Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE [Database of Immune Cell Expression, Expression quantitative trait loci (eQTLs) and Epigenomics] project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis.]]>
Screening by questionnaire was used to exclude donors with known autoimmune and infectious diseases; both healthy male and female volunteers in the greater San Diego area between the ages of 18-65 were included in the study. Final blood study contains 91 donors, 15 of which donated for longitudinal samples (total n=106).]]>
Donor recruitment and collection of leukapheresis samples, including collection of longitudinal samples, were carried out between October 2014 and June 2015, followed by genotyping of donors. Subsequently, fluorescence-activated cell sorting (FACS) was carried out in multiple rounds to purify various immune cell types from frozen PBMC stocks, followed by RNA isolation and library preparations for RNA-Seq.]]>