Genome-wide analysis of the genetic regulation of gene expression in human neutrophils

Anand Kumar Andiappan, Rossella Melchiotti, Tuang Yeow Poh, Michelle Nah, Kia Joo Puan, Elena Vigano, Doreen Haase, Nurhashikin Yusof, Boris San Luis, Josephine Lum, Dilip Kumar, Shihui Foo, Li Zhuang, Anusha Vasudev, Astrid Irwanto, Bernett Lee, Alessandra Nardin, Hong Liu, Furen Zhang, John Connolly, Jianjun Liu, Alessandra Mortellaro, Wang De Yun, Michael Poidinger, Anis Larbi, Francesca Zolezzi and Olaf Rotzschke ()
Additional contact information
Anand Kumar Andiappan: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Rossella Melchiotti: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Tuang Yeow Poh: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Michelle Nah: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Kia Joo Puan: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Elena Vigano: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Doreen Haase: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Nurhashikin Yusof: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Boris San Luis: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Josephine Lum: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Dilip Kumar: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Shihui Foo: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Li Zhuang: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Anusha Vasudev: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Astrid Irwanto: Genome institute of Singapore (GIS)
Bernett Lee: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Alessandra Nardin: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Hong Liu: Shandong Provincial Hospital for Skin Diseases, Shandong University
Furen Zhang: Shandong Provincial Hospital for Skin Diseases, Shandong University
John Connolly: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Jianjun Liu: Genome institute of Singapore (GIS)
Alessandra Mortellaro: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Wang De Yun: National University of Singapore
Michael Poidinger: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Anis Larbi: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Francesca Zolezzi: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)
Olaf Rotzschke: Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR)

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms8971

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