Open AccessComplex genetic signatures in immune cells underlie autoimmunity and inform therapy
Author(s) -
Valeria Orrù,
Maristella Steri,
Carlo Sidore,
Michele Marongiu,
Valentina Serra,
Stefania Olla,
Gabriella Sole,
Sandra Lai,
Mariano Dei,
Antonella Mulas,
Francesca Virdis,
Maria Grazia Piras,
Monia Lobina,
Mara Marongiu,
Maristella Pitzalis,
Francesca Deidda,
Annalisa Loizedda,
Stefano Onano,
Magdalena Żołędziewska,
Stephen Sawcer,
Marcella Devoto,
Myriam Gorospe,
Gonçalo R. Abecasis,
Matteo Floris,
Mauro Pala,
David Schlessinger,
Edoardo Fiorillo,
Francesco Cucca
Publication year - 2020
Publication title -
nature genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 18.861
H-Index - 573
eISSN - 1546-1718
pISSN - 1061-4036
DOI - 10.1038/s41588-020-0684-4
Subject(s) - biology , autoimmunity , immune system , autoimmune disease , phenotype , disease , genome wide association study , immunology , pathogenesis , genetics , cell , genetic association , gene , genotype , single nucleotide polymorphism , medicine , antibody
We report on the influence of ~22 million variants on 731 immune cell traits in a cohort of 3,757 Sardinians. We detected 122 significant (P < 1.28 × 10 -11 ) independent association signals for 459 cell traits at 70 loci (53 of them novel) identifying several molecules and mechanisms involved in cell regulation. Furthermore, 53 signals at 36 loci overlapped with previously reported disease-associated signals, predominantly for autoimmune disorders, highlighting intermediate phenotypes in pathogenesis. Collectively, our findings illustrate complex genetic regulation of immune cells with highly selective effects on autoimmune disease risk at the cell-subtype level. These results identify drug-targetable pathways informing the design of more specific treatments for autoimmune diseases.