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Genome-Wide Association Study and Transcriptome of Japanese Patients with Developmental Dysplasia of the Hip Demonstrates an Association with the Ferroptosis Signaling Pathway

Authors :
Yu Mori
Kazuko Ueno
Daisuke Chiba
Ko Hashimoto
Yosuke Kawai
Kazuyoshi Baba
Hidetatsu Tanaka
Takashi Aki
Masanori Ogasawara
Naoto Shibasaki
Katsushi Tokunaga
Toshimi Aizawa
Masao Nagasaki
Source :
International Journal of Molecular Sciences, Vol 24, Iss 5, p 5019 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

This study examined the association between developmental dysplasia of the hip (DDH) and disease-associated loci in a Japanese cohort. A genome-wide association study (GWAS) of 238 Japanese patients with DDH and 2044 healthy individuals was performed. As a replicate, GWAS was also conducted on the UK Biobank data with 3315 cases and matched 74,038 controls. Gene set enrichment analyses (GSEAs) of both the genetics and transcriptome of DDH were performed. Transcriptome analysis of cartilage specimens from DDH-associated osteoarthritis and femoral neck fractures was performed as a control. Most of the lead variants were very low-frequency ones in the UK, and variants in the Japanese GWAS could not be replicated with the UK GWAS. We assigned DDH-related candidate variants to 42 and 81 genes from the Japanese and UK GWASs, respectively, using functional mapping and annotation. GSEA of gene ontology, disease ontology, and canonical pathways identified the most enriched pathway to be the ferroptosis signaling pathway, both in the Japanese gene set as well as the Japanese and UK merged set. Transcriptome GSEA also identified significant downregulation of genes in the ferroptosis signaling pathway. Thus, the ferroptosis signaling pathway may be associated with the pathogenic mechanism of DDH.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
24
Issue :
5
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.1fff1e5cfcab46ec835bf833f9ccae74
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms24055019