Last updated: 2021-10-26

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Rmd db3c6f9 Jing Gu 2021-10-26 test enrichment for asthma risk variants

cell-type specific annotations

Caldero et al. 2019 - ATAC-Seq data for FACS-sorted cells from whole blood
I extracted ATAC-Seq peaks specific to each immune cell type from the count table that consists of a union set of peaks across cells based on the provided cutoffs.

Rheumatoid arthritis

This analysis was done to replicate the enrichment results from figure 5b in the paper. Overall, the magnitude of enrichment estimates are much smaller than that in figure 5b. I could not find their resouce of GWAS dataset, but I believe that I used a different GWAS data set for RA. They claimed 20% per-SNP heritability for RA, while the dataset in 2014 I used only found 8% genome-wide heritability. They used LDSC to estimate enrichment estimates. The stimulated immune cells tend to have slightly higher enrichment estimates, but not as significant due to overlapped CIs. However, the figure in the paper demonstrates strong enrichment of stimulated-related peaks for cells such as Bulk B, naive B, CD8+ T and Th1.

Version Author Date
5b65bd1 Jing Gu 2021-10-26

Adult-Onset Asthma

For Asthma, we did not see stronger enrichment of stimulated-related peaks compared with resting ones. But overall all immune cells whether or not stimulated (except for the stimulated mature NK) are significantly enriched for GWAS risk variants.

Version Author Date
5b65bd1 Jing Gu 2021-10-26

Allergy

Version Author Date
5b65bd1 Jing Gu 2021-10-26

Joint Enrichment of a pair of annotations

Adult-Onset Asthma

A pair of annotations - stimulated and resting for each immune cell type was jointly tested for their enrichment of GWAS risk variants. We observed many cell types share GWAS association signals. Conditional on resting cells,there are five stimulated cell types still show enrichment including Naive B, Memory B, CD8+ T , Naive CD8+ T and Naive Tregs cells.

Version Author Date
5b65bd1 Jing Gu 2021-10-26

Annotations - Differential accessible peaks

Caldero et al. 2019

  • Significant differentially accessible regions when compared to progenitor cells
  • Significant differentially accessible regions under stimulation

Version Author Date
5b65bd1 Jing Gu 2021-10-26

sessionInfo()
R version 4.0.4 (2021-02-15)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Scientific Linux 7.4 (Nitrogen)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.3.13-el7-x86_64/lib/libopenblas_haswellp-r0.3.13.so

locale:
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[11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
[1] knitr_1.31      ggplot2_3.3.3   workflowr_1.6.2

loaded via a namespace (and not attached):
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