References scRNA

The OneK1K cohort consists of single-cell RNA sequencing (scRNA-seq) data from 1.27 million peripheral blood mononuclear cells (PMBCs) collected from 982 donors. We developed a framework for the classification of individual cells, and by combining the scRNA-seq data with genotype data, we mapped the genetic effects on gene expression in each of 14 immune cell types and identified 26,597 independent cis–expression quantitative trait loci (eQTLs).

The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type-specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.