Original Code for main analyses of Kerner et al., 'Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe', 2022
Description
Code for reproducing main analyses of Kerner et al., Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe (2022). In this work, we use simulations and an approximate Bayesian computation (ABC) approach based on time-series of allele frequency trajectories computed from publicly available ancient DNA (1240k capture array) to unravel candidate variants and loci under natural selection over the last 10,000 years in Europe. For candidate regions, we estimate, at the variant level, selection intensity (s) assuming an additive model with a dominance coefficient of 0.5, and onset of selection (T), i.e., the age at which selection started. We discover 89 loci, defined on the basis of LD, that are candidates for positive selection and 50 missense variants at conserved positions of the genome that are candidates (p <0.01) for negative selection. We perform enrichment analyses to assess the impact of the positively-selected loci (see scripts) and functional analyses to assess the pathogenic role of the candidate negatively-selected variants (see paper). We describe also a polygenic risk score-based approach to study the evolution of variants associated in present-day Europeans by GWAS to infectious and autoimmune traits. Code is meant to comprehend analyses relating to the main findings of this work. Folders contain code relating to 1) Scans of Selection, 2) Onset of selection analyses, 3) Enrichment analyses and 4) Polygenic risk score analyses.