Please use this identifier to cite or link to this item: https://doi.org/10.1038/ncomms8971
Title: Genome-wide analysis of the genetic regulation of gene expression in human neutrophils
Authors: Andiappan, A.K
Melchiotti, R
Poh, T.Y
Nah, M
Puan, K.J
Vigano, E
Haase, D
Yusof, N
San Luis, B
Lum, J
Kumar, D
Foo, S
Zhuang, L
Vasudev, A
Irwanto, A
Lee, B
Nardin, A
Liu, H
Zhang, F
Connolly, J 
Liu, J
Mortellaro, A
Wang, D.Y 
Poidinger, M 
Larbi, A
Zolezzi, F
Rotzschke, O
Keywords: interleukin 18
interleukin 18 receptor
allele
antimicrobial activity
cells and cell components
ethnicity
gene expression
genetic analysis
genome
hominid
immune system
immunity
leprosy
polymorphism
protein
RNA
skin disorder
adult
allele
Article
blood sampling
cell isolation
Chinese
cluster analysis
Crohn disease
disease marker
female
gene expression
genetic association
genetic regulation
human
human cell
immunopathology
inflammation
leprosy
male
neutrophil
normal human
quantitative trait locus
single nucleotide polymorphism
skin disease
adolescent
gene expression regulation
genetic linkage
genetics
genome-wide association study
genotype
metabolism
neutrophil
physiology
quantitative trait locus
young adult
China
Adolescent
Adult
Cluster Analysis
Female
Gene Expression Regulation
Genetic Linkage
Genome-Wide Association Study
Genotype
Humans
Inflammation
Male
Neutrophils
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Young Adult
Issue Date: 2015
Publisher: Nature Publishing Group
Citation: Andiappan, A.K, Melchiotti, R, Poh, T.Y, Nah, M, Puan, K.J, Vigano, E, Haase, D, Yusof, N, San Luis, B, Lum, J, Kumar, D, Foo, S, Zhuang, L, Vasudev, A, Irwanto, A, Lee, B, Nardin, A, Liu, H, Zhang, F, Connolly, J, Liu, J, Mortellaro, A, Wang, D.Y, Poidinger, M, Larbi, A, Zolezzi, F, Rotzschke, O (2015). Genome-wide analysis of the genetic regulation of gene expression in human neutrophils. Nature Communications 6 : 8971. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms8971
Rights: Attribution 4.0 International
Abstract: Neutrophils are an abundant immune cell type involved in both antimicrobial defence and autoimmunity. The regulation of their gene expression, however, is still largely unknown. Here we report an eQTL study on isolated neutrophils from 114 healthy individuals of Chinese ethnicity, identifying 21,210 eQTLs on 832 unique genes. Unsupervised clustering analysis of these eQTLs confirms their role in inflammatory responses and immunological diseases but also indicates strong involvement in dermatological pathologies. One of the strongest eQTL identified (rs2058660) is also the tagSNP of a linkage block reported to affect leprosy and Crohn's disease in opposite directions. In a functional study, we can link the C allele with low expression of the ?-chain of IL18-receptor (IL18RAP). In neutrophils, this results in a reduced responsiveness to IL-18, detected both on the RNA and protein level. Thus, the polymorphic regulation of human neutrophils can impact beneficial as well as pathological inflammatory responses.
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/180447
ISSN: 2041-1723
DOI: 10.1038/ncomms8971
Rights: Attribution 4.0 International
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