TY - JOUR
T1 - Potential misinterpretation of the case-only study to assess gene- environment interaction
AU - Schmidt, Silke
AU - Schaid, Daniel J.
N1 - Funding Information:
This research was partially supported by the German Academic Exchange Service (DAAD), Doktoranden-programm HSP EH, and United States National Institutes of Health grant GM51256.
PY - 1999/10/15
Y1 - 1999/10/15
N2 - Novel epidemiologic study designs are often required to assess gene- environment interaction. A design using only cases, without controls, is one of several approaches that have been proposed as more efficient alternatives to the typical random sampling of cases and controls. However, it has not been pointed out that a case-only analysis estimates a different interaction parameter than does a traditional case-control analysis: The latter typically estimates departure from multiplicative population odds or rate ratios, depending on the method of control selection, while the former estimates departure from multiplicative risk ratios if genotype and environmental exposure are not associated in the population. These parameters are approximately equal if the disease risk is small at all levels of the study variables. The authors quantify the impact of allowing for higher disease risk among gene carriers, a relevant situation when the gene under study is highly penetrant. Their findings show that the cross-product ratio computed from case-only data may be substantially smaller than the odds ratio computed from case-control data and may therefore underestimate either the population odds or the rate ratio. Thus, to avoid misinterpretation of interaction parameters estimated from case-only data, the definition of multiplicative interaction should be made explicit.
AB - Novel epidemiologic study designs are often required to assess gene- environment interaction. A design using only cases, without controls, is one of several approaches that have been proposed as more efficient alternatives to the typical random sampling of cases and controls. However, it has not been pointed out that a case-only analysis estimates a different interaction parameter than does a traditional case-control analysis: The latter typically estimates departure from multiplicative population odds or rate ratios, depending on the method of control selection, while the former estimates departure from multiplicative risk ratios if genotype and environmental exposure are not associated in the population. These parameters are approximately equal if the disease risk is small at all levels of the study variables. The authors quantify the impact of allowing for higher disease risk among gene carriers, a relevant situation when the gene under study is highly penetrant. Their findings show that the cross-product ratio computed from case-only data may be substantially smaller than the odds ratio computed from case-control data and may therefore underestimate either the population odds or the rate ratio. Thus, to avoid misinterpretation of interaction parameters estimated from case-only data, the definition of multiplicative interaction should be made explicit.
KW - Case-control studies
KW - Epidemiologic methods
KW - Gene-environment interaction
KW - Interaction
KW - Odds ratio
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U2 - 10.1093/oxfordjournals.aje.a010093
DO - 10.1093/oxfordjournals.aje.a010093
M3 - Article
C2 - 10522659
AN - SCOPUS:0033569885
SN - 0002-9262
VL - 150
SP - 878
EP - 885
JO - American journal of epidemiology
JF - American journal of epidemiology
IS - 8
ER -