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Title: Regional heritability mapping identifies several novel loci (STAT4, ULK4, and KCNH5) for primary biliary cholangitis in the Japanese population
Authors: Gervais, Olivier
Ueno, Kazuko
Kawai, Yosuke
Hitomi, Yuki
Aiba, Yoshihiro
Ueta, Mayumi
Nakamura, Minoru
Tokunaga, Katsushi
Nagasaki, Masao  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: ジェルベ, オリビエ
植野, 和子
河合, 洋介
人見, 祐基
相葉, 佳洋
上田, 真由美
中村, 稔
徳永, 勝士
長﨑, 正朗
Keywords: Genome informatics
Quantitative trait
Issue Date: 9-Apr-2021
Publisher: Springer Nature
Journal title: European Journal of Human Genetics
Abstract: While the advent of GWAS more than a decade ago has ushered in remarkable advances in our understanding of complex traits, the limitations of single-SNP analysis have also led to the development of several other approaches. Simulation studies have shown that the regional heritability mapping (RHM) method, which makes use of multiple adjacent SNPs jointly to estimate the genetic effect of a given region of the genome, generally has higher detection power than single-SNP GWAS. However, thus far its use has been mostly limited to agricultural settings, and its potential for the discovery of new genes in human diseases is yet to be fully exploited. In this study, by applying the RHM method to primary biliary cholangitis (PBC) in the Japanese population, we identified three novel loci (STAT4, ULK4, and KCNH5) at the genome-wide significance level, two of which (ULK4 and KCNH5) have not been found associated with PBC in any population previously. Notably, these genes could not be detected by using conventional single-SNP GWAS, highlighting the potential of the RHM method for the detection of new susceptibility loci in human diseases. These findings thereby provide strong empirical evidence that RHM is an effective and practical complementary approach to GWAS in this context. Also, liver tissue mRNA microarray analysis revealed higher gene expression levels in ULK4 in PBC patients (P < 0.01). Lastly, we estimated the common SNP heritability of PBC in the Japanese population (0.210 ± 0.026).
Description: 原発性胆汁性胆管炎の新たな遺伝要因を同定 --ヒト全ゲノム領域へのRHM法による世界初の成果--. 京都大学プレスリリース. 2021-04-09.
Rights: © The Author(s) 2021
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.
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DOI(Published Version): 10.1038/s41431-021-00854-5
PubMed ID: 33833419
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