Extended Data Fig. 6: Evidence for selection on RA-associated SNPs.
From: Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations
a) Stacked line plot of the pan-ancestry PALM analysis for RA, showing the contribution of SNPs to disease risk over time. SNPs are shown as stacked lines, the width of each line being proportional to the population frequency of the positive risk allele, weighted by its effect size. When a line widens over time the positive risk allele has increased in frequency, and vice versa. SNPs are sorted by the magnitude and direction of selection, with positively selected SNPs at the top, negatively selected SNPs at the bottom, and neutral SNPs in the middle. SNPs are coloured by their corresponding p-value in a single locus selection test. The asterisk marks the Bonferroni corrected significance threshold, and nominally significant SNPs are shown in yellow and labelled by their rsIDs. SNPs marked with the dagger symbol are located in the HLA locus. The Y-axis shows the scaled average polygenic risk score (PRS) in the population, ranging from 0 to 1, with 1 corresponding to the maximum possible average PRS (i.e. when all individuals in the population are homozygous for all positive risk alleles) and the X-axis shows time in units of thousands of years before present (kyr BP). b) Posterior likelihood trajectory for rs660895, tagging HLA-DRB1*04:01, inferred by CLUES. Statistical significance was assessed by applying a Bonferroni correction for the number of tests performed for each trait.
