A structured approach to hypotheses involving continuous exposures over the life course

Smith, Andrew D.A.C.; Joinson, Carol J.; Lawlor, Debbie A.; Smith, Andrew D. A. C.; Joinson, Carol J; Hardy, Rebecca; Lawlor, Debbie A; Heron, Jon; Macdonald-Wallis, Corrie; Tilling, Kate

Abstract

© The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association. Background: Epidemiologists are often interested in examining different hypotheses for how exposures measured repeatedly over the life course relate to later-life outcomes. A structured approach for selecting the hypotheses most supported by theory and observed data has been developed for binary exposures. The aim of this paper is to extend this to include continuous exposures and allow for confounding and missing data. Methods: We studied two examples, the association between: (i) maternal weight during pregnancy and birthweight; and (ii) stressful family events throughout childhood and depression in adolescence. In each example we considered several plausible hypotheses including accumulation, critical periods, sensitive periods, change and effect modification. We used least angle regression to select the hypothesis that explained the most variation in the outcome, demonstrating appropriate methods for adjusting for confounders and dealing with missing data. Results: The structured approach identified a combination of sensitive periods: pre-pregnancy weight, and gestational weight gain 0-20 weeks and 20-40 weeks, as the best explanation for variation in birthweight after adjusting for maternal height. A sensitive period hypothesis best explained variation in adolescent depression, with the association strengthening with the proximity of stressful family events. For each example, these models have theoretical support at least as strong as any competing hypothesis. Conclusions: We have extended the structured approach to incorporate continuous exposures, confounding and missing data. This approach can be used in either an exploratory or a confirmatory setting. The interpretation, plausibility and consistency with causal assumptions should all be considered when proposing and choosing life course hypotheses.

• Journal Article Type: Article
• Acceptance Date: Apr 25, 2016
• Publication Date: Jan 1, 2016
• Deposit Date: Apr 28, 2016
• Publicly Available Date: Jul 6, 2016
• Journal: International Journal of Epidemiology
• Print ISSN: 0300-5771
• Electronic ISSN: 1464-3685
• Publisher: Oxford University Press (OUP)
• Peer Reviewed: Peer Reviewed
• Volume: 45
• Issue: 4
• Pages: 1271-1279
• DOI: https://doi.org/10.1093/ije/dyw164
• Keywords: lifecourse, structured approach, least angle regression (LARS), ALSPAC
• Public URL: https://uwe-repository.worktribe.com/output/910328
• Publisher URL: http://dx.doi.org/10.1093/ije/dyw164
• Contract Date: Apr 28, 2016