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

• DOI: 10.1126/science.1246949
• Publication Date: 2014-03-07T00:25:26Z
• Authors: Benjamin P. Fairfax; Peter Humburg; Seiko Makino; Vivek Naranbhai; Daniel Wong; Evelyn Lau; Luke Jostins; Katharine Plant; Robert Andrews; Chris McGee; Julian C. Knight
• Keywords: Adult; Male; Lipopolysaccharide Receptors; Chromosome Mapping; Genetic Variation; Immunity, Innate; 3. Good health; CARD Signaling Adaptor Proteins; Interferon-gamma; Basic-Leucine Zipper Transcription Factors; Crohn Disease; Gene Expression Regulation; Cytochrome P-450 CYP1B1; Interferon Regulatory Factors; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Female; Genetic Predisposition to Disease; Aryl Hydrocarbon Hydroxylases; Interferon Regulatory Factor-2; Genome-Wide Association Study

Immune Variation

It is difficult to determine the mechanistic consequences of context-dependent genetic variants, some of which may be related to disease (see the Perspective by

Gregersen

). Two studies now report on the effects of stimulating immunological monocytes and dendritic cells with proteins that can elicit a response to bacterial or viral infection and assess the functional links between genetic variants and profiles of gene expression.

M. N. Lee et al.

( 10.1126/science.1246980 ) analyzed the expression of more than 400 genes, in dendritic cells from 30 healthy subjects, which revealed how expression quantitative trait loci (eQTLs) affect gene expression within the interferon-β and the Toll-like receptor 3 and 4 pathways.

Fairfax et al.

( 10.1126/science.1246949 ) performed a genome-wide analysis to show that many eQTLs affected monocyte gene expression in a stimulus- or time-specific manner.