RE: "CHOOSING A RETROSPECTIVE DESIGN TO ASSESS JOINT GENETIC AND ENVIRONMENTAL CONTRIBUTIONS TO RISK"

Devendra Amre and Isabel Fortier

Research Center Saint-Justine Hospital 3175 Côte-Sainte-Catherine Montreal, PQ H3T1C5, Canada


    INTRODUCTION
 TOP
 INTRODUCTION
 REFERENCES
 
In their recent commentary, Weinberg and Umbach (1Go) provided an excellent overview on retrospective designs for assessing the contributions of gene-environment interactions to risk. Contrasts were made between population-based case-control studies, family-based studies (selecting siblings and cousins as controls), case-only studies, and case-parent studies. Although Weinberg and Umbach did not recommend the use of any particular design over another, they inferred that family-based designs may become the design of choice when joint effects of genes and exposures are studied. Certainly this type of design will be appropriate in many circumstances, especially those where controlling for genetic admixture is of primary importance. As was also suggested, population-based case-control studies would be equally informative (among other circumstances) when conducted among genetically homogeneous or genetically heterogeneous populations.

In our opinion, one variant of the case-control study, the hospital-based case-control study, deserves comment. In most practical situations, when a single population source for cases is unavailable or cannot be identified (which is true more often than not), researchers usually recruit cases from one or more hospitals serving a defined geographic area. When they do so, selecting other diseased subjects from the same hospitals as controls, as opposed to population controls, is the justified choice, especially when not all of the hospitals serving the population have been included (2Go). As Weinberg and Umbach (1Go) pointed out, response rates for genotyping potentially healthy population controls for population-based case-control studies and siblings or cousins for family-based case-control studies are likely to be very low. These low response rates (as low as 30 percent, in our experience) would, in all probability, jeopardize results. On the other hand, in hospital-based designs, other diseased patients are more motivated and are more easily accessible for obtaining genetic material. In addition, selection bias related to referral and access is generally lower. Selecting a random sample of controls covering different diseases would greatly reduce bias resulting from the possibility of any particular control disease's being associated with the genotype and/or exposure (3Go).

In fact, many times these benefits would outweigh the advantages gained from using sibling or cousin controls in family-based studies, where, in addition to low response rates, overmatching on exposure could greatly increase the number of subjects required for the study. This is even more true for studies investigating pediatric outcomes when siblings are likely to have similar exposures (e.g., regarding dietary habits). Overmatching, supplemented with the need to exclude cases without siblings (very often the situation in North America), may substantially undermine the potential benefits of the family-based design. If close matching on race/ethnicity is possible in hospital-based designs, confounding associated with genetic admixture can be substantially reduced.

Given these advantages and for practical reasons related to cost and feasibility, hospital-based case-control studies, despite their potential limitations, are excellent alternatives. In most circumstances they should be considered appropriate for the assessment of joint genetic and environmental contributions to risk.


    NOTES
 
Editor's note: In accordance with Journal policy, Drs. Weinberg and Umbach were asked whether they wished to respond to this letter, but they chose not to do so.


    REFERENCES
 TOP
 INTRODUCTION
 REFERENCES
 

  1. Weinberg CR, Umbach DM. Choosing a retrospective design to assess joint genetic and environmental contributions to risk. Am J Epidemiol 2000;152:197–203.[Abstract/Free Full Text]
  2. Stolley PD, Schlesselman JJ. Planning and conducting a study. In: Schlesselman JJ, ed. Case-control studies: design, conduct, analysis. New York, NY: Oxford University Press, Inc, 1982:69–101.
  3. Wacholder S, Silverman DT, McLaughlin JK, et al. Selection of controls in case-control studies. III. Design options. Am J Epidemiol 1992;135:1042–50.[Abstract]




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