{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,4]],"date-time":"2024-08-04T02:35:24Z","timestamp":1722738924360},"reference-count":14,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,10,12]],"date-time":"2016-10-12T00:00:00Z","timestamp":1476230400000},"content-version":"vor","delay-in-days":377,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: To increase detection power, gene level analysis methods are used to aggregate weak signals. To greatly increase computational efficiency, most methods use as input summary statistics from genome-wide association studies (GWAS). Subsequently, gene statistics are constructed using linkage disequilibrium (LD) patterns from a relevant reference panel. However, all methods, including our own Joint Effect on Phenotype of eQTL\/functional single nucleotide polymorphisms (SNPs) associated with a Gene (JEPEG), assume homogeneous panels, e.g. European. However, this renders these tools unsuitable for the analysis of large cosmopolitan cohorts.<\/jats:p>\n               <jats:p>Results: We propose a JEPEG extension, JEPEGMIX, which similar to one of our software tools, Direct Imputation of summary STatistics of unmeasured SNPs from MIXed ethnicity cohorts, is capable of estimating accurate LD patterns for cosmopolitan cohorts. JEPEGMIX uses this accurate LD estimates to (i) impute the summary statistics at unmeasured functional variants and (ii) test for the joint effect of all measured and imputed functional variants which are associated with a gene. We illustrate the performance of our tool by analyzing the GWAS meta-analysis summary statistics from the multi-ethnic Psychiatric Genomics Consortium Schizophrenia stage 2 cohort. This practical application supports the immune system being one of the main drivers of the process leading to schizophrenia.<\/jats:p>\n               <jats:p>Availability and implementation: Software, annotation database and examples are available at http:\/\/dleelab.github.io\/jepegmix\/.<\/jats:p>\n               <jats:p>Contact: \u00a0donghyung.lee@vcuhealth.org<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary material is available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv567","type":"journal-article","created":{"date-parts":[[2015,10,2]],"date-time":"2015-10-02T01:44:04Z","timestamp":1443750244000},"page":"295-297","source":"Crossref","is-referenced-by-count":9,"title":["JEPEGMIX: gene-level joint analysis of functional SNPs in cosmopolitan cohorts"],"prefix":"10.1093","volume":"32","author":[{"given":"Donghyung","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vernell S.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. Bernard","family":"Bigdeli","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brien P.","family":"Riley","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley T.","family":"Webb","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayman H.","family":"Fanous","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth S.","family":"Kendler","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir I.","family":"Vladimirov","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silviu-Alin","family":"Bacanu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,10,1]]},"reference":[{"key":"2023020110281715100_btv567-B1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/nature09534","article-title":"A map of human genome variation from population-scale sequencing","volume":"467","author":"Altshuler","year":"2010","journal-title":"Nature"},{"key":"2023020110281715100_btv567-B2","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","article-title":"Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls","volume":"447","author":"Burton","year":"2007","journal-title":"Nature"},{"key":"2023020110281715100_btv567-B3","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/j.ajhg.2012.09.013","article-title":"A multi-SNP locus-association method reveals a substantial fraction of the missing heritability","volume":"91","author":"Ehret","year":"2012","journal-title":"Am. 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Genet."},{"key":"2023020110281715100_btv567-B4","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1093\/bioinformatics\/btt500","article-title":"DIST: direct imputation of summary statistics for unmeasured SNPs","volume":"29","author":"Lee","year":"2013","journal-title":"Bioinformatics"},{"key":"2023020110281715100_btv567-B5","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1093\/bioinformatics\/btv348","article-title":"DISTMIX: direct imputation of summary statistics for unmeasured SNPs from mixed ethnicity cohorts","volume":"31","author":"Lee","year":"2015","journal-title":"Bioinformatics"},{"key":"2023020110281715100_btv567-B6","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1093\/bioinformatics\/btu816","article-title":"JEPEG: a summary statistics based tool for gene-level joint testing of functional variants","volume":"31","author":"Lee","year":"2015","journal-title":"Bioinformatics"},{"key":"2023020110281715100_btv567-B7","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/nature08494","article-title":"Finding the missing heritability of complex diseases","volume":"461","author":"Manolio","year":"2009","journal-title":"Nature"},{"key":"2023020110281715100_btv567-B8","doi-asserted-by":"crossref","first-page":"i181","DOI":"10.1093\/bioinformatics\/btv230","article-title":"Adapt-Mix: learning local genetic correlation structure improves summary statistics-based analyses","volume":"31","author":"Park","year":"2015","journal-title":"Bioinformatics"},{"key":"2023020110281715100_btv567-B9","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1093\/bioinformatics\/btu416","article-title":"Fast and accurate imputation of summary statistics enhances evidence of functional enrichment","volume":"30","author":"Pasaniuc","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020110281715100_btv567-B10","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nature13595","article-title":"Biological insights from 108 schizophrenia-associated genetic loci","volume":"511","author":"Schizophrenia Working Group of the Psychiatric Genomics Consortium","year":"2014","journal-title":"Nature"},{"key":"2023020110281715100_btv567-B11","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1093\/hmg\/ddr328","article-title":"Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association","volume":"20","author":"Wood","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"2023020110281715100_btv567-B12","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1093\/bioinformatics\/btv168","article-title":"DISSCO: direct imputation of summary statistics allowing covariates","volume":"31","author":"Xu","year":"2015","journal-title":"Bioinformatics"},{"key":"2023020110281715100_btv567-B13","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/ng.608","article-title":"Common SNPs explain a large proportion of the heritability for human height","volume":"42","author":"Yang","year":"2010","journal-title":"Nat. Genet."},{"key":"2023020110281715100_btv567-B14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ng.2213","article-title":"Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits","volume":"44","author":"Yang","year":"2012","journal-title":"Nat. Genet."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/2\/295\/49016375\/bioinformatics_32_2_295.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/2\/295\/49016375\/bioinformatics_32_2_295.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T21:36:10Z","timestamp":1675287370000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/32\/2\/295\/1744366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10,1]]},"references-count":14,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,1,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btv567","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2016,1,15]]},"published":{"date-parts":[[2015,10,1]]}}}