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Blood Proteins/*genetics
Cell Lineage/*genetics
Cohort Studies
Female
Gene Expression Profiling
*Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Male
Middle Aged
Polymorphism, Single Nucleotide/*genetics
Quantitative Trait Loci/*genetics
RNA, Messenger/*blood/genetics
Regulatory Sequences, Nucleic Acid/*genetics
Abstract:
Genetic risk factors often localize to noncoding regions of the genome with unknown effects on disease etiology. Expression quantitative trait loci (eQTLs) help to explain the regulatory mechanisms underlying these genetic associations. Knowledge of the context that determines the nature and strength of eQTLs may help identify cell types relevant to pathophysiology and the regulatory networks underlying disease. Here we generated peripheral blood RNA-seq data from 2,116 unrelated individuals and systematically identified context-dependent eQTLs using a hypothesis-free strategy that does not require previous knowledge of the identity of the modifiers. Of the 23,060 significant cis-regulated genes (false discovery rate (FDR) </= 0.05), 2,743 (12%) showed context-dependent eQTL effects. The majority of these effects were influenced by cell type composition. A set of 145 cis-eQTLs depended on type I interferon signaling. Others were modulated by specific transcription factors binding to the eQTL SNPs.
