Genomic modulators of gene expression in human neutrophils.
Vivek NaranbhaiBenjamin P FairfaxSeiko MakinoPeter HumburgDaniel WongEsther NgAdrian V S HillJulian C KnightPublished in: Nature communications (2015)
Neutrophils form the most abundant leukocyte subset and are central to many disease processes. Technical challenges in transcriptomic profiling have prohibited genomic approaches to date. Here we map expression quantitative trait loci (eQTL) in peripheral blood CD16+ neutrophils from 101 healthy European adults. We identify cis-eQTL for 3281 neutrophil-expressed genes including many implicated in neutrophil function, with 450 of these not previously observed in myeloid or lymphoid cells. Paired comparison with monocyte eQTL demonstrates nuanced conditioning of genetic regulation of gene expression by cellular context, which relates to cell-type-specific DNA methylation and histone modifications. Neutrophil eQTL are markedly enriched for trait-associated variants particularly autoimmune, allergy and infectious disease. We further demonstrate how eQTL in PADI4 and NOD2 delineate risk variant function in rheumatoid arthritis, leprosy and Crohn's disease. Taken together, these data help advance understanding of the genetics of gene expression, neutrophil biology and immune-related diseases.
Keyphrases
- dna methylation
- genome wide
- gene expression
- copy number
- peripheral blood
- infectious diseases
- rheumatoid arthritis
- endothelial cells
- induced apoptosis
- single cell
- poor prognosis
- electronic health record
- multiple sclerosis
- bone marrow
- cell cycle arrest
- rna seq
- endoplasmic reticulum stress
- systemic lupus erythematosus
- big data
- high resolution
- deep learning
- mass spectrometry
- signaling pathway
- nk cells