Mosaic loss of chromosome Y characterises late-onset rheumatoid arthritis and contrasting associations of polygenic risk score based on age at onset.

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Tác giả: Giulio Genovese, Takahisa Gono, Keiko Hikino, Suguru Honda, Katsunori Ikari, Yuki Ishikawa, Yoichiro Kamatani, Masataka Kuwana, Eiichi Tanaka, Chikashi Terao, Shunsuke Uchiyama

Ngôn ngữ: eng

Ký hiệu phân loại: 809.008 History and description with respect to kinds of persons

Thông tin xuất bản: England : Annals of the rheumatic diseases , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 577009

 OBJECTIVES: Mosaic chromosomal alterations (mCAs) increase with age and are associated with age-related diseases. The association between mCAs and rheumatoid arthritis (RA), particularly late-onset RA (LORA), has not been explored. METHODS: mCAs were detected in peripheral blood samples from 2 independent Japanese datasets (Set 1: 2107 RA cases and 86,998 controls
  Set 2: 2359 RA cases and 86,998 controls). The associations between mCAs and RA were evaluated in each dataset using logistic regression models and meta-analysis. In each dataset, the effect sizes of mosaic loss of Y (mLOY) and polygenic risk score (PRS) of RA in males was evaluated, and a meta-analysis was subsequently performed. The interaction between mLOY and PRS was assessed. These models were applied separately to RA, LORA, and young-onset RA (YORA). RESULTS: mLOY increased significantly in LORA (odds ratio [OR] = 1.43, P = .0070). We observed a negative association between mLOY and YORA (OR = 0.66, P = .0034). On the other hand, we found consistently negative associations of autosomal mCAs or mosaic loss of X with RA, LORA, and YORA. The PRS effect sizes were lower for LORA than for YORA. mLOY with a high cell fraction strengthened the association between PRS and LORA (P = .0036), whereas the association with YORA was independent of mLOY. CONCLUSIONS: LORA was characterised by the presence of a high burden of mLOY. The observed interaction between mLOY and PRS in LORA, but not in YORA, supports different gene-environment interactions between the subsets. These data suggest that distinct pathophysiological mechanisms underlie the development of LORA and YORA.
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