IJE Advance Access originally published online on April 15, 2005
International Journal of Epidemiology 2005 34(3):711; doi:10.1093/ije/dyi086
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Published by Oxford University Press on behalf of the International Epidemiological Association
Letters to the Editor |
Case recruitment in genetic association studies: larger sample size or greater homogeneity?
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, No. 1, Jen-Ai Road, 1st Section, Taipei, Taiwan. E-mail: wenchung{at}ha.mc.ntu.edu.tw
Sirs—To study the genetic components of complex human diseases, researchers nowadays are relying heavily on the case–control association designs. However, they are often in a dilemma as to whether they should recruit as many affected cases as they can in a study (even though the affected cases recruited in this way may constitute a heterogeneous group), or whether they should instead insist on a stricter case definition to achieve greater homogeneity (even though this may result in a much smaller sample size).
For example, suppose that a researcher intends to map the susceptibility gene(s) of cardiovascular diseases. Should he/she recruit both the patients with myocardial infarction and the patients with stroke as the case group in the study in order to increase the sample size? Or for the sake of homogeneity, should he/she recruit the patients with myocardial infarction (or stroke) only? As a second example, suppose that another researcher wishes to locate the susceptibility gene(s) of prostate cancer. He/she knows that the genetic contributions are larger in the earlier-onset prostate cancer cases than in the later-onset ones. However, the earlier-onset cases are limited in number. How should this researcher choose between greater homogeneity (only the early-onset cases are recruited) and larger sample size (both the early-onset and the late-onset cases are recruited)?
We propose a simple rule to help resolve the aforementioned dilemma. Assume that there are two types of affected cases. The allele frequency for the first (second) type of cases is denoted as p1(p2), and the number of subjects, denoted as n1(n2). We have a control group with allele frequency, p0, and the number of subjects, n0. Without loss of generality, we assume that the first type of affected cases is more genetically determined than the second, i.e. |p1 – p0| > |p2 – p0|. The proposed decision rule is that if
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In the previous example of cardiovascular diseases, suppose that the researcher has at his/her disposal, 300 patients with myocardial infarction (n1 = 300), 300 patients with stroke (n2 = 300), and 600 control subjects (n0 = 600). A literature search revealed that the allele frequencies are p1 = 0.158, p2 = 0.149, and p0 = 0.095, respectively.1 Since
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55 (n1 = 20), and the remaining 80, at age >55 (n2 = 80). He/she also has 100 control subjects (n0 = 100) at his/her disposal. The a priori allele frequencies are p1 = 0.430, p2 = 0.090, and p0 = 0.017, respectively.2–4 Since
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References |
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 Top References |
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1 Helgadottir A, Manolescu A, Thorleifsson G et al. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nature Genet 2004;36:233–39.[CrossRef][ISI][Medline]
2 Carter BS, Beaty TH, Steinberg GD, Childs B, Walsh PC. Mendelian inheritance of familial prostate cancer. Proc Natl Acad Sci USA 1992;89:3367–71.
3 Grönberg H, Damber L, Damber JE, Iselius L. Segregation analysis of prostate cancer in Sweden: support for dominant inheritance. Am J Epidemiol 1997;146:552–57.
4 Schaid DJ, McDonnell SK, Blute ML, Thibodeau SN. Evidence for autosomal dominant inheritance of prostate cancer. Am J Hum Genet 1998;62:1425–38.[CrossRef][ISI][Medline]
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