{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:36:34Z","timestamp":1785278194307,"version":"3.55.0"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T00:00:00Z","timestamp":1574812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Over the last 10\u2009years, there have been over 3300 genome-wide association studies (GWAS). Almost every GWAS study provides a Manhattan plot either as a main figure or in the supplement. Several software packages can generate a Manhattan plot, but they are all limited in the extent to which they can annotate gene-names, allele frequencies, and variants having high impact on gene function or provide any other added information or flexibility. Furthermore, in a conventional Manhattan plot, there is no way of distinguishing a locus identified due to a single variant with very significant <jats:italic>p<\/jats:italic>-value from a locus with multiple variants which appear to be in a haplotype block having very similar <jats:italic>p<\/jats:italic>-values.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Here we present a software tool written in R, which generates a transposed Manhattan plot along with additional features like variant consequence and minor allele frequency to annotate the plot and addresses these limitations. The software also gives flexibility on how and where the user wants to display the annotations. The software can be downloaded from CRAN repository and also from the GitHub project page.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We present a major step up to the existing conventional Manhattan plot generation tools. We hope this form of display along with the added annotations will bring more insight to the reader from this new Manhattan++ plot.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12859-019-3201-y","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T16:02:56Z","timestamp":1574870576000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Manhattan++: displaying genome-wide association summary statistics with multiple annotation layers"],"prefix":"10.1186","volume":"20","author":[{"given":"Christopher","family":"Grace","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Farrall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Watkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2307-4021","authenticated-orcid":false,"given":"Anuj","family":"Goel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,27]]},"reference":[{"issue":"25","key":"3201_CR1","doi-asserted-by":"publisher","first-page":"731","DOI":"10.21105\/joss.00731","volume":"3","author":"SD Turner","year":"2018","unstructured":"Turner SD. Qqman: an R package for visualizing GWAS results using Q-Q and Manhattan plots. J Open Source Softw. 2018;3(25):731\u20132.","journal-title":"J Open Source Softw"},{"key":"3201_CR2","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1186\/1471-2105-11-288","volume":"11","author":"R Magi","year":"2010","unstructured":"Magi R, Morris AP. GWAMA: software for genome-wide association meta-analysis. BMC bioinformatics. 2010;11:288.","journal-title":"BMC bioinformatics."},{"issue":"2","key":"3201_CR3","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1093\/bib\/bbs017","volume":"14","author":"H Thorvaldsdottir","year":"2013","unstructured":"Thorvaldsdottir H, Robinson JT, Mesirov JP. Integrative genomics viewer (IGV): high-performance genomics data visualization and exploration. 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Genetic analysis of over one million people identifies 535 novel loci for blood pressure. bioRxiv. 2017.","DOI":"10.1097\/01.hjh.0000539644.13726.3b"},{"issue":"7359","key":"3201_CR6","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/nature10251","volume":"476","author":"S Sawcer","year":"2011","unstructured":"International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium, Sawcer S, Hellenthal G, Pirinen M, Spencer CC, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214\u20139.","journal-title":"Nature."},{"issue":"12","key":"3201_CR7","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.1093\/hmg\/dds099","volume":"21","author":"JE Martin","year":"2012","unstructured":"Martin JE, Broen JC, Carmona FD, Teruel M, Simeon CP, Vonk MC, et al. Identification of CSK as a systemic sclerosis genetic risk factor through genome wide association study follow-up. 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J Am Coll Cardiol. 2016;68(13):1435\u201348.","journal-title":"J Am Coll Cardiol"},{"issue":"9","key":"3201_CR10","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1038\/ng.3913","volume":"49","author":"CP Nelson","year":"2017","unstructured":"Nelson CP, Goel A, Butterworth AS, Kanoni S, Webb TR, Marouli E, et al. Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nat Genet. 2017;49(9):1385\u201391.","journal-title":"Nat Genet"},{"key":"3201_CR11","doi-asserted-by":"crossref","unstructured":"Cortes A, Dendrou CA, Fugger L, McVean G. Systematic classification of shared components of genetic risk for common human diseases. BioRxiv. 2018.","DOI":"10.1101\/374207"}],"container-title":["BMC Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-3201-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12859-019-3201-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12859-019-3201-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T00:17:52Z","timestamp":1606349872000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbioinformatics.biomedcentral.com\/articles\/10.1186\/s12859-019-3201-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,27]]},"references-count":11,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["3201"],"URL":"https:\/\/doi.org\/10.1186\/s12859-019-3201-y","relation":{},"ISSN":["1471-2105"],"issn-type":[{"value":"1471-2105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,27]]},"assertion":[{"value":"11 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"None.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"610"}}