論文

2023年3月6日

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

International Journal of Molecular Sciences
  • 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
  • 全て表示

24
5
開始ページ
5019
終了ページ
5019
記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/ijms24055019
出版者・発行元
MDPI AG

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.

リンク情報
DOI
https://doi.org/10.3390/ijms24055019
URL
https://www.mdpi.com/1422-0067/24/5/5019/pdf
ID情報
  • DOI : 10.3390/ijms24055019
  • eISSN : 1422-0067

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