Haldar Tanushree, Ghosh Saurabh
Human Genetics Unit, Indian Statistical Institute, Kolkata, West Bengal, India.
Indian J Hum Genet. 2011 May;17 Suppl 1(Suppl 1):S27-31. doi: 10.4103/0971-6866.80355.
THERE ARE TWO MAJOR CLASSES OF GENETIC ASSOCIATION ANALYSES: population based and family based. Population-based case-control studies have been the method of choice due to the ease of data collection. However, population stratification is one of the major limitations of case-control studies, while family-based studies are protected against stratification. In this study, we carry out extensive simulations under different disease models (both Mendelian as well as complex) to evaluate the relative powers of the two approaches in detecting association.
The power comparisons are based on a case-control design comprising 200 cases and 200 controls versus a Transmission Disequilibrium Test (TDT) or Pedigree Disequilibrium Test (PDT) design with 200 informative trios. We perform the allele-level test for case-control studies, which is based on the difference of allele frequencies at a single nucleotide polymorphism (SNP) between unrelated cases and controls. The TDT and the PDT are based on preferential allelic transmissions at a SNP from heterozygous parents to the affected offspring. We considered five disease modes of inheritance: (i) recessive with complete penetrance (ii) dominant with complete penetrance and (iii), (iv) and (v) complex diseases with varying levels of penetrances and phenocopies.
We find that while the TDT/PDT design with 200 informative trios is in general more powerful than a case-control design with 200 cases and 200 controls (except when the heterozygosity at the marker locus is high), it may be necessary to sample a very large number of trios to obtain the requisite number of informative families.
The current study provides insights into power comparisons between population-based and family-based association studies.
基因关联分析主要有两大类：基于人群的和基于家系的。基于人群的病例对照研究因其数据收集简便而成为首选方法。然而，人群分层是病例对照研究的主要局限之一，而基于家系的研究则可避免分层问题。在本研究中，我们在不同疾病模型（孟德尔模型和复杂模型）下进行了广泛模拟，以评估这两种方法在检测关联方面的相对效能。
效能比较基于一种病例对照设计（包含200例病例和200例对照）与一种传递不平衡检验（TDT）或系谱不平衡检验（PDT）设计（有200个提供信息的三联体）。我们对病例对照研究进行等位基因水平检验，该检验基于无关病例与对照之间单个核苷酸多态性（SNP）处的等位基因频率差异。TDT和PDT基于SNP处从杂合亲本到患病后代的优先等位基因传递。我们考虑了五种疾病遗传模式：（i）完全显性的隐性模式（ii）完全显性的显性模式以及（iii）、（iv）和（v）具有不同显性水平和拟表型的复杂疾病模式。
我们发现，虽然有200个提供信息的三联体的TDT/PDT设计总体上比有200例病例和200例对照的病例对照设计效能更高（标记位点杂合度高时除外），但可能需要对大量三联体进行采样以获得所需数量的提供信息的家系。
本研究为基于人群和基于家系的关联研究之间的效能比较提供了见解。
