Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression
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{"title"=>"Pathway-Based analysis of a Melanoma Genome-Wide association study: Analysis of genes related to Tumour-Immunosuppression", "type"=>"journal", "authors"=>[{"first_name"=>"Nils", "last_name"=>"Schoof", "scopus_author_id"=>"24923942700"}, {"first_name"=>"Mark M.", "last_name"=>"Iles", "scopus_author_id"=>"6701331394"}, {"first_name"=>"D. Timothy", "last_name"=>"Bishop", "scopus_author_id"=>"35354474200"}, {"first_name"=>"Julia A.", "last_name"=>"Newton-Bishop", "scopus_author_id"=>"56262799800"}, {"first_name"=>"Jennifer H.", "last_name"=>"Barrett", "scopus_author_id"=>"7403498817"}, {"last_name"=>"GenoMEL consortium", "scopus_author_id"=>"54792763400"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"363155946", "sgr"=>"84455172956", "doi"=>"10.1371/journal.pone.0029451", "scopus"=>"2-s2.0-84455172956", "pmid"=>"22216283"}, "id"=>"82114f74-8693-3cae-bc2b-1648969d5fad", "abstract"=>"Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating a priori knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (p(emp)=0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (p(emp)=0.006) and secretion of suppressive factors (p(emp)=0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.", "link"=>"http://www.mendeley.com/research/pathwaybased-analysis-melanoma-genomewide-association-study-analysis-genes-related-tumourimmunosuppr-1", "reader_count"=>11, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Student > Master"=>1, "Student > Bachelor"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>4, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Computer Science"=>{"Computer Science"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1, "France"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/698230"], "description"=>"<p>Number of SNPs in the gene region, number of SNPs with a p-value below 0.05 and the minimal p-value of the SNPs (logistic regression analysis) in the gene region are shown.</p>", "links"=>[], "tags"=>["subgroup", "secreted", "immunosuppressive"], "article_id"=>368617, "categories"=>["Developmental Biology", "Mathematics", "Biotechnology", "Immunology", "Cancer", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Nils Schoof", "Mark M. Iles", "D. Timothy Bishop", "Julia A. Newton-Bishop", "Jennifer H. Barrett", "GenoMEL consortium"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029451.t003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Detailed_results_for_the_subgroup_of_secreted_immunosuppressive_factors_/368617", "title"=>"Detailed results for the subgroup of secreted immunosuppressive factors.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-12-27 02:23:37"}
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  • {"files"=>["https://ndownloader.figshare.com/files/698179"], "description"=>"<p>Selected genes included into the analysis and division into subgroups.</p>", "links"=>[], "tags"=>["genes", "included"], "article_id"=>368577, "categories"=>["Developmental Biology", "Mathematics", "Biotechnology", "Immunology", "Cancer", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Nils Schoof", "Mark M. Iles", "D. Timothy Bishop", "Julia A. Newton-Bishop", "Jennifer H. Barrett", "GenoMEL consortium"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029451.t001", "stats"=>{"downloads"=>3, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Selected_genes_included_into_the_analysis_and_division_into_subgroups_/368577", "title"=>"Selected genes included into the analysis and division into subgroups.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-12-27 02:22:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/698138"], "description"=>"<p>1450 melanoma cases and 4047 controls were included in the analysis. Empirical p-values established by 1000 in-cluster (GenoMEL regional groups: Israel, Italy, France, Poland, Scandinavia, Spain, UK/Netherlands) label permutations are shown for the pathway statistics SUMSTAT and SUMSQ.</p>", "links"=>[], "tags"=>["replicate", "pathway", "genomel", "gwa"], "article_id"=>368521, "categories"=>["Developmental Biology", "Mathematics", "Biotechnology", "Immunology", "Cancer", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Nils Schoof", "Mark M. Iles", "D. Timothy Bishop", "Julia A. Newton-Bishop", "Jennifer H. Barrett", "GenoMEL consortium"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029451.t004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Attempt_to_replicate_the_results_of_the_pathway_analysis_in_the_second_phase_of_data_from_the_GenoMEL_GWA_study_/368521", "title"=>"Attempt to replicate the results of the pathway analysis in the second phase of data from the GenoMEL GWA study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-12-27 02:22:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/354988"], "description"=>"<div><p>Systemic immunosuppression is a risk factor for melanoma, and sunburn-induced immunosuppression is thought to be causal. Genes in immunosuppression pathways are therefore candidate melanoma-susceptibility genes. If variants within these genes individually have a small effect on disease risk, the association may be undetected in genome-wide association (GWA) studies due to low power to reach a high significance level. Pathway-based approaches have been suggested as a method of incorporating <em>a priori</em> knowledge into the analysis of GWA studies. In this study, the association of 1113 single nucleotide polymorphisms (SNPs) in 43 genes (39 genomic regions) related to immunosuppression have been analysed using a gene-set approach in 1539 melanoma cases and 3917 controls from the GenoMEL consortium GWA study. The association between melanoma susceptibility and the whole set of tumour-immunosuppression genes, and also predefined functional subgroups of genes, was considered. The analysis was based on a measure formed by summing the evidence from the most significant SNP in each gene, and significance was evaluated empirically by case-control label permutation. An association was found between melanoma and the complete set of genes (p<sub>emp</sub> = 0.002), as well as the subgroups related to the generation of tolerogenic dendritic cells (p<sub>emp</sub> = 0.006) and secretion of suppressive factors (p<sub>emp</sub> = 0.0004), thus providing preliminary evidence of involvement of tumour-immunosuppression gene polymorphisms in melanoma susceptibility. The analysis was repeated on a second phase of the GenoMEL study, which showed no evidence of an association. As one of the first attempts to replicate a pathway-level association, our results suggest that low power and heterogeneity may present challenges.</p> </div>", "links"=>[], "tags"=>["pathway-based", "melanoma", "genome-wide", "genes", "tumour-immunosuppression"], "article_id"=>130151, "categories"=>["Developmental Biology", "Mathematics", "Biotechnology", "Immunology", "Cancer", "Biological Sciences", "Genetics", "Evolutionary Biology"], "users"=>["Nils Schoof", "Mark M. Iles", "D. Timothy Bishop", "Julia A. Newton-Bishop", "Jennifer H. Barrett", "GenoMEL consortium"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029451", "stats"=>{"downloads"=>7, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Pathway_Based_Analysis_of_a_Melanoma_Genome_Wide_Association_Study_Analysis_of_Genes_Related_to_Tumour_Immunosuppression/130151", "title"=>"Pathway-Based Analysis of a Melanoma Genome-Wide Association Study: Analysis of Genes Related to Tumour-Immunosuppression", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-12-27 00:02:31"}

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Relative Metric

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