{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T04:35:22Z","timestamp":1717389322502},"reference-count":27,"publisher":"BMJ","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Occup Environ Med"],"published-print":{"date-parts":[[2009,6]]},"abstract":"<jats:sec><jats:title>Objectives:<\/jats:title><jats:p>This study seeks to assess the impact of measurement errors in cumulative exposure on estimates of a gene-environment interaction in a nested case-control study in occupational epidemiology. In the approach considered here, exposure intensity is assessed at the group level and the exposure duration individually (both with error). Genetic susceptibility is assumed to be known exactly. Differences in \u201cgene\u201d are assumed to affect disease risk only in exposed subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Three data analysis strategies were considered: one using a correctly specified disease model (exposure and exposure-gene interaction), and two using mis-specified disease models, one with \u201cgene\u201d as the only risk factor (\u201cgene-only\u201d model) and the other with main effects of both gene and exposure along with their interaction (\u201cfull\u201d model).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>In simulations, estimates of the gene-environment interaction based on the correctly specified disease model were greatly attenuated and power was diminished appreciably even when errors in exposure were modest. Significant associations were detected more frequently in the gene-only model when errors in exposure were large. When the \u201cfull\u201d mis-specified model was fitted to the simulated data, it yielded erratic estimates. This is illustrated in an analysis of the interaction of cumulative exposure to organophosphate pesticides and paraoxonase gene on the risk of chronic neuropsychological effects among farmers who dip sheep.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p>If \u201cgene\u201d contributes to disease risk only in the presence of exposure, the existence of the gene-environment interaction can be efficiently inferred from a deliberately mis-specified \u201cgene-only\u201d disease model in nested case-control studies.<\/jats:p><\/jats:sec>","DOI":"10.1136\/oem.2008.039081","type":"journal-article","created":{"date-parts":[[2008,11,19]],"date-time":"2008-11-19T03:29:03Z","timestamp":1227065343000},"page":"374-380","source":"Crossref","is-referenced-by-count":12,"title":["The virtues of a deliberately mis-specified disease model in demonstrating a gene-environment 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