GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
31 Jan 2024
31 Jan 2024
Historique:
received:
20
03
2023
accepted:
18
12
2023
medline:
1
2
2024
pubmed:
1
2
2024
entrez:
31
1
2024
Statut:
epublish
Résumé
Here we report the largest Asian genome-wide association study (GWAS) for systemic sclerosis performed to date, based on data from Japanese subjects and comprising of 1428 cases and 112,599 controls. The lead SNP is in the FCGR/FCRL region, which shows a penetrating association in the Asian population, while a complete linkage disequilibrium SNP, rs10917688, is found in a cis-regulatory element for IRF8. IRF8 is also a significant locus in European GWAS for systemic sclerosis, but rs10917688 only shows an association in the presence of the risk allele of IRF8 in the Japanese population. Further analysis shows that rs10917688 is marked with H3K4me1 in primary B cells. A meta-analysis with a European GWAS detects 30 additional significant loci. Polygenic risk scores constructed with the effect sizes of the meta-analysis suggest the potential portability of genetic associations beyond populations. Prioritizing the top 5% of SNPs of IRF8 binding sites in B cells improves the fitting of the polygenic risk scores, underscoring the roles of B cells and IRF8 in the development of systemic sclerosis. The results also suggest that systemic sclerosis shares a common genetic architecture across populations.
Identifiants
pubmed: 38296975
doi: 10.1038/s41467-023-44541-z
pii: 10.1038/s41467-023-44541-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
319Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP21ek0109555
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP21tm0424220
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP21ck0106642
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP23ek0410114
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP23tm0424225
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP20H00462
Informations de copyright
© 2024. The Author(s).
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