses on this set of ~1,400 independent SNPs
  • the allele frequency of these ~1,400 height-increasing alleles is significantly higher in Northern than in Southern Europeans
  • the frequencies in a Central-European population (Swiss-French from POPRES) fall between those of the Northern- and Southern-European POPRES populations
  • the data indicate a small but systematic increase over time in the frequency of height-increasing alleles in Northern Europe and/or a decrease in frequency in Southern Europe
  • we asked whether this systematic change in frequency of height-increasing alleles can be explained by genetic drift or is more consistent with a model that also incorporates selection
  • models incorporating both selection and drift were more consistent with the data than models of drift alone
  • given typical effect sizes of height-associated variants, which are generally ≤ 10−2–10−3 s.d. (1 s.d. ≈ 6.5 cm), we estimate that, in a model where selection is proportional to effect size, the typical selective pressure on individual height-associated variants would be ~10−3–10−5 per allele per generation
  • by aggregating evidence of directionally consistent intra-European frequency differences over many individual height-increasing alleles, none of which has a clear signal of selection on its own, we observed a combined signature of widespread weak selection
  • we were not able to determine whether this differential weak selection (either positive or negative) favored increased height in Northern Europe, decreased height in Southern Europe or both
  • it is also possible that selection is not acting on height per se but on a phenotype closely correlated with height or a combination of phenotypes that includes height