Supporting data for: Mapping genetic effects on cell type-specific chromatin accessibility and annotating complex immune trait variants using single nucleus ATAC-seq in peripheral blood

Summary

In this study we performed single nucleus ATAC-seq (snATAC-seq) and genotyping in peripheral blood mononuclear cells from 13 individuals. Clustering chromatin accessibility profiles of 96,002 total nuclei identified 17 immune cell types and sub-types. We mapped chromatin accessibility QTLs (caQTLs) in each immune cell type and sub-type using individuals of European ancestry which identified 6,901 total caQTLs at FDR <10%. For 3,941 caQTLs we further annotated putative target genes of variant activity using single cell co-accessibility. We fine-mapped loci associated with 16 complex immune traits and identified immune cell caQTLs at 622 candidate causal variants.

Raw sequence data are available in NCBI GEO accession GSE199253 and GSE163160.

Description of processed data deposited here:

0_snATAC_cluster_lables_and_qc.txt : Final list of barcodes, annotated with UMAP coordinates, sample and cell type labels and QC metrics.

1_peaks_coordinates.zip : Output of MACS2 peak calling for individual cell subtypes (NARROW.PEAKS)

act_cd4_t_peaks.narrowPeak

adaptive_NK_peaks.narrowPeak

cDC_peaks.narrowPeak

cMono_peaks.narrowPeak

cyto_cd8_t_peaks.narrowPeak

cyto_nk_peaks.narrowPeak

iMono_peaks.narrowPeak

mem_b_peaks.narrowPeak

mem_cd8_t_peaks.narrowPeak

mkc_peaks.narrowPeak

naive_b_peaks.narrowPeak

naive_cd4_t_peaks.narrowPeak

naive_cd8_t_peaks.narrowPeak

ncMono_peaks.narrowPeak

pDC_peaks.narrowPeak

plasma_peaks.narrowPeak

tReg_peaks.narrowPeak

2_co-accessibility.zip : Co-accessibility results (Cicero) of snATAC in four major blood cell types (BEDPE)

t.filtered_coaccessible_sites4s.txt

nk.filtered_coaccessible_sites4s.txt

mono.filtered_coaccessible_sites4s.txt

b.filtered_coaccessible_sites4s.txt

annotated.coaccessible.matrix4s

3_genome_browser_tracks.zip: Genome browser tracks of PBMC cell types and subtypes (BIGWIG)

pbmc1_15.tReg.scale_1e6.bw

pbmc1_15.plasma.scale_1e6.bw

pbmc1_15.naive_cd4_t.scale_1e6.bw

pbmc1_15.naive_cd8_t.scale_1e6.bw

pbmc1_15.ncMono.scale_1e6.bw

pbmc1_15.mem_cd8_t.scale_1e6.bw

pbmc1_15.naive_b.scale_1e6.bw

pbmc1_15.mem_b.scale_1e6.bw

pbmc1_15.cyto_nk.scale_1e6.bw

pbmc1_15.iMono.scale_1e6.bw

pbmc1_15.cyto_cd8_t.scale_1e6.bw

pbmc1_15.cMono.scale_1e6.bw

pbmc1_15.cDC.scale_1e6.bw

pbmc1_15.adaptive_NK.scale_1e6.bw

pbmc1_15.act_cd4_t.scale_1e6.bw

4_summary_stats.zip: Summary statistics of caQTLs in PBMC cell types, subtypes, and “bulk” like data (TSV)

## Lead only combined

EUR_caqtl_leads_run3.tsv

## Bulk-like

bulk_caqtl_sumstats_run3.tsv

## Cell types

b_caqtl_sumstats_run3.tsv   

t_caqtl_sumstats_run3.tsv

nk_caqtl_sumstats_run3.tsv

mono_caqtl_sumstats_run3.tsv

## Cell subtypes

tReg_caqtl_sumstats_run3.tsv

naive_cd4_t_caqtl_sumstats_run3.tsv

naive_cd8_t_caqtl_sumstats_run3.tsv

ncMono_caqtl_sumstats_run3.tsv

naive_b_caqtl_sumstats_run3.tsv

mem_cd8_t_caqtl_sumstats_run3.tsv

mkc_caqtl_sumstats_run3.tsv

mem_b_caqtl_sumstats_run3.tsv

iMono_caqtl_sumstats_run3.tsv

cyto_nk_caqtl_sumstats_run3.tsv

cyto_cd8_t_caqtl_sumstats_run3.tsv

cMono_caqtl_sumstats_run3.tsv

cDC_caqtl_sumstats_run3.tsv

cd8_t_caqtl_sumstats_run3.tsv

cd4_t_caqtl_sumstats_run3.tsv

adaptive_NK_caqtl_sumstats_run3.tsv

act_cd4_t_caqtl_sumstats_run3.tsv

5_credible_sets.zip: Fine-mapping credible sets for loci associated with 16 complex immune traits (BED)

Ulcerative_colitis.99credset.PPA.bed

Type_1_diabetes.99credset.PPA.bed

Systemic_lupus_erythematosus.99credset.PPA.bed

Rheumatoid_arthritis.99credset.PPA.bed

Selective_IgA_deficiency.99credset.PPA.bed

Primary_sclerosing_cholangitis.99credset.PPA.bed

Monocyte_count.99credset.PPA.bed

Neutrophil_count.99credset.PPA.bed

Lymphocyte_count.99credset.PPA.bed

Gout.99credset.PPA.bed

Eosinophil_count.99credset.PPA.bed

Crohns_disease.99credset.PPA.bed

Basophil_count.99credset.PPA.bed

Autoimmune_vitiligo.99credset.PPA.bed

Atopic_dermatitis.99credset.PPA.bed

Asthma_child_onset.99credset.PPA.bed