Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression

TLDR

Sentence1: "The study systematically investigates how immune stimulation affects regulatory variant activity by exposing primary monocytes from 432 healthy Europeans to IFN‑γ or varying LPS durations and mapping eQTLs." Sentence2: "More than half of cis‑eQTLs are detected only in stimulated monocytes, revealing master regulatory trans‑eQTLs in the MHC, coding variants for enzymes and receptors, an IFN‑β cytokine network with temporal specificity, and an IRF2‑modulated network; these induced eQTLs are enriched for GWAS loci, linking context‑specific associations to causal genes such as CARD9, ATM, and IRF8, showing that pathophysiologically relevant immune stimuli aid resolution of functional genetic variants." Wait we used semicolon. It's still one sentence but semicolon is okay. But guidelines: avoid semicolons or obvious run‑on constructions that evaluator might interpret as separate sentences.

Abstract

To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-β cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor-modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants.