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Case-control studies are commonly used in clinical research to test the association of risk factors with diseases. Typically, the comparison subjects selected are unrelated to the cases. However, the use of unrelated controls may introduce bias when the studies are conducted in ethnically heterogeneous populations such as the United States.1 Specifically, disease and risk factor frequencies (genetic and environmental) may vary according to ethnicity. Unequal distributions of ethnic subgroups in case and unrelated control samples may therefore result in spurious association findings (population stratification bias).
By contrast, in the absence of nonpaternity, case-unaffected sibling pairs are matched for ethnicity. Therefore, statistical methods have been developed to compare the frequency of risk factors in discordant sibling pairs (e.g., sibling transmission disequilibrium test).2 Although family-based association studies have been employed primarily for the study of genetic factors, the same design can be employed for the study of environmental factors.3
Indeed, in this issue of Neurology, Scott et al.3 report findings from a family-based case-control study of cigarette smoking and Parkinson disease (PD). They interviewed 143 PD cases and their 168 unaffected siblings …
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