Alison R. Barton

Abstract Causal disease effect sizes of proximal single-nucleotide polymorphisms (SNPs) are widely assumed to be independent but could be correlated. Here we introduce a new method, linkage disequilibrium SNP-pair effect correlation regression (LDSPEC), to estimate the correlation of causal disease effect sizes of derived alleles between proximal SNPs; LDSPEC produced robust estimates in simulations.

Abstract Ancient DNA has transformed our understanding of population history1, but its potential to reveal as much about human evolutionary biology has not been realized because of limited sample sizes and the difficulty of distinguishing sustained rises in allele frequency increasing fitness—directional selection—from shifts due to migrations, population structure, or non-adaptive purifying or stabilizing selection2,3,4,5,6,7.

arising from: J. Klunk et al. Nature https://doi.org/10.1038/s41586-022-05349-x (2022). Klunk et al.1 analysed ancient DNA from before, during and after the Black Death, and claimed that large allele frequency changes at immune genes in aggregate, and at four specific variants, reflected natural selection. These claims are unsupported for four reasons.