Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 05 2023
15 05 2023
Historique:
received:
06
07
2021
accepted:
17
01
2023
medline:
17
5
2023
pubmed:
16
5
2023
entrez:
15
5
2023
Statut:
epublish
Résumé
Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.
Identifiants
pubmed: 37188663
doi: 10.1038/s41467-023-36120-z
pii: 10.1038/s41467-023-36120-z
pmc: PMC10185546
doi:
Substances chimiques
Influenza Vaccines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2709Investigateurs
Thomas Damm Als
(TD)
Adam Ziemann
(A)
Ali Abbasi
(A)
Anne Lehtonen
(A)
Apinya Lertratanakul
(A)
Bridget Riley-Gillis
(B)
Fedik Rahimov
(F)
Howard Jacob
(H)
Jeffrey Waring
(J)
Mengzhen Liu
(M)
Nizar Smaoui
(N)
Relja Popovic
(R)
Adam Platt
(A)
Athena Matakidou
(A)
Benjamin Challis
(B)
Dirk Paul
(D)
Glenda Lassi
(G)
Ioanna Tachmazidou
(I)
Antti Hakanen
(A)
Johanna Schleutker
(J)
Nina Pitkänen
(N)
Perttu Terho
(P)
Petri Virolainen
(P)
Arto Mannermaa
(A)
Veli-Matti Kosma
(VM)
Chia-Yen Chen
(CY)
Heiko Runz
(H)
Sally John
(S)
Sanni Lahdenperä
(S)
Stephanie Loomis
(S)
Susan Eaton
(S)
George Okafo
(G)
Heli Salminen-Mankonen
(H)
Marc Jung
(M)
Nathan Lawless
(N)
Zhihao Ding
(Z)
Joseph Maranville
(J)
Marla Hochfeld
(M)
Robert Plenge
(R)
Shameek Biswas
(S)
Masahiro Kanai
(M)
Mutaamba Maasha
(M)
Wei Zhou
(W)
Outi Tuovila
(O)
Raimo Pakkanen
(R)
Jari Laukkanen
(J)
Teijo Kuopio
(T)
Kristiina Aittomäki
(K)
Antti Mäkitie
(A)
Natalia Pujol
(N)
Triin Laisk
(T)
Katriina Aalto-Setälä
(K)
Johanna Mäkelä
(J)
Marco Hautalahti
(M)
Sarah Smith
(S)
Tom Southerington
(T)
Eeva Kangasniemi
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Minna Raivio
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Pentti Tienari
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Kaj Metsärinne
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Klaus Elenius
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Leena Koulu
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Markku Voutilainen
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Riitta Lahesmaa
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Roosa Kallionpää
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Sirkku Peltonen
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Tytti Willberg
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Ulvi Gursoy
(U)
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(V)
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Joel Rämö
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(R)
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Informations de copyright
© 2023. The Author(s).
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