PuSH - Publication Server of Helmholtz Zentrum München: Evidence of widespread selection on standing variation in Europe at height-associated SNPs.

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Turchin, M.C.* ; Chiang, C.W.* ; Palmer, C.D.* ; Sankararaman, S.* ; Reich, D.* ; GIANT Consortium (Heid, I.M. ; Thiering, E. ; Gieger, C. ; Grallert, H. ; Heinrich, J. ; Illig, T. ; Peters, A. ; Wichmann, H.-E.) ; Hirschhorn, J.N.*

Evidence of widespread selection on standing variation in Europe at height-associated SNPs.

Nat. Genet. 44, 1015-1019 (2012)

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Strong signatures of positive selection at newly arising genetic variants are well documented in humans(1-8), but this form of selection may not be widespread in recent human evolution(9). Because many human traits are highly polygenic and partly determined by common, ancient genetic variation, an alternative model for rapid genetic adaptation has been proposed: weak selection acting on many pre-existing (standing) genetic variants, or polygenic adaptation(10-12). By studying height, a classic polygenic trait, we demonstrate the first human signature of widespread selection on standing variation. We show that frequencies of alleles associated with increased height, both at known loci and genome wide, are systematically elevated in Northern Europeans compared with Southern Europeans (P < 4.3 × 10(-4)). This pattern mirrors intra-European height differences and is not confounded by ancestry or other ascertainment biases. 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 (P < 10(-15)).

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