title: Genome-wide analysis of the genetic regulation of gene expression in human neutrophils.
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 β-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.
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Anand Kumar
authors.initials: AK
authors.lastname: Andiappan
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Rossella
authors.initials: R
authors.lastname: Melchiotti
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Tuang Yeow
authors.initials: TY
authors.lastname: Poh
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Michelle
authors.initials: M
authors.lastname: Nah
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Kia Joo
authors.initials: KJ
authors.lastname: Puan
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Elena
authors.initials: E
authors.lastname: Vigano
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Doreen
authors.initials: D
authors.lastname: Haase
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Nurhashikin
authors.initials: N
authors.lastname: Yusof
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Boris
authors.initials: B
authors.lastname: San Luis
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Josephine
authors.initials: J
authors.lastname: Lum
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Dilip
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Shihui
authors.initials: S
authors.lastname: Foo
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Li
authors.initials: L
authors.lastname: Zhuang
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Anusha
authors.initials: A
authors.lastname: Vasudev
authors.affiliation: Department of Human Genetics, Genome institute of Singapore (GIS), Singapore, Singapore.
authors.forename: Astrid
authors.initials: A
authors.lastname: Irwanto
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Bernett
authors.initials: B
authors.lastname: Lee
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nardin
authors.affiliation: Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, Shandong, China.|Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China.|School of Medicine, Shandong University, Shandong Provincial Medical Center for Dermatovenereology, Jinan, Shandong, China.|Shandong Provincial Institute of Dermatology and Venereology, Provincial Academy of Medical Science, Jinan, Shandong, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Shandong Provincial Hospital for Skin Diseases, Shandong University, Jinan, Shandong, China.|Shandong Provincial Institute of Dermatology and Venereology, Shandong Academy of Medical Sciences, Jinan, Shandong, China.|School of Medicine, Shandong University, Shandong Provincial Medical Center for Dermatovenereology, Jinan, Shandong, China.|Shandong Provincial Institute of Dermatology and Venereology, Provincial Academy of Medical Science, Jinan, Shandong, China.
authors.forename: Furen
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: John
authors.initials: J
authors.lastname: Connolly
authors.affiliation: Department of Human Genetics, Genome institute of Singapore (GIS), Singapore, Singapore.|School of Life Sciences, Anhui Medical University, Hefei, Anhui, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Alessandra
authors.identifier: http://orcid.org/0000-0003-1744-2430
authors.initials: A
authors.lastname: Mortellaro
authors.affiliation: Department of Otolaryngology, National University of Singapore, Singapore.
authors.forename: De Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Michael
authors.identifier: http://orcid.org/0000-0002-1047-2277
authors.initials: M
authors.lastname: Poidinger
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Anis
authors.initials: A
authors.lastname: Larbi
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zolezzi
authors.affiliation: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), #04-06, 8A Biomedical Grove, Singapore, Singapore.
authors.forename: Olaf
authors.initials: O
authors.lastname: Rotzschke
mesh_terms: D000293:Adolescent; D000328:Adult; D016000:Cluster Analysis; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D055815:Young Adult