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- Title
Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias.
- Authors
Wacholder, Sholom; Rothman, Nathaniel; Wacholder, S; Rothman, N; Caporaso, N
- Abstract
<bold>Background: </bold>Some critics argue that bias from population stratification (the mixture of individuals from heterogeneous genetic backgrounds) undermines the credibility of epidemiologic studies designed to estimate the association between a genotype and the risk of disease. We investigated the degree of bias likely from population stratification in U.S. studies of cancer among non-Hispanic Caucasians of European origin.<bold>Methods: </bold>An expression of the confounding risk ratio-the ratio of the effect of the genetic factor on risk of disease with and without adjustment for ethnicity-is used to measure the potential relative bias from population stratification. We first use empirical data on the frequency of the N-acetyltransferase (NAT2) slow acetylation genotype and incidence rates of male bladder cancer and female breast cancer in non-Hispanic U.S. Caucasians with ancestries from eight European countries to assess the bias in a hypothetical population-based U.S. study that does not take ethnicity into consideration. Then, we provide theoretical calculations of the bias over a large range of allele frequencies and disease rates.<bold>Results: </bold>Ignoring ethnicity leads to a bias of 1% or less in our empirical studies of NAT2. Furthermore, evaluation of a wide range of allele frequencies and representative ranges of cancer rates that exist across European populations shows that the risk ratio is biased by less than 10% in U.S. studies except under extreme conditions. We note that the bias decreases as the number of ethnic strata increases.<bold>Conclusions: </bold>There will be only a small bias from population stratification in a well-designed case-control study of genetic factors that ignores ethnicity among non-Hispanic U.S. Caucasians of European origin. Further work is needed to estimate the effect of population stratification within other populations.
- Subjects
UNITED States; CANCER genetics; CAUCASIAN race; DISEASES
- Publication
JNCI: Journal of the National Cancer Institute, 2000, Vol 92, Issue 14, p1151
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/92.14.1151