Evaluation of gene-based family-based methods to detect novel genes associated with familial late onset Alzheimer disease

AbstractGene-based tests to study the combined effect of rare variants towards a particular phenotype have been widely developed for case-control studies, but their evolution and adaptation for family-based studies, especially for complex incomplete families, has been slower. In this study, we have performed a practical examination of all the latest gene-based methods available for family-based study designs using both simulated and real datasets. We have examined the performance of several collapsing, variance-component and transmission disequilibrium tests across eight different software and twenty-two models utilizing a cohort of 285 families (N=1,235) with late-onset Alzheimer disease (LOAD). After a thorough examination of each of these tests, we propose a methodological approach to identify, with high confidence, genes associated with the studied phenotype with high confidence and we provide recommendations to select the best software and model for family-based gene-based analyses. Additionally, in our dataset, we identified PTK2B, a GWAS candidate gene for sporadic AD, along with six novel genes (CHRD, CLCN2, HDLBP, CPAMD8, NLRP9, MAS1L) as candidates genes for familial LOAD.</jats:p

Regularity dependence of the rate of convergence of the learning curve for Gaussian process regression

This paper deals with the speed of convergence of the learning curve in a Gaussian process regression framework. The learning curve describes the average generalization error of the Gaussian process used for the regression. More specifically, it is defined in this paper as the integral of the mean squared error over the input parameter space with respect to the probability measure of the input parameters. The main result is the proof of a theorem giving the mean squared error in function of the number of observations for a large class of kernels and for any dimension when the number of observations is large. From this result, we can deduce the asymptotic behavior of the generalization error. The presented proof generalizes previous ones that were limited to more specific kernels or to small dimensions (one or two). The result can be used to build an optimal strategy for resources allocation. This strategy is applied successfully to a nuclear safety problem