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A substantial fraction of these identified loci is associated with multiple traits\u2014a phenomena known as pleiotropy. Identification of pleiotropic associations can help characterize the genetic relationship among complex traits and can facilitate our understanding of disease etiology. Effective pleiotropic association mapping requires the development of statistical methods that can jointly model multiple traits with genome-wide single nucleic polymorphisms (SNPs) together.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We develop a joint modeling method, which we refer to as the integrative MApping of Pleiotropic association (iMAP). iMAP models summary statistics from GWASs, uses a multivariate Gaussian distribution to account for phenotypic correlation, simultaneously infers genome-wide SNP association pattern using mixture modeling and has the potential to reveal causal relationship between traits. Importantly, iMAP integrates a large number of SNP functional annotations to substantially improve association mapping power, and, with a sparsity-inducing penalty, is capable of selecting informative annotations from a large, potentially non-informative set. To enable scalable inference of iMAP to association studies with hundreds of thousands of individuals and millions of SNPs, we develop an efficient expectation maximization algorithm based on an approximate penalized regression algorithm. With simulations and comparisons to existing methods, we illustrate the benefits of iMAP in terms of both high association mapping power and accurate estimation of genome-wide SNP association patterns. Finally, we apply iMAP to perform a joint analysis of 48 traits from 31 GWAS consortia together with 40 tissue-specific SNP annotations generated from the Roadmap Project.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>iMAP is freely available at http:\/\/www.xzlab.org\/software.html.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty204","type":"journal-article","created":{"date-parts":[[2018,4,2]],"date-time":"2018-04-02T23:19:15Z","timestamp":1522711155000},"page":"2797-2807","source":"Crossref","is-referenced-by-count":32,"title":["Pleiotropic mapping and annotation selection in genome-wide association studies with penalized Gaussian mixture models"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2710-3440","authenticated-orcid":false,"given":"Ping","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Xuzhou Medical University, Xuzhou, Jiangsu, China"},{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"},{"name":"Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingjie","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"},{"name":"Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"},{"name":"Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,4,4]]},"reference":[{"key":"2023012712585178200_bty204-B1","volume-title":"Current Protocols in Human Genetics","author":"Adzhubei","year":"2013"},{"key":"2023012712585178200_bty204-B2","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1161\/HYPERTENSIONAHA.113.02077","article-title":"Identifying common genetic variants in blood pressure due to polygenic pleiotropy with associated phenotypes","volume":"63","author":"Andreassen","year":"2014","journal-title":"Hypertension"},{"key":"2023012712585178200_bty204-B3","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1534\/genetics.115.178616","article-title":"Characterizing race\/ethnicity and genetic ancestry for 100,000 subjects in the genetic epidemiology research on adult health and aging (GERA) cohort","volume":"200","author":"Banda","year":"2015","journal-title":"Genetics"},{"key":"2023012712585178200_bty204-B4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. 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