arXiv subjects

Fernando Castro-Prado

Publications and source records attributed to Fernando Castro-Prado.

5 recordsLinked to original sources

arXiv2025

A generalized distance covariance framework for genome-wide association studies

When testing for the association of a single SNP with a phenotypic response, one usually considers an additive genetic model, assuming that the mean of of the response for the heterozygous state is the average of the means for the two homozygous states. However, this simplification often does not hold. In this paper, we present a novel framework for testing the association of a single SNP and a phenotype. Different from the predominant standard approach, our methodology is guaranteed to detect all dependencies expressed by classical genetic association models. The asymptotic distribution under mild regularity assumptions is derived. Moreover, the finite sample distribution under Gaussianity is provided in which the exact p-value can be efficiently evaluated via the classical Appell hypergeometric series. Both results are extended to a regression-type setting with nuisance covariates, enabling hypotheses testing in a wide range of scenarios. A connection of our approach to score tests is explored, leading to intuitive interpretations as locally most powerful tests. A simulation study demonstrates the computational efficiency and excellent statistical performance of the proposed methodology. A real data example is provided.

stat.ME↗

arXiv2024

Nonparametric independence tests in high-dimensional settings, with applications to the genetics of complex disease

[PhD thesis of FCP.] Nowadays, genetics studies large amounts of very diverse variables. Mathematical statistics has evolved in parallel to its applications, with much recent interest high-dimensional settings. In the genetics of human common disease, a number of relevant problems can be formulated as tests of independence. We show how defining adequate premetric structures on the support spaces of the genetic data allows for novel approaches to such testing. This yields a solid theoretical framework, which reflects the underlying biology, and allows for computationally-efficient implementations. For each problem, we provide mathematical results, simulations and the application to real data.

stat.ME↗

arXiv2024

Tests for categorical data beyond Pearson: A distance covariance and energy distance approach

Categorical variables are of uttermost importance in biomedical research. When two of them are considered, it is often the case that one wants to test whether or not they are statistically dependent. We show weaknesses of classical methods -- such as Pearson's and the G-test -- and we propose testing strategies based on distances that lack those drawbacks. We first develop this theory for classical two-dimensional contingency tables, within the context of distance covariance, an association measure that characterizes general statistical independence of two variables. We then apply the same fundamental ideas to one-dimensional tables, namely to the testing for goodness of fit to a discrete distribution, for which we resort to an analogous statistic called energy distance. We prove that our methodology has desirable theoretical properties, and we show that we can calibrate the null distribution of our test statistics without resampling. We illustrate all this in simulations, as well as with some real data examples, demonstrating the adequate performance of our approach for biostatistical practice.

stat.ME↗

arXiv2020

Testing for genetic interactions in complex disease with distance correlation

Understanding epistasis (genetic interaction) may shed some light on the genomic basis of common diseases, including disorders of maximum interest due to their high socioeconomic burden, like schizophrenia. Distance correlation is an association measure that characterises general statistical independence between random variables, not only the linear one. Here, we propose distance correlation as a novel tool for the detection of epistasis from case-control data of single-nucleotide polymorphisms (SNPs). On the methodological side, we highlight the derivation of the explicit asymptotic distribution of the test statistic. We show that this is the only way to obtain enough computational speed for the method to be used in practice, in a scenario where the resampling techniques found in the literature are impractical. Our simulations show satisfactory calibration of significance, as well as comparable or better power than existing methodology. We conclude with the application of our technique to a schizophrenia genetics dataset, obtaining biologically sound insights.

math.ST↗

arXiv2020

Nonparametric independence tests in metric spaces: What is known and what is not

Distance correlation is a recent extension of Pearson's correlation, that characterises general statistical independence between Euclidean-space-valued random variables, not only linear relations. This review delves into how and when distance correlation can be extended to metric spaces, combining the information that is available in the literature with some original remarks and proofs, in a way that is comprehensible for any mathematical statistician.

math.ST↗