상세 보기
- Tian, Chi;
- Zhang, Yuntian;
- Tong, Yihan;
- Kock, Kian Hong;
- Sim, Donald Yuhui;
- ... Park, Woong-Yang;
- 외 28명
WEB OF SCIENCE
17SCOPUS
17초록
Alternative splicing contributes to complex traits, but whether this differs in trait-relevant cell types across diverse genetic ancestries is unclear. Here we describe cell-type-specific, sex-biased and ancestry-biased alternative splicing in similar to 1 M peripheral blood mononuclear cells from 474 healthy donors from the Asian Immune Diversity Atlas. We identify widespread sex-biased and ancestry-biased differential splicing, most of which is cell-type-specific. We identify 11,577 independent cis-splicing quantitative trait loci (sQTLs), 607 trans-sGenes and 107 dynamic sQTLs. Colocalization between cis-eQTLs and trans-sQTLs revealed a cell-type-specific regulatory relationship between HNRNPLL and PTPRC. We observed an enrichment of cis-sQTL effects in autoimmune and inflammatory disease heritability. Specifically, we functionally validated an Asian-specific sQTL disrupting the 5 ' splice site of TCHP exon 4 that putatively modulates the risk of Graves' disease in East Asian populations. Our work highlights the impact of ancestral diversity on splicing and provides a roadmap to dissect its role in complex diseases at single-cell resolution.
키워드
- 제목
- Single-cell RNA sequencing of peripheral blood links cell-type-specific regulation of splicing to autoimmune and inflammatory diseases
- 저자
- Tian, Chi; Zhang, Yuntian; Tong, Yihan; Kock, Kian Hong; Sim, Donald Yuhui; Liu, Fei; Dong, Jiaqi; Jing, Zhixuan; Wang, Wenjing; Gao, Junbin; Tan, Le Min; Han, Kyung Yeon; Tomofuji, Yoshihiko; Nakano, Masahiro; Buyamin, Eliora Violain; Sonthalia, Radhika; Ando, Yoshinari; Hatano, Hiroaki; Sonehara, Kyuto; Jin, Xin; Loh, Marie; Chambers, John; Hon, Chung-Chau; Choi, Murim; Park, Jong-Eun; Ishigaki, Kazuyoshi; Okamura, Tomohisa; Fujio, Keishi; Okada, Yukinori; Park, Woong-Yang; Shin, Jay W.; Roca, Xavier; Prabhakar, Shyam; Liu, Boxiang
- 발행일
- 2024-12
- 유형
- Article
- 저널명
- Nature Genetics
- 권
- 56
- 호
- 12
- 페이지
- 2739 ~ 2752