A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis - Sorbonne Université Access content directly
Journal Articles Nature Communications Year : 2019

A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

Steffan D Bos
  • Function : Author
Ashley Beecham
  • Function : Author
Jacob Mccauley
  • Function : Author
Till F M Andlauer
  • Function : Author
Lisa F Barcellos
  • Function : Author
Tone Berge
  • Function : Author
Luisa Bernardinelli
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Filippo Martinelli-Boneschi
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David R Booth
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Farren Briggs
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Elisabeth G Celius
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Manuel Comabella
  • Function : Author
Giancarlo Comi
  • Function : Author
Sandra D’alfonso
  • Function : Author
Katrina Dedham
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Pierre Duquette
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Efthimios Dardiotis
  • Function : Author
Federica Esposito
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Christiane Gasperi
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An Goris
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Bénédicte Dubois
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Georgios Hadjigeorgiou
  • Function : Author
Jonathan Haines
  • Function : Author
Clive Hawkins
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Bernhard Hemmer
  • Function : Author
Rogier Hintzen
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Dana Horakova
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Noriko Isobe
  • Function : Author
Seema Kalra
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Jun-Ichi Kira
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Michael Khalil
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Ingrid Kockum
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Christina M Lill
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Felix Luessi
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Roland Martin
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Annette Oturai
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Aarno Palotie
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Margaret A Pericak-Vance
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Janna Saarela
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Adrian Ivinson
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Tomas Olsson
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Bruce V Taylor
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Graeme J Stewart
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Hanne F Harbo
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Alastair Compston
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Frauke Zipp
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Philip de Jager
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Stephen Sawcer
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Abstract

International Multiple Sclerosis Genetics Consortium Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intraindividual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available.
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hal-04443990 , version 1 (07-02-2024)

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Lohith Madireddy, Nikolaos A Patsopoulos, Chris Cotsapas, Steffan D Bos, Ashley Beecham, et al.. A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis. Nature Communications, 2019, 10, ⟨10.1038/s41467-019-09773-y⟩. ⟨hal-04443990⟩
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