Search

Single-nucleotide polymorphisms (SNPs), believed to determine human differences, are widely used to predict risk of diseases. Typically, clinical samples are limited and/or the sampling cost is high. Thus, it is essential to determine an adequate sample size needed to build a classifier based on SNPs. Such a classifier would facilitate correct classifications, while keeping the sample size to a minimum, thereby making the studies cost-effective. For coded SNP data from 2 classes, an optimal classifier and an approximation to its probability of correct classification (PCC) are derived. A linear classifier is constructed and an approximation to its PCC is also derived. These approximations are validated through a variety of Monte Carlo simulations. A sample size determination algorithm based on the criterion, which ensures that the difference between the 2 approximate PCCs is below a threshold, is given and its effectiveness is illustrated via simulations. For the HapMap data on Chinese and Japanese populations, a linear classifier is built using 51 independent SNPs, and the required total sample sizes are determined using our algorithm, as the threshold varies. For example, when the threshold value is 0.05, our algorithm determines a total sample size of 166 (83 for Chinese and 83 for Japanese) that satisfies the criterion.

In this article, we propose a new generalized index to recover relationships between two sets of random vectors by finding the vector projections that minimize an L(2) distance between each projected vector and an unknown function of the other. The unknown functions are estimated using the Nadaraya-Watson smoother. Extensions to multiple sets and groups of multiple sets are also discussed, and a bootstrap procedure is developed to detect the number of significant relationships. All the proposed methods are assessed through extensive simulations and real data analyses. In particular, for environmental data from Los Angeles County, we apply our multiple-set methodology to study relationships between mortality, weather, and pollutants vectors. Here, we detect existence of both linear and nonlinear relationships between the dimension-reduced vectors, which are then used to build nonlinear time-series regression models for the dimension-reduced mortality vector. These findings also illustrate potential use of our method in many other applications. A comprehensive assessment of our methodologies along with their theoretical properties are given in a Web Appendix., (© 2010, The International Biometric Society.)