{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T15:22:53Z","timestamp":1772810573683,"version":"3.50.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T00:00:00Z","timestamp":1556150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL129132"],"award-info":[{"award-number":["R01HL129132"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK093757"],"award-info":[{"award-number":["R01DK093757"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>Tens of thousands of reproducibly identified GWAS (Genome-Wide Association Studies) variants, with the vast majority falling in non-coding regions resulting in no eventual protein products, call urgently for mechanistic interpretations. Although numerous methods exist, there are few, if any methods, for simultaneously testing the mediation effects of multiple correlated SNPs via some mediator (e.g. the expression of a gene in the neighborhood) on phenotypic outcome. We propose multi-SNP\u00a0mediation intersection-union\u00a0test (SMUT) to fill in this methodological gap. Our extensive simulations demonstrate the validity of SMUT as well as substantial, up to 92%, power gains over alternative methods. In addition, SMUT confirmed known mediators in a real dataset of Finns for plasma adiponectin level, which were missed by many alternative methods. We believe SMUT will become a useful tool to generate mechanistic hypotheses underlying GWAS variants, facilitating functional follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>The R package SMUT is publicly available from CRAN at https:\/\/CRAN.R-project.org\/package=SMUT.<\/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\/btz285","type":"journal-article","created":{"date-parts":[[2019,4,16]],"date-time":"2019-04-16T15:22:31Z","timestamp":1555428151000},"page":"4724-4729","source":"Crossref","is-referenced-by-count":25,"title":["Multi-SNP mediation intersection-union test"],"prefix":"10.1093","volume":"35","author":[{"given":"Wujuan","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Biostatistics, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cassandra N","family":"Spracklen","sequence":"additional","affiliation":[{"name":"Department of Genetics, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L","family":"Mohlke","sequence":"additional","affiliation":[{"name":"Department of Genetics, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599, 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, NC 27599, USA"},{"name":"Department of Statistics and Operations Research, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599, USA"},{"name":"Department of Genetics, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599, USA"},{"name":"Department of Computer Science, The University of North Carolina at Chapel Hill , Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,4,25]]},"reference":[{"key":"2023013108343302400_btz285-B1","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/gepi.22061","article-title":"A comparison of methods for inferring causal relationships between genotype and phenotype using additional biological measurements","volume":"41","author":"Ainsworth","year":"2017","journal-title":"Genet. 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