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A New Methodology to Associate SNPs with Human Diseases According to Their Pathway Related Context
Genome-wide association studies (GWAS) with hundreds of żthousands of single nucleotide polymorphisms (SNPs) are popular strategies to reveal the genetic basis of human complex diseases. Despite many successes of GWAS, it is well recognized that new analytical approaches have to be integrated to ach...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201947/ https://www.ncbi.nlm.nih.gov/pubmed/22046267 http://dx.doi.org/10.1371/journal.pone.0026277 |
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author | Bakir-Gungor, Burcu Sezerman, Osman Ugur |
author_facet | Bakir-Gungor, Burcu Sezerman, Osman Ugur |
author_sort | Bakir-Gungor, Burcu |
collection | PubMed |
description | Genome-wide association studies (GWAS) with hundreds of żthousands of single nucleotide polymorphisms (SNPs) are popular strategies to reveal the genetic basis of human complex diseases. Despite many successes of GWAS, it is well recognized that new analytical approaches have to be integrated to achieve their full potential. Starting with a list of SNPs, found to be associated with disease in GWAS, here we propose a novel methodology to devise functionally important KEGG pathways through the identification of genes within these pathways, where these genes are obtained from SNP analysis. Our methodology is based on functionalization of important SNPs to identify effected genes and disease related pathways. We have tested our methodology on WTCCC Rheumatoid Arthritis (RA) dataset and identified: i) previously known RA related KEGG pathways (e.g., Toll-like receptor signaling, Jak-STAT signaling, Antigen processing, Leukocyte transendothelial migration and MAPK signaling pathways); ii) additional KEGG pathways (e.g., Pathways in cancer, Neurotrophin signaling, Chemokine signaling pathways) as associated with RA. Furthermore, these newly found pathways included genes which are targets of RA-specific drugs. Even though GWAS analysis identifies 14 out of 83 of those drug target genes; newly found functionally important KEGG pathways led to the discovery of 25 out of 83 genes, known to be used as drug targets for the treatment of RA. Among the previously known pathways, we identified additional genes associated with RA (e.g. Antigen processing and presentation, Tight junction). Importantly, within these pathways, the associations between some of these additionally found genes, such as HLA-C, HLA-G, PRKCQ, PRKCZ, TAP1, TAP2 and RA were verified by either OMIM database or by literature retrieved from the NCBI PubMed module. With the whole-genome sequencing on the horizon, we show that the full potential of GWAS can be achieved by integrating pathway and network-oriented analysis and prior knowledge from functional properties of a SNP. |
format | Online Article Text |
id | pubmed-3201947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32019472011-11-01 A New Methodology to Associate SNPs with Human Diseases According to Their Pathway Related Context Bakir-Gungor, Burcu Sezerman, Osman Ugur PLoS One Research Article Genome-wide association studies (GWAS) with hundreds of żthousands of single nucleotide polymorphisms (SNPs) are popular strategies to reveal the genetic basis of human complex diseases. Despite many successes of GWAS, it is well recognized that new analytical approaches have to be integrated to achieve their full potential. Starting with a list of SNPs, found to be associated with disease in GWAS, here we propose a novel methodology to devise functionally important KEGG pathways through the identification of genes within these pathways, where these genes are obtained from SNP analysis. Our methodology is based on functionalization of important SNPs to identify effected genes and disease related pathways. We have tested our methodology on WTCCC Rheumatoid Arthritis (RA) dataset and identified: i) previously known RA related KEGG pathways (e.g., Toll-like receptor signaling, Jak-STAT signaling, Antigen processing, Leukocyte transendothelial migration and MAPK signaling pathways); ii) additional KEGG pathways (e.g., Pathways in cancer, Neurotrophin signaling, Chemokine signaling pathways) as associated with RA. Furthermore, these newly found pathways included genes which are targets of RA-specific drugs. Even though GWAS analysis identifies 14 out of 83 of those drug target genes; newly found functionally important KEGG pathways led to the discovery of 25 out of 83 genes, known to be used as drug targets for the treatment of RA. Among the previously known pathways, we identified additional genes associated with RA (e.g. Antigen processing and presentation, Tight junction). Importantly, within these pathways, the associations between some of these additionally found genes, such as HLA-C, HLA-G, PRKCQ, PRKCZ, TAP1, TAP2 and RA were verified by either OMIM database or by literature retrieved from the NCBI PubMed module. With the whole-genome sequencing on the horizon, we show that the full potential of GWAS can be achieved by integrating pathway and network-oriented analysis and prior knowledge from functional properties of a SNP. Public Library of Science 2011-10-25 /pmc/articles/PMC3201947/ /pubmed/22046267 http://dx.doi.org/10.1371/journal.pone.0026277 Text en Bakir-Gungor, Sezerman. 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 Bakir-Gungor, Burcu Sezerman, Osman Ugur A New Methodology to Associate SNPs with Human Diseases According to Their Pathway Related Context |
title | A New Methodology to Associate SNPs with Human Diseases According to Their Pathway Related Context |
title_full | A New Methodology to Associate SNPs with Human Diseases According to Their Pathway Related Context |
title_fullStr | A New Methodology to Associate SNPs with Human Diseases According to Their Pathway Related Context |
title_full_unstemmed | A New Methodology to Associate SNPs with Human Diseases According to Their Pathway Related Context |
title_short | A New Methodology to Associate SNPs with Human Diseases According to Their Pathway Related Context |
title_sort | new methodology to associate snps with human diseases according to their pathway related context |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3201947/ https://www.ncbi.nlm.nih.gov/pubmed/22046267 http://dx.doi.org/10.1371/journal.pone.0026277 |
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