rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis

Yuki Hitomi, Yoshihiro Aiba, Yosuke Kawai, Kaname Kojima, Kazuko Ueno, Nao Nishida, Minae Kawashima, Olivier Yves Rene Michel Gervais, Seik Soon Khor, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura, Makoto Tsuiji

研究成果: Article査読

抄録

Primary biliary cholangitis (PBC) is a chronic, progressive cholestatic liver disease in which intrahepatic bile ducts are destroyed by an autoimmune reaction. Our previous genome-wide association study (GWAS) identified chromosome 11q23.1 as a susceptibility gene locus for PBC in the Japanese population. Here, high-density association mapping based on single nucleotide polymorphism (SNP) imputation and in silico/in vitro functional analyses identified rs1944919 as the primary functional variant. Expression-quantitative trait loci analyses showed that the PBC susceptibility allele of rs1944919 was significantly associated with increased COLCA1/COLCA2 expression levels. Additionally, the effects of rs1944919 on COLCA1/COLCA2 expression levels were confirmed using genotype knock-in versions of cell lines constructed using the CRISPR/Cas9 system and differed between rs1944919-G/G clones and -T/T clones. To our knowledge, this is the first study to demonstrate the contribution of COLCA1/COLCA2 to PBC susceptibility.

本文言語English
論文番号4557
ジャーナルScientific reports
11
1
DOI
出版ステータスPublished - 2021 12

ASJC Scopus subject areas

  • 一般

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