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Autoimmune Disease Classification by Inverse Association with SNP Alleles
With multiple genome-wide association studies (GWAS) performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorp...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791168/ https://www.ncbi.nlm.nih.gov/pubmed/20041220 http://dx.doi.org/10.1371/journal.pgen.1000792 |
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author | Sirota, Marina Schaub, Marc A. Batzoglou, Serafim Robinson, William H. Butte, Atul J. |
author_facet | Sirota, Marina Schaub, Marc A. Batzoglou, Serafim Robinson, William H. Butte, Atul J. |
author_sort | Sirota, Marina |
collection | PubMed |
description | With multiple genome-wide association studies (GWAS) performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with multiple SNPs in an allele-specific fashion. We apply this method to compare genetic variation profiles of six autoimmune diseases: multiple sclerosis (MS), ankylosing spondylitis (AS), autoimmune thyroid disease (ATD), rheumatoid arthritis (RA), Crohn's disease (CD), and type 1 diabetes (T1D), as well as five non-autoimmune diseases. We quantify pair-wise relationships between these diseases and find two broad clusters of autoimmune disease where SNPs that make an individual susceptible to one class of autoimmune disease also protect from diseases in the other autoimmune class. We find that RA and AS form one such class, and MS and ATD another. We identify specific SNPs and genes with opposite risk profiles for these two classes. We furthermore explore individual SNPs that play an important role in defining similarities and differences between disease pairs. We present a novel, systematic, cross-platform approach to identify allele-specific relationships between disease pairs based on genetic variation as well as the individual SNPs which drive the relationships. While recognizing similarities between diseases might lead to identifying novel treatment options, detecting differences between diseases previously thought to be similar may point to key novel disease-specific genes and pathways. |
format | Text |
id | pubmed-2791168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27911682009-12-30 Autoimmune Disease Classification by Inverse Association with SNP Alleles Sirota, Marina Schaub, Marc A. Batzoglou, Serafim Robinson, William H. Butte, Atul J. PLoS Genet Research Article With multiple genome-wide association studies (GWAS) performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with multiple SNPs in an allele-specific fashion. We apply this method to compare genetic variation profiles of six autoimmune diseases: multiple sclerosis (MS), ankylosing spondylitis (AS), autoimmune thyroid disease (ATD), rheumatoid arthritis (RA), Crohn's disease (CD), and type 1 diabetes (T1D), as well as five non-autoimmune diseases. We quantify pair-wise relationships between these diseases and find two broad clusters of autoimmune disease where SNPs that make an individual susceptible to one class of autoimmune disease also protect from diseases in the other autoimmune class. We find that RA and AS form one such class, and MS and ATD another. We identify specific SNPs and genes with opposite risk profiles for these two classes. We furthermore explore individual SNPs that play an important role in defining similarities and differences between disease pairs. We present a novel, systematic, cross-platform approach to identify allele-specific relationships between disease pairs based on genetic variation as well as the individual SNPs which drive the relationships. While recognizing similarities between diseases might lead to identifying novel treatment options, detecting differences between diseases previously thought to be similar may point to key novel disease-specific genes and pathways. Public Library of Science 2009-12-24 /pmc/articles/PMC2791168/ /pubmed/20041220 http://dx.doi.org/10.1371/journal.pgen.1000792 Text en Sirota et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sirota, Marina Schaub, Marc A. Batzoglou, Serafim Robinson, William H. Butte, Atul J. Autoimmune Disease Classification by Inverse Association with SNP Alleles |
title | Autoimmune Disease Classification by Inverse Association with SNP Alleles |
title_full | Autoimmune Disease Classification by Inverse Association with SNP Alleles |
title_fullStr | Autoimmune Disease Classification by Inverse Association with SNP Alleles |
title_full_unstemmed | Autoimmune Disease Classification by Inverse Association with SNP Alleles |
title_short | Autoimmune Disease Classification by Inverse Association with SNP Alleles |
title_sort | autoimmune disease classification by inverse association with snp alleles |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2791168/ https://www.ncbi.nlm.nih.gov/pubmed/20041220 http://dx.doi.org/10.1371/journal.pgen.1000792 |
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