A Novel Statistic for Genome-Wide Interaction Analysis
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{"title"=>"A Novel Statistic for Genome-wide interaction analysis", "type"=>"journal", "authors"=>[{"first_name"=>"Xuesen", "last_name"=>"Wu", "scopus_author_id"=>"24167124900"}, {"first_name"=>"Hua", "last_name"=>"Dong", "scopus_author_id"=>"55460764600"}, {"first_name"=>"Li", "last_name"=>"Luo", "scopus_author_id"=>"57199078157"}, {"first_name"=>"Yun", "last_name"=>"Zhu", "scopus_author_id"=>"55367584800"}, {"first_name"=>"Gang", "last_name"=>"Peng", "scopus_author_id"=>"35278876400"}, {"first_name"=>"John D.", "last_name"=>"Reveille", "scopus_author_id"=>"35355292100"}, {"first_name"=>"Momiao", "last_name"=>"Xiong", "scopus_author_id"=>"7102692781"}], "year"=>2010, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "pui"=>"359882456", "sgr"=>"78049425657", "doi"=>"10.1371/journal.pgen.1001131", "scopus"=>"2-s2.0-78049425657", "pmid"=>"20885795"}, "id"=>"5a18e261-fd94-3c23-8bd2-165d7aa5ed52", "abstract"=>"It is expected that genome-wide interaction analysis can be a possible source of finding heritability unexplained by current GWAS. However, the existing statistics for testing interaction have low power for genome-wide interaction analysis. To meet challenges raised by genome-wide interactional analysis, we develop a novel statistic for testing interaction between two loci (either linked or unlinked) and validate the null distribution and the type I error rates of the new statistic through simulations. By extensive power studies we show that the developed novel statistic has much higher power to detect interaction than the classical logistic regression. To provide evidence of gene–gene interactions as a possible source of the missing heritability unexplained by the current GWAS, we performed the genome-wide interaction analysis of psoriasis in two independent studies. The preliminary results identified 44 and 211 pairs of SNPs showing significant evidence of interactions with FDR<0.001 and 0.001<FDR<0.003, respectively, which were common in two independent studies. These included five interacting pairs of SNPs, some of which were located in the target sites: LST1/NCR3, CXCR5/BCL9L and GLS2 of miR-324-3p, miR-433, and miR-382, and 15 pairs of interacting SNPs that had nonsynonymous substitutions.", "link"=>"http://www.mendeley.com/research/novel-statistic-genomewide-interaction-analysis", "reader_count"=>105, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>14, "Researcher"=>27, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>36, "Student > Postgraduate"=>3, "Student > Master"=>7, "Other"=>2, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>11}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>14, "Researcher"=>27, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>36, "Student > Postgraduate"=>3, "Student > Master"=>7, "Other"=>2, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>11}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>8, "Mathematics"=>4, "Agricultural and Biological Sciences"=>62, "Medicine and Dentistry"=>15, "Neuroscience"=>1, "Computer Science"=>9}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>15}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>62}, "Computer Science"=>{"Computer Science"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>8}, "Mathematics"=>{"Mathematics"=>4}, "Unspecified"=>{"Unspecified"=>5}}, "reader_count_by_country"=>{"Netherlands"=>1, "Austria"=>1, "Belgium"=>1, "United States"=>10, "Denmark"=>1, "Australia"=>1, "Switzerland"=>1, "Germany"=>2, "Indonesia"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/828557"], "description"=>"<p>Each pathway was represented by an ellipse with the number. The SNPs were\n represented by nodes and placed insight their located pathways. Nearby\n each SNP there was its RS number and the name of its located gene. The\n pathway and its harbored SNPs were labeled by the same color. The\n interacting SNPs were connected by the solid light green lines.</p>", "links"=>[], "tags"=>["snps", "located", "19", "pathways", "formed", "a"], "article_id"=>498917, "categories"=>["Genetics"], "users"=>["Xuesen Wu", "Hua Dong", "Li Luo", "Yun Zhu", "Gang Peng", "John D. Reveille", "Momiao Xiong"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001131.g006", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Interacting_SNPs_that_were_located_in_19_pathways_formed_a____network_/498917", "title"=>"Interacting SNPs that were located in 19 pathways formed a\n network.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-23 02:28:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/828472"], "description"=>"<p>(A) The power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression analysis\n for testing interaction between two unlinked loci as a function of\n traditional odds-ratio under a\n two-locus recessiverecessive\n disease model, where the number of individuals in both the case and\n control groups is 2,000, the significance level is 0.001, and the\n odds-ratios at two loci were . (B) The\n power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression analysis\n for testing interaction between two unlinked loci as a function of\n traditional odds-ratio under a\n two-locus dominantdominant\n disease model, where the number of individuals in both the case and\n control groups is 1,000, the significance level is 0.001, and the\n odds-ratios at two loci were . (C) The\n power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression analysis\n for testing interaction between two unlinked loci as a function of\n traditional odds-ratio under a\n two-locus additiveadditive\n disease model, where the number of individuals in both the case and\n control groups is 1,000, the significance level is 0.001, and the\n odds-ratios at two loci were .</p>", "links"=>[], "tags"=>["unlinked"], "article_id"=>498838, "categories"=>["Genetics"], "users"=>["Xuesen Wu", "Hua Dong", "Li Luo", "Yun Zhu", "Gang Peng", "John D. Reveille", "Momiao Xiong"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001131.g005", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Power_of_the_statistics_for_testing_interaction_between_two_unlinked____loci_/498838", "title"=>"Power of the statistics for testing interaction between two unlinked\n loci.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-23 02:27:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/828410"], "description"=>"<p>(A) The power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression for\n testing interaction between two linked loci analysis as a function of\n traditional odds-ratio under a\n two-locus additiveadditive\n disease model, where the number of individuals in both the case and\n control groups is 1,000, the significance level is 0.05, and the\n odds-ratios at two loci were . (B) The\n power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression for\n testing interaction between two linked loci analysis as a function of\n traditional odds-ratio under a\n two-locus additiveadditive\n disease model, where the number of individuals in both the case and\n control groups is 1,000, the significance level is 0.01, and the\n odds-ratios at two loci were . (C) The\n power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression for\n testing interaction between two linked loci analysis as a function of\n traditional odds-ratio under a\n two-locus additiveadditive\n disease model, where the number of individuals in both the case and\n control groups is 1,000, the significance level is 0.001, and the\n odds-ratios at two loci were .</p>", "links"=>[], "tags"=>["linked", "loci", "additive"], "article_id"=>498775, "categories"=>["Genetics"], "users"=>["Xuesen Wu", "Hua Dong", "Li Luo", "Yun Zhu", "Gang Peng", "John D. Reveille", "Momiao Xiong"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001131.g004", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Power_of_the_statistics_for_testing_interaction_between_two_linked____loci_under_additive_disease_model_/498775", "title"=>"Power of the statistics for testing interaction between two linked\n loci under additive disease model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-23 02:26:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/412404", "https://ndownloader.figshare.com/files/412412", "https://ndownloader.figshare.com/files/412422", "https://ndownloader.figshare.com/files/412438", "https://ndownloader.figshare.com/files/412455"], "description"=>"<div><p>Although great progress in genome-wide association studies (GWAS) has been made, the significant SNP associations identified by GWAS account for only a few percent of the genetic variance, leading many to question where and how we can find the missing heritability. There is increasing interest in genome-wide interaction analysis as a possible source of finding heritability unexplained by current GWAS. However, the existing statistics for testing interaction have low power for genome-wide interaction analysis. To meet challenges raised by genome-wide interactional analysis, we have developed a novel statistic for testing interaction between two loci (either linked or unlinked). The null distribution and the type I error rates of the new statistic for testing interaction are validated using simulations. Extensive power studies show that the developed statistic has much higher power to detect interaction than classical logistic regression. The results identified 44 and 211 pairs of SNPs showing significant evidence of interactions with FDR<0.001 and 0.001 </p></div>", "links"=>[], "tags"=>["statistic", "genome-wide", "interaction"], "article_id"=>141465, "categories"=>["Genetics"], "users"=>["Xuesen Wu", "Hua Dong", "Li Luo", "Yun Zhu", "Gang Peng", "John D. Reveille", "Momiao Xiong"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1001131.s001", "https://dx.doi.org/10.1371/journal.pgen.1001131.s002", "https://dx.doi.org/10.1371/journal.pgen.1001131.s003", "https://dx.doi.org/10.1371/journal.pgen.1001131.s004", "https://dx.doi.org/10.1371/journal.pgen.1001131.s005"], "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Novel_Statistic_for_Genome_Wide_Interaction___Analysis/141465", "title"=>"A Novel Statistic for Genome-Wide Interaction\n Analysis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-09-23 00:24:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/828256"], "description"=>"<p>(A) The power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression analysis\n for testing interaction between two linked loci as a function of\n traditional odds-ratio under a\n two-locus recessiverecessive\n disease model, where the number of individuals in both the case and\n control groups is 2,000, the significance level is 0.05, and the\n odds-ratios at two loci were . (B) The\n power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression analysis\n for testing interaction between two linked loci as a function of\n traditional odds-ratio under a\n two-locus recessiverecessive\n disease model, where the number of individuals in both the case and\n control groups is 2,000, the significance level is 0.01, and the\n odds-ratios at two loci were . (C) The\n power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression analysis\n for testing interaction between two linked loci as a function of\n traditional odds-ratio under a\n two-locus recessiverecessive\n disease model, where the number of individuals in both the case and\n control groups is 2,000, the significance level is 0.001, and the\n odds-ratios at two loci were .</p>", "links"=>[], "tags"=>["linked", "loci", "recessive"], "article_id"=>498621, "categories"=>["Genetics"], "users"=>["Xuesen Wu", "Hua Dong", "Li Luo", "Yun Zhu", "Gang Peng", "John D. Reveille", "Momiao Xiong"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001131.g002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Power_of_the_statistics_for_testing_interaction_between_two_linked____loci_under_recessive_disease_model_/498621", "title"=>"Power of the statistics for testing interaction between two linked\n loci under recessive disease model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-23 02:23:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/828319"], "description"=>"<p>(A) The power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression analysis\n for testing interaction between two linked loci as a function of\n traditional odds-ratio under a\n two-locus dominantdominant\n disease model, where the number of individuals in both the case and\n control groups is 1,000, the significance level is 0.05, and the\n odds-ratios at two loci were . (B) The\n power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression analysis\n for testing interaction between two linked loci as a function of\n traditional odds-ratio under a\n two-locus dominantdominant\n disease model, where the number of individuals in both the case and\n control groups is 1,000, the significance level is 0.01, and the\n odds-ratios at two loci were . (C) The\n power of the test statistic , the\n “fast-epistasis” in PLINK and logistic regression analysis\n for testing interaction between two linked loci as a function of\n traditional odds-ratio under a\n two-locus dominantdominant\n disease model, where the number of individuals in both the case and\n control groups is 1,000, the significance level is 0.001, and the\n odds-ratios at two loci were .</p>", "links"=>[], "tags"=>["linked", "loci"], "article_id"=>498686, "categories"=>["Genetics"], "users"=>["Xuesen Wu", "Hua Dong", "Li Luo", "Yun Zhu", "Gang Peng", "John D. Reveille", "Momiao Xiong"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001131.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Power_of_the_statistics_for_testing_interaction_between_two_linked____loci_under_dominant_disease_model_/498686", "title"=>"Power of the statistics for testing interaction between two linked\n loci under dominant disease model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-23 02:24:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/828185"], "description"=>"<p>(A) Quantile-quantile plots for the test statistic\n in dataset\n 1. The P-values (<) for the\n test are plotted (as −log10 values) as a function of its expected\n p values. (B) Quantile-quantile plots for the test statistic\n in dataset\n 2. The P-values (<) for the\n test are plotted (as −log10 values) as a function of its expected\n p values.</p>", "links"=>[], "tags"=>["plots", "statistic"], "article_id"=>498549, "categories"=>["Genetics"], "users"=>["Xuesen Wu", "Hua Dong", "Li Luo", "Yun Zhu", "Gang Peng", "John D. Reveille", "Momiao Xiong"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1001131.g001", "stats"=>{"downloads"=>9, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantile_quantile_plots_for_the_test_statistic_____/498549", "title"=>"Quantile-quantile plots for the test statistic\n .", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-09-23 02:22:29"}

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