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We propose VarGuid, a variance\u2010guided framework for two related settings: Covariate\u2010dependent conditional variance under a global linear mean model, and residual nonlinear mean structure that can mimic heteroscedasticity. The framework has two deliberately separated components. The first uses an iteratively reweighted regression (IRR) algorithm to estimate a sparse global linear mean\u2013variance model and support coefficient interpretation. The second uses a biconvex artificial\u2010grouping algorithm for conditional prediction, keeping the fitted linear backbone fixed while adding group\u2010specific local intercept corrections. We establish predictive\u2010risk guarantees for the global estimator, and simulations and empirical studies show improved out\u2010of\u2010sample accuracy. VarGuid is illustrated in two applications: Health\u2010related quality of life in low\u2010 and middle\u2010income countries, and high\u2010dimensional genomic prediction of lymph node evaluation in breast cancer.<\/jats:p>","DOI":"10.1002\/sim.70632","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T01:26:57Z","timestamp":1780882017000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Variance\u2010Guided Regression for Heteroscedastic Data With a Grouping\u2010Based Extension for Nonlinear Prediction"],"prefix":"10.1002","volume":"45","author":[{"given":"Sibei","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Biostatistics Miller School of Medicine, University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Biostatistics Miller School of Medicine, University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,7]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-9868.2011.00778.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jrsssb\/qkad004"},{"key":"e_1_2_11_4_1","volume-title":"Applied Linear Statistical Models","author":"Neter J.","year":"1996"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/00031305.2000.10474549"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0032553"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.2017.1328360"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1992.tb01903.x"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1989.tb01747.x"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-095X(199911\/12)10:6<695::AID-ENV385>3.0.CO;2-M"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/03610918.2018.1458136"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(24)00233-X"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201306-1060OC"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/15412555.2011.586660"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chpulm.2024.100113"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.2307\/1912526"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-20192-9"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1214\/12-STS400"},{"key":"e_1_2_11_19_1","first-page":"66","volume-title":"Statistical Modelling: Proceedings of the 14th International Workshop on Statistical Modelling, Graz, Austria","author":"Gordon K.","year":"1999"},{"issue":"547","key":"e_1_2_11_20_1","first-page":"1805","article-title":"Classified Mixed Model Projections","volume":"119","author":"Sunil Rao J.","year":"2024","journal-title":"Journal of the American Statistical Association"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/10618600.2014.948181"},{"key":"e_1_2_11_22_1","unstructured":"H.IshwaranandU. 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