A Simple Approximation to Bias in Gene-Environment Interaction Estimates When a Case Might Not Be the Case

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dc.contributor.authorLobach, Irynaen
dc.contributor.authorKim, Inyoungen
dc.contributor.authorAlekseyenko, Alexanderen
dc.contributor.authorLobach, Siarheien
dc.contributor.authorZhang, Lien
dc.contributor.departmentStatisticsen
dc.date.accessioned2019-10-24T19:02:07Zen
dc.date.available2019-10-24T19:02:07Zen
dc.date.issued2019-10-09en
dc.description.abstractCase-control genetic association studies are often used to examine the role of the genetic basis in complex diseases, such as cancer and neurodegenerative diseases. The role of the genetic basis might vary by nongenetic (environmental) measures, what is traditionally defined as gene-environment interactions (GxE). A commonly overlooked complication is that the set of clinically diagnosed cases might be contaminated by a subset with a nuisance pathologic state that presents with the same symptoms as the pathologic state of interest. The genetic basis of the pathologic state of interest might differ from that of the nuisance pathologic state. Often, frequencies of the pathologically defined states within the clinically diagnosed set of cases vary by the environment. We derive a simple and general approximation to bias in GxE parameter estimates when the presence of the nuisance pathologic state is ignored. We then perform extensive simulation studies to show that ignoring the presence of the nuisance pathologic state can result in substantial bias in GxE estimates and that the approximation we derived is reasonably accurate in finite samples. We demonstrate the applicability of the proposed approximation in a study of Alzheimer's disease.en
dc.description.notesIL is supported by grant #5R21AG043710-02 from the National Institutes of Health.en
dc.description.sponsorshipNational Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [5R21AG043710-02]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fgene.2019.00886en
dc.identifier.eissn1664-8021en
dc.identifier.other886en
dc.identifier.urihttp://hdl.handle.net/10919/95043en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectAlzheimer's diseaseen
dc.subjectdisease misclassificationen
dc.subjectbiasen
dc.subjectapproximationen
dc.subjectadaptive immune systemen
dc.titleA Simple Approximation to Bias in Gene-Environment Interaction Estimates When a Case Might Not Be the Caseen
dc.title.serialFrontiers in Geneticsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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