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How genetic risk contributes to autoimmune liver disease
Genome-wide association studies (GWAS) for autoimmune hepatitis (AIH) and GWAS/genome-wide meta-analyses (GWMA) for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) have been successful over the past decade, identifying about 100 susceptibility loci in the human genome, wit...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256578/ https://www.ncbi.nlm.nih.gov/pubmed/35650446 http://dx.doi.org/10.1007/s00281-022-00950-8 |
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author | Ellinghaus, David |
author_facet | Ellinghaus, David |
author_sort | Ellinghaus, David |
collection | PubMed |
description | Genome-wide association studies (GWAS) for autoimmune hepatitis (AIH) and GWAS/genome-wide meta-analyses (GWMA) for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) have been successful over the past decade, identifying about 100 susceptibility loci in the human genome, with strong associations with the HLA locus and many susceptibility variants outside the HLA locus with relatively low risk. However, identifying causative variants and genes and determining their effects on liver cells and their immunological microenvironment is far from trivial. Polygenic risk scores (PRSs) based on current genome-wide data have limited potential to predict individual disease risk. Interestingly, results of mediated expression score regression analysis provide evidence that a substantial portion of gene expression at susceptibility loci is mediated by genetic risk variants, in contrast to many other complex diseases. Genome- and transcriptome-wide comparisons between AIH, PBC, and PSC could help to better delineate the shared inherited component of autoimmune liver diseases (AILDs), and statistical fine-mapping, chromosome X-wide association testing, and genome-wide in silico drug screening approaches recently applied to GWMA data from PBC could potentially be successfully applied to AIH and PSC. Initial successes through single-cell RNA sequencing (scRNA-seq) experiments in PBC and PSC now raise high hopes for understanding the impact of genetic risk variants in the context of liver-resident immune cells and liver cell subpopulations, and for bridging the gap between genetics and disease. |
format | Online Article Text |
id | pubmed-9256578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-92565782022-07-07 How genetic risk contributes to autoimmune liver disease Ellinghaus, David Semin Immunopathol Review Genome-wide association studies (GWAS) for autoimmune hepatitis (AIH) and GWAS/genome-wide meta-analyses (GWMA) for primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) have been successful over the past decade, identifying about 100 susceptibility loci in the human genome, with strong associations with the HLA locus and many susceptibility variants outside the HLA locus with relatively low risk. However, identifying causative variants and genes and determining their effects on liver cells and their immunological microenvironment is far from trivial. Polygenic risk scores (PRSs) based on current genome-wide data have limited potential to predict individual disease risk. Interestingly, results of mediated expression score regression analysis provide evidence that a substantial portion of gene expression at susceptibility loci is mediated by genetic risk variants, in contrast to many other complex diseases. Genome- and transcriptome-wide comparisons between AIH, PBC, and PSC could help to better delineate the shared inherited component of autoimmune liver diseases (AILDs), and statistical fine-mapping, chromosome X-wide association testing, and genome-wide in silico drug screening approaches recently applied to GWMA data from PBC could potentially be successfully applied to AIH and PSC. Initial successes through single-cell RNA sequencing (scRNA-seq) experiments in PBC and PSC now raise high hopes for understanding the impact of genetic risk variants in the context of liver-resident immune cells and liver cell subpopulations, and for bridging the gap between genetics and disease. Springer Berlin Heidelberg 2022-06-01 2022 /pmc/articles/PMC9256578/ /pubmed/35650446 http://dx.doi.org/10.1007/s00281-022-00950-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Ellinghaus, David How genetic risk contributes to autoimmune liver disease |
title | How genetic risk contributes to autoimmune liver disease |
title_full | How genetic risk contributes to autoimmune liver disease |
title_fullStr | How genetic risk contributes to autoimmune liver disease |
title_full_unstemmed | How genetic risk contributes to autoimmune liver disease |
title_short | How genetic risk contributes to autoimmune liver disease |
title_sort | how genetic risk contributes to autoimmune liver disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256578/ https://www.ncbi.nlm.nih.gov/pubmed/35650446 http://dx.doi.org/10.1007/s00281-022-00950-8 |
work_keys_str_mv | AT ellinghausdavid howgeneticriskcontributestoautoimmuneliverdisease |