{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:51:49Z","timestamp":1760151109255,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["U01DE017018","R03DE023592"],"award-info":[{"award-number":["U01DE017018","R03DE023592"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["T32ES007018","R01ES021900.","P03ES010126"],"award-info":[{"award-number":["T32ES007018","R01ES021900.","P03ES010126"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["0646083"],"award-info":[{"award-number":["0646083"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P01CA142538"],"award-info":[{"award-number":["P01CA142538"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001111"],"award-info":[{"award-number":["UL1TR001111"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Stats"],"abstract":"<jats:p>Traditional case\u2013control genetic association studies examine relationships between case\u2013control status and one or more covariates. It is becoming increasingly common to study secondary phenotypes and their association with the original covariates. The Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project, a study of temporomandibular disorders (TMD), motivates this work. Numerous measures of interest are collected at enrollment, such as the number of comorbid pain conditions from which a participant suffers. Examining the potential genetic basis of these measures is of secondary interest. Assessing these associations is statistically challenging, as participants do not form a random sample from the population of interest. Standard methods may be biased and lack coverage and power. We propose a general method for the analysis of arbitrary phenotypes utilizing inverse probability weighting and bootstrapping for standard error estimation. The method may be applied to the complicated association tests used in next-generation sequencing studies, such as analyses of haplotypes with ambiguous phase. Simulation studies show that our method performs as well as competing methods when they are applicable and yield promising results for outcome types, such as time-to-event, to which other methods may not apply. The method is applied to the OPPERA baseline case\u2013control genetic study.<\/jats:p>","DOI":"10.3390\/stats5010014","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T22:35:00Z","timestamp":1645569300000},"page":"203-214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modeling Secondary Phenotypes Conditional on Genotypes in Case\u2013Control Studies"],"prefix":"10.3390","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9991-427X","authenticated-orcid":false,"given":"Naomi C.","family":"Brownstein","sequence":"first","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianwen","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7420, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2056-225X","authenticated-orcid":false,"given":"Shad","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luda","family":"Diatchenko","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montr\u00e9al, QC H3A 0G1, Canada"},{"name":"Department of Anesthesia, Faculty of Medicine, McGill University, Montr\u00e9al, QC H3A 0G1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary D.","family":"Slade","sequence":"additional","affiliation":[{"name":"School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7450, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Bair","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7420, USA"},{"name":"School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7450, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1093\/biomet\/66.3.403","article-title":"Logistic Disease Incidence Models and Case-Control Studies","volume":"66","author":"Prentice","year":"1979","journal-title":"Biometrika"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/gepi.20424","article-title":"Genome-wide association scans for secondary traits using case-control samples","volume":"33","author":"Monsees","year":"2009","journal-title":"Genet. 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