{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T06:10:06Z","timestamp":1756707006902,"version":"3.44.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["112-2628-B-002-024-MY3"],"award-info":[{"award-number":["112-2628-B-002-024-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Detection of variance quantitative trait loci (vQTL) can facilitate the discovery of gene-environment (GxE) and gene-gene interactions (GxG). Identifying vQTLs before direct GxE and GxG analyses can considerably reduce the number of tests and the multiple-testing penalty.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Despite some methods proposed for vQTL detection, few studies have performed a head-to-head comparison simultaneously concerning false positive rates (FPRs), power, and computational time. This work compares three parametric and two non-parametric vQTL tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Simulation studies show that the deviation regression model (DRM) and Kruskal-Wallis test (KW) are the most recommended parametric and non-parametric tests, respectively. The quantile integral linear model (QUAIL, non-parametric) appropriately preserves the FPR under normally or non-normally distributed traits. However, its power is never among the optimal choices, and its computational time is much longer than that of competitors. The Brown-Forsythe test (BF, parametric) can suffer from severe inflation in FPR when SNP\u2019s minor allele frequencies &amp;lt;0.2. The double generalized linear model (DGLM, parametric) is not valid for non-normally distributed traits, although it is the most powerful method for normally distributed traits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Considering the robustness (to outliers) and computation time, I chose KW to analyze four lipid traits in the Taiwan Biobank. I further showed that GxE and GxG were enriched among 30 vQTLs identified from the four lipid traits.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1617504","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T05:30:26Z","timestamp":1756704626000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mining for gene-environment and gene-gene interactions: parametric and non-parametric tests for detecting variance quantitative trait loci"],"prefix":"10.3389","volume":"16","author":[{"given":"Wan-Yu","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e3000870","DOI":"10.1371\/journal.pbio.3000870","article-title":"High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: evidence from two large population cohort studies","volume":"18","author":"Beyene","year":"2020","journal-title":"PLoS Biol. 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