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Specifically, we employ the intersection\u2013union test approach combined with the likelihood ratio test to detect mediation effect of multiple genetic variants via some mediator (e.g., the expression of a neighboring gene) on outcome. We fit high\u2010dimensional generalized linear mixed models under the mediation framework, separately under the null and alternative hypothesis. We leverage Laplace approximation to compute the marginal likelihood of outcome and use coordinate descent algorithm to estimate corresponding parameters. Our extensive simulations demonstrate the validity of our proposed methods and substantial, up to 97%, power gains over alternative methods. Applications to real data for the study of\n                    <jats:italic>Chlamydia trachomatis<\/jats:italic>\n                    infection further showcase advantages of our methods. We believe our proposed methods will be of value and general interest in this post\u2010GWAS era to disentangle the potential causal mechanism from DNA to phenotype for new drug discovery and personalized\u00a0medicine.\n                  <\/jats:p>","DOI":"10.1111\/biom.13418","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:11:13Z","timestamp":1607991073000},"page":"364-375","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Generalized multi\u2010SNP mediation intersection\u2013union test"],"prefix":"10.1093","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6824-2255","authenticated-orcid":false,"given":"Wujuan","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Biostatistics The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toni","family":"Darville","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"},{"name":"Department of Pediatrics The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Fine","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"},{"name":"Department of Statistics and Operations Research The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9275-4189","authenticated-orcid":false,"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"},{"name":"Department of Genetics The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"},{"name":"Department of Computer Science The University of North Carolina at Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,1,13]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"45","article-title":"Host genetic contribution to the cellular immune response to Chlamydia trachomatis: heritability estimate from a Gambian twin study","volume":"45","author":"Bailey R.","year":"2009","journal-title":"Drugs of Today (Barcelona, Spain: 1998)"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1037\/0022-3514.51.6.1173"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a010256"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1214\/ss\/1032280304"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.04.011"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20081885"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.137323.112"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.2307\/2290687"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)00930-2"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00958.x"},{"key":"e_1_2_8_12_1","unstructured":"Centers for Disease Control and Prevention. 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