Genetic mapping across autoimmune diseases reveals shared associations and mechanisms.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
13 May 2024
13 May 2024
Historique:
received:
29
09
2021
accepted:
21
03
2024
medline:
14
5
2024
pubmed:
14
5
2024
entrez:
13
5
2024
Statut:
aheadofprint
Résumé
Autoimmune and inflammatory diseases are polygenic disorders of the immune system. Many genomic loci harbor risk alleles for several diseases, but the limited resolution of genetic mapping prevents determining whether the same allele is responsible, indicating a shared underlying mechanism. Here, using a collection of 129,058 cases and controls across 6 diseases, we show that ~40% of overlapping associations are due to the same allele. We improve fine-mapping resolution for shared alleles twofold by combining cases and controls across diseases, allowing us to identify more expression quantitative trait loci driven by the shared alleles. The patterns indicate widespread sharing of pathogenic mechanisms but not a single global autoimmune mechanism. Our approach can be applied to any set of traits and is particularly valuable as sample collections become depleted.
Identifiants
pubmed: 38741015
doi: 10.1038/s41588-024-01732-8
pii: 10.1038/s41588-024-01732-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI122220
Pays : United States
Investigateurs
Ashley H Beecham
(AH)
Nikolaos A Patsopoulos
(NA)
Chris Cotsapas
(C)
David Booth
(D)
An Goris
(A)
Annette Oturai
(A)
Janna Saarela
(J)
Betrand Fontaine
(B)
Bertrand Hemmer
(B)
Martin Claes
(M)
Frauke Zipp
(F)
Sandra D'Alfonso
(S)
Filippo Martinelli-Boneschi
(F)
Bruce Taylor
(B)
Hanne F Harbo
(HF)
Ingrid Kockum
(I)
Jan Hillert
(J)
Tomas Olsson
(T)
Jorge R Oksenberg
(JR)
Rogier Hintzen
(R)
Lisa F Barcellos
(LF)
Lars Alfredsson
(L)
Federica Esposito
(F)
Roland Martin
(R)
Jonathan L Haines
(JL)
Margaret A Pericak-Vance
(MA)
Adrian J Ivinson
(AJ)
Graeme Stewart
(G)
David Hafler
(D)
Stephen L Hauser
(SL)
Alastair Compston
(A)
Gil McVean
(G)
Philip De Jager
(P)
Stephen J Sawcer
(SJ)
Jakob L McCauley
(JL)
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
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