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The difficulty lies in our limited understanding of how phenotypic traits arise from non-coding genetic variants in highly organized biological systems with heterogeneous gene expression across cells and tissues.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We present a novel strategy, called GWAS component analysis, for transferring disease associations from single-nucleotide polymorphisms to co-expression modules by stacking models trained using reference genome and tissue-specific gene expression data. Application of this method to genome-wide association studies of blood cell counts confirmed that it could detect gene sets enriched in expected cell types. In addition, coupling of our method with Bayesian networks enables GWAS components to be used to discover drug targets.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We tested genome-wide associations of four disease phenotypes, including age-related macular degeneration, Crohn\u2019s disease, ulcerative colitis and rheumatoid arthritis, and demonstrated the proposed method could select more functional genes than S-PrediXcan, the previous single-step model for predicting gene-level associations from SNP-level associations.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13040-020-00216-9","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T12:02:58Z","timestamp":1592395378000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of therapeutic targets from genetic association studies using hierarchical component analysis"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1538-6175","authenticated-orcid":false,"given":"Hao-Chih","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Ichikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin S.","family":"Glicksberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aparna A.","family":"Divaraniya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine E.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pankaj","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel T.","family":"Dudley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,6,17]]},"reference":[{"issue":"5507","key":"216_CR1","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1126\/science.1058040","volume":"291","author":"JC Venter","year":"2001","unstructured":"Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, et al. 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