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

Abstract 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 Japan...

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Autores principales:	Yuki Hitomi, Yoshihiro Aiba, Yosuke Kawai, Kaname Kojima, Kazuko Ueno, Nao Nishida, Minae Kawashima, Olivier Gervais, Seik-Soon Khor, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura, Makoto Tsuiji
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cb5d749009044cbb96285ad674364512
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spelling	oai:doaj.org-article:cb5d749009044cbb96285ad6743645122021-12-02T15:54:01Zrs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis10.1038/s41598-021-84042-x2045-2322https://doaj.org/article/cb5d749009044cbb96285ad6743645122021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84042-xhttps://doaj.org/toc/2045-2322Abstract 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.Yuki HitomiYoshihiro AibaYosuke KawaiKaname KojimaKazuko UenoNao NishidaMinae KawashimaOlivier GervaisSeik-Soon KhorMasao NagasakiKatsushi TokunagaMinoru NakamuraMakoto TsuijiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuki Hitomi Yoshihiro Aiba Yosuke Kawai Kaname Kojima Kazuko Ueno Nao Nishida Minae Kawashima Olivier Gervais Seik-Soon Khor Masao Nagasaki Katsushi Tokunaga Minoru Nakamura Makoto Tsuiji rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis
description	Abstract 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.
format	article
author	Yuki Hitomi Yoshihiro Aiba Yosuke Kawai Kaname Kojima Kazuko Ueno Nao Nishida Minae Kawashima Olivier Gervais Seik-Soon Khor Masao Nagasaki Katsushi Tokunaga Minoru Nakamura Makoto Tsuiji
author_facet	Yuki Hitomi Yoshihiro Aiba Yosuke Kawai Kaname Kojima Kazuko Ueno Nao Nishida Minae Kawashima Olivier Gervais Seik-Soon Khor Masao Nagasaki Katsushi Tokunaga Minoru Nakamura Makoto Tsuiji
author_sort	Yuki Hitomi
title	rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis
title_short	rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis
title_full	rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis
title_fullStr	rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis
title_full_unstemmed	rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis
title_sort	rs1944919 on chromosome 11q23.1 and its effector genes colca1/colca2 confer susceptibility to primary biliary cholangitis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cb5d749009044cbb96285ad674364512
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rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis

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