{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T12:20:53Z","timestamp":1781439653806,"version":"3.54.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2018,7,6]],"date-time":"2018-07-06T00:00:00Z","timestamp":1530835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 MH101822"],"award-info":[{"award-number":["R01 MH101822"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HL133218"],"award-info":[{"award-number":["R01 HL133218"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U01 HG007900"],"award-info":[{"award-number":["U01 HG007900"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sloan Faculty Fellowship"},{"name":"NSF CAREER","award":["AWD1005627"],"award-info":[{"award-number":["AWD1005627"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 HL133218"],"award-info":[{"award-number":["R01 HL133218"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U01 HG007900"],"award-info":[{"award-number":["U01 HG007900"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NSF CAREER","award":["AWD1005627"],"award-info":[{"award-number":["AWD1005627"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Identifying variants, both discrete and continuous, that are associated with quantitative traits, or QTs, is the primary focus of quantitative genetics. Most current methods are limited to identifying mean effects, or associations between genotype or covariates and the mean value of a quantitative trait. It is possible, however, that a variant may affect the variance of the quantitative trait in lieu of, or in addition to, affecting the trait mean. Here, we develop a general methodology to identify covariates with variance effects on a quantitative trait using a Bayesian heteroskedastic linear regression model (BTH). We compare BTH with existing methods to detect variance effects across a large range of simulations drawn from scenarios common to the analysis of quantitative traits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We find that BTH and a double generalized linear model (dglm) outperform classical tests used for detecting variance effects in recent genomic studies. We show BTH and dglm are less likely to generate spurious discoveries through simulations and application to identifying methylation variance QTs and expression variance QTs. We identify four variance effects of sex in the Cardiovascular and Pharmacogenetics study. Our work is the first to offer a comprehensive view of variance identifying methodology. We identify shortcomings in previously used methodology and provide a more conservative and robust alternative. We extend variance effect analysis to a wide array of covariates that enables a new statistical dimension in the study of sex and age specific quantitative trait effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>https:\/\/github.com\/b2du\/bth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty565","type":"journal-article","created":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T19:39:34Z","timestamp":1530733174000},"page":"200-210","source":"Crossref","is-referenced-by-count":32,"title":["Statistical tests for detecting variance effects in quantitative trait studies"],"prefix":"10.1093","volume":"35","author":[{"given":"Bianca","family":"Dumitrascu","sequence":"first","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Darnell","sequence":"additional","affiliation":[{"name":"Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Ayroles","sequence":"additional","affiliation":[{"name":"Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara E","family":"Engelhardt","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Princeton University, Princeton, NJ, USA"},{"name":"Center for Statistics and Machine Learning, Princeton University, Princeton, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,6]]},"reference":[{"key":"2023013107225034600_bty565-B1","doi-asserted-by":"crossref","first-page":"e1000049.","DOI":"10.1371\/journal.pgen.1000049","article-title":"Cell-to-cell stochastic variation in gene expression is a complex genetic trait","volume":"4","author":"Ansel","year":"2008","journal-title":"PLoS Genet"},{"key":"2023013107225034600_bty565-B3","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1534\/genetics.110.114983","article-title":"Statistical design and analysis of RNA sequencing data","volume":"185","author":"Auer","year":"2010","journal-title":"Genetics"},{"key":"2023013107225034600_bty565-B4","doi-asserted-by":"crossref","first-page":"6706","DOI":"10.1073\/pnas.1503830112","article-title":"Behavioral idiosyncrasy reveals genetic control of phenotypic variability","volume":"112","author":"Ayroles","year":"2015","journal-title":"Proc. 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