Gene | Condition | Pvalue | FDR | PST | ΔPST cis |
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Gene | Condition | Pvalue | FDR |
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Genetic Ancestry and Natural Selection Drive Population Differences in Immune Responses to Pathogens
Yohann Nédélec, Joaquín Sanz, Golshid Baharian, Zachary A. Szpiech, Alain Pacis, Anne Dumaine, Jean-Christophe Grenier, Andrew Freiman, Aaron J. Sams, Steven Hebert, Ariane Pagé Sabourin, Francesca Luca, Ran Blekhman, Ryan D. Hernandez, Roger Pique-Regi, Jenny Tung, Vania Yotova, Luis B. Barreiro
Cell, october 2016
We studied the impact of a genetic variant (SNP in our case) on different gene regulatory traits:
All linear regressions were performed using the R package Matrix eQTL.
We tested SNPs with a minor allele frequency above 5% and falling in a +/- 100 Kb region around each gene (in our data, it represents ~ 3M SNPs).
A SNP can be missing because:
A gene can be missing because :
To detect differences in isoform usage between African-Americans and European-Americans, we applied a multivariate generalization of the Welch’s t-test, which allowed us to test for differences in the distribution of gene isoform usage for all isoforms at once.
To investigate the regulatory mechanisms that account for immune QTL, we next profiled the genome-wide chromatin accessibility landscape of non-infected, Listeria and Salmonella-infected cells using ATAC-seq. Using ATAC-seq footprinting we identified transcription factor (TF) binding motifs likely to be occupied by their respective TFs in each of the experimental conditions studied. For each SNP we report the list of TF binding sites it overlaps (if any).
PST is the phenotypic analog of the population genetic parameter FST, providing a measure of the proportion of overall gene expression variance explained by between-population phenotypic divergence. PST values range from 0 to 1, with values close to 1 implying that the majority of a gene’s expression variance is due to differences between populations. ΔPST quantifies the proportion of ancestry-associated expression level differences that stem from the strongest cis-associated variant.