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American Journal of Epidemiology Advance Access originally published online on August 27, 2008
American Journal of Epidemiology 2008 168(8):890-896; doi:10.1093/aje/kwn205
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American Journal of Epidemiology © The Author 2008. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

PRACTICE OF EPIDEMIOLOGY

Power for Genetic Association Study of Human Longevity Using the Case-Control Design

Qihua Tan, Jing Hua Zhao, Dongfeng Zhang, Torben A. Kruse and Kaare Christensen

Correspondence to Dr. Qihua Tan, Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark (e-mail: qtan{at}health.sdu.dk).

Received for publication April 24, 2008. Accepted for publication June 12, 2008.

The efficiency of the popular case-control design in gene-longevity association studies needs to be verified because, different from a binary trait, longevity represents only the extreme end of the continuous life span distribution without a clear cutoff for defining the phenotype. In this paper, the authors use the current Danish life tables to simulate individual life span by using a variety of scenarios and assess the empirical power for different sample sizes when cases are defined as centenarians or as nonagenarians. Results show that, although using small samples of centenarians (several hundred) provides power to detect only common alleles with large effects (a >20% reduction in hazard rate), large samples of centenarians (>1,000) achieve power to capture genes responsible for minor effects (5%–10% hazard reduction depending on the mode of inheritance). Although the method provides good power for rare alleles with multiplicative or dominant effects, it performs poorly for rare recessive alleles. Power is drastically reduced when nonagenarians are considered cases, with a more than 5-fold difference in the size of the case sample required to achieve comparable power as that found with centenarians.

association; case-control studies; computer simulation; genetics; longevity


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