Case-only approach applied in environmental epidemiology: 2 examples of interaction effect using the US National Health and Nutrition Examination Survey (NHANES) datasets

Abstract

IntroductionBy substituting the general ‘susceptibility factor’ concept for the conventional ‘gene’ concept in the case-only approach for gene-environment interaction, the case-only approach can also be used in environmental epidemiology. Under the independence between the susceptibility factor and environmental exposure, the case-only approach can provide a more precise estimate of an interaction effect.MethodsTwo analysis examples of the case-only approach in environmental epidemiology are provided using the 2015–2016 and 2017–2018 US National Health and Nutritional Examination Survey (NHANES): (i) the negative interaction effect between blood chromium level and glycohemoglobin level on albuminuria and (ii) the positive interaction effect between blood cobalt level and old age on albuminuria. The second part of the methods (theoretical backgrounds) summarized the logic and equations provided in previous studies about the case-only approach.Results(i) When a 1 μg/L difference of both blood chromium level (mcg/L) and a 1% difference in blood glycohemoglobin level coincide, the multiplicative interaction contrast ratio (ICRc/nc) was 0.72 (95% CI 0.35–1.60), with no statistical significance. However, when only the cases were analyzed, the case-only ICR (ICRCO) was 0.59 (95% CI 0.28–0.95), with a statistical significance (a negative interaction effect). (ii) When a 1 μg/L difference of both blood cobalt levels and a 1-year difference in age coincide, the multiplicative interaction contrast ratio (ICRc/nc) was 1.13 (95% CI 0.99–1.37), with no statistical significance. However, when only the cases were analyzed, the case-only ICR (ICRCO) was 1.21 (95% CI 1.06–1.51), with a statistical significance (a positive interaction effect).DiscussionThe discussion suggested the theoretical background and previous literature about the possible protective interaction effect between blood chromium levels and blood glycohemoglobin levels on the incidence of albuminuria and the possible aggravating interaction effect between blood cobalt levels and increasing ages on the incidence of albuminuria. If the independence assumption between a susceptibility factor and environmental exposure in a study with cases and non-cases is kept, the case-only approach can provide a more precise interaction effect estimate than conventional approaches with both cases and non-cases.