Tan Qihua, Zhao Jing Hua, Zhang Dongfeng, Kruse Torben A, Christensen Kaare
Department of Biochemistry, Pharmacology and Genetics, Odense University Hospital, Sdr. Boulevard 29, DK-5000 Odense C, Denmark.
Am J Epidemiol. 2008 Oct 15;168(8):890-6. doi: 10.1093/aje/kwn205. Epub 2008 Aug 27.
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.
在基因与长寿关联研究中，常用的病例对照设计的效率需要得到验证，因为与二元性状不同，长寿仅代表连续寿命分布的极端情况，没有明确的界限来定义表型。在本文中，作者利用丹麦当前的生命表，通过各种情景模拟个体寿命，并评估当病例定义为百岁老人或九旬老人时，不同样本量的实证检验效能。结果表明，虽然使用少量百岁老人样本（几百人）仅能检测出具有大效应的常见等位基因（风险率降低>20%），但大量百岁老人样本（>1000人）则有能力捕捉到产生微小效应的基因（根据遗传模式，风险降低5%-10%）。虽然该方法对具有相乘或显性效应的罕见等位基因具有良好的检验效能，但对罕见隐性等位基因的表现较差。当把九旬老人视为病例时，检验效能会大幅降低，要达到与百岁老人相当的检验效能，所需病例样本量相差超过5倍。
