RT Journal Article SR Electronic T1 Detecting Long-term Balancing Selection using Allele Frequency Correlation JF bioRxiv FD Cold Spring Harbor Laboratory SP 112870 DO 10.1101/112870 A1 Katherine M. Siewert A1 Benjamin F. Voight YR 2017 UL http://biorxiv.org/content/early/2017/03/01/112870.abstract AB Balancing selection preserves multiple alleles at a locus over long evolutionary time periods. A characteristic signature of balancing selection is an excess number of intermediate frequency polymorphisms nearby the balanced site. However, the expected distribution of allele frequencies at these loci has not been extensively detailed. We use simulations to show that new mutations that arise very close to a site targeted by long term balancing selection accumulate at frequencies nearly identical to that of the frequency of the balanced allele to which they are linked. To capture this unique signature, we propose a new summary statistic, β. Compared to existing summary statistics, simulation studies show that our statistic has improved power to detect balancing selection, and is reasonably powered in non-equilibrium demographic models or when recombination or mutation rate varies. We compute β on 1000 Genomes Project data, to identify loci potentially subjected to long-term balancing selection in humans. We report two balanced haplotypes - localized to the genes WFS1 and CADM2 - that are strongly linked to association signals for complex traits. Our approach is computationally efficient and applicable to species that lack appropriate outgroup sequences, allowing for well-powered analysis of selection in the wide variety of species for which population data is rapidly being generated.