Search for: All records

The genetic variants introduced into the ancestors of modern humans from interbreeding with Neanderthals have been suggested to contribute an unexpected extent to complex human traits. However, testing this hypothesis has been challenging due to the idiosyncratic population genetic properties of introgressed variants. We developed rigorous methods to assess the contribution of introgressed Neanderthal variants to heritable trait variation and applied these methods to analyze 235,592 introgressed Neanderthal variants and 96 distinct phenotypes measured in about 300,000 unrelated white British individuals in the UK Biobank. Introgressed Neanderthal variants make a significant contribution to trait variation (explaining 0.12% of trait variation on average). However, the contribution of introgressed variants tends to be significantly depleted relative to modern human variants matched for allele frequency and linkage disequilibrium (about 59% depletion on average), consistent with purifying selection on introgressed variants. Different from previous studies (McArthur et al., 2021), we find no evidence for elevated heritability across the phenotypes examined. We identified 348 independent significant associations of introgressed Neanderthal variants with 64 phenotypes. Previous work (Skov et al., 2020) has suggested that a majority of such associations are likely driven by statistical association with nearby modern human variants that are the true causal variants. Applying a customized fine-mapping led us to identify 112 regions across 47 phenotypes containing 4303 unique genetic variants where introgressed variants are highly likely to have a phenotypic effect. Examination of these variants reveals their substantial impact on genes that are important for the immune system, development, and metabolism. 

Abstract High‐throughput sequencing has changed many aspects of population genetics, molecular ecology and related fields, affecting both experimental design and data analysis. The software packageangsdallows users to perform a number of population genetic analyses on high‐throughput sequencing data.angsduses probabilistic approaches which can directly make use of genotype likelihoods; thus,SNPcalling is not required for comparative analyses. This takes advantage of all the sequencing data and produces more accurate results for samples with low sequencing depth. Here, we presentangsd‐wrapper, a set of wrapper scripts that provides a user‐friendly interface for runningangsdand visualizing results.angsd‐wrapper supports multiple types of analyses including estimates of nucleotide sequence diversity neutrality tests, principal component analysis, estimation of admixture proportions for individual samples and calculation of statistics that quantify recent introgression.angsd‐wrapper also provides interactive graphing ofangsdresults to enhance data exploration. We demonstrate the usefulness ofangsd‐wrapper by analysing resequencing data from populations of wild and domesticatedZea.angsd‐wrapper is freely available fromhttps://github.com/mojaveazure/angsd-wrapper.