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Complex genetic signatures in immune cells underlie autoimmunity and inform therapy.

Valeria OrrùMaristella SteriCarlo SidoreMichele MarongiuValentina SerraStefania OllaGabriella SoleSandra LaiMariano DeiAntonella MulasFrancesca VirdisMaria Grazia PirasMonia LobinaMara MarongiuMaristella PitzalisFrancesca DeiddaAnnalisa LoizeddaStefano OnanoMagdalena ZoledziewskaStephen SawcerMarcella DevotoMyriam GorospeGonçalo R AbecasisMatteo FlorisMauro PalaDavid SchlessingerEdoardo FiorilloFrancesco Cucca
Published in: Nature genetics (2020)
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.
Keyphrases
  • genome wide
  • single cell
  • cell therapy
  • copy number
  • dna methylation
  • multiple sclerosis
  • gene expression
  • stem cells
  • smoking cessation
  • genome wide association study
  • electronic health record