Genetic Architecture of Adaptive Immune System Identifies Key Immune Regulators | Zendy

Vasiliki Lagou | Zendy; Josselyn E. GarciaPerez | Zendy; Ide Smets | Zendy; Lies Van Horebeek | Zendy; Marijne Vandebergh | Zendy; Liye Chen | Zendy; Klara Mallants | Zendy; Teresa Prezzemolo | Zendy; Kelly Hilven | Zendy; Stéphanie HumbletBaron | Zendy; Matthieu Moisse | Zendy; Philip Van Damme | Zendy; Guy E. Boeckxstaens | Zendy; Paul Bowness | Zendy; Bénédicte Dubois | Zendy; James Dooley | Zendy; Adrian Liston | Zendy; An Goris | Zendy

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Genetic Architecture of Adaptive Immune System Identifies Key Immune Regulators

Author(s) -

Vasiliki Lagou,

Josselyn E. GarciaPerez,

Ide Smets,

Lies Van Horebeek,

Marijne Vandebergh,

Liye Chen,

Klara Mallants,

Teresa Prezzemolo,

Kelly Hilven,

Stéphanie HumbletBaron,

Matthieu Moisse,

Philip Van Damme,

Guy E. Boeckxstaens,

Paul Bowness,

Bénédicte Dubois,

James Dooley,

Adrian Liston,

An Goris

Publication year - 2018

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2018.09.048

Subject(s) - biology , genome wide association study , immune system , genetic architecture , genetic association , phenotype , acquired immune system , genetics , immunology , gene , genotype , single nucleotide polymorphism

The immune system is highly diverse, but characterization of its genetic architecture has lagged behind the vast progress made by genome-wide association studies (GWASs) of emergent diseases. Our GWAS for 54 functionally relevant phenotypes of the adaptive immune system in 489 healthy individuals identifies eight genome-wide significant associations explaining 6%-20% of variance. Coding and splicing variants in PTPRC and COMMD10 are involved in memory T cell differentiation. Genetic variation controlling disease-relevant T helper cell subsets includes RICTOR and STON2 associated with Th2 and Th17, respectively, and the interferon-lambda locus controlling regulatory T cell proliferation. Early and memory B cell differentiation stages are associated with variation in LARP1B and SP4. Finally, the latrophilin family member ADGRL2 correlates with baseline pro-inflammatory interleukin-6 levels. Suggestive associations reveal mechanisms of autoimmune disease associations, in particular related to pro-inflammatory cytokine production. Pinpointing these key human immune regulators offers attractive therapeutic perspectives.

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