arXiv subjects

Lajmi Lakhal-Chaieb

Publications and source records attributed to Lajmi Lakhal-Chaieb.

4 recordsLinked to original sources

arXiv2026

Risk prediction models for breast cancer integrating family history of breast cancer and prophylactic interventions

Breast cancer risk assessment and prediction models are very important tools for the clinical management of healthy women carrying pathogenic variants in known cancer genes. We propose in this paper a comprehensive prediction model for the personalized clinical management of women with pathogenic variants in {\it BRCA1}. This model is able to estimate the risk of BC accounting for the full history of this cancer within the family, the personal and family history of risk-reducing salpingo-oophorectomy as well as the exact age of this intervention among family members. The effect of oophorectomy on the risk of developing breast cancer is evaluated by estimating and conducting inference about the regression coefficients in a Cox model with time-varying covariates. We model the within-family dependence in the ages at onset of cancer using a Gaussian copula whose correlation matrix accommodates the different pairwise family relationships. We develop an iterative algorithm to estimate the parameters of the considered model in the presence of a selection bias. We evaluated the performance of the proposed cancer risk estimation method from family data by simulations and illustrated its use through an application to the breast cancer family registry.

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arXiv2026

Global testing of SNP-methylation interactions on binary phenotypes via a logistic functional regression model

Understanding how genetic and epigenetic factors jointly influence binary health outcomes remains a major challenge in biomedical research. We propose a global test for the overall effect of interactions between DNA methylation and a set of single nucleotide polymorphisms (SNPs) on a binary phenotype. We propose a logistic functional regression model in which methylation measurements at CpG sites are transformed into smooth functional predictors interacting with discrete SNP genotypes through a localized kernel. This framework enables stable inference on region-level interactions while accounting for the spatial structure of methylation around SNPs. Extensive simulations show that the proposed test provides well-calibrated type I error and improved power over classical SNP-CpG pairwise analyses. The practical relevance of the method is illustrated using publicly available methylation and genotyping data from an obesity case-control study.

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arXiv2025

A Functional Approach to Testing Overall Effect of Interaction Between DNA Methylation and SNPs

We introduce a test for the overall effect of interaction between DNA methylation and a set of single nucleotide polymorphisms (SNPs) on a quantitative phenotype. The developed inference procedure is based on a functional approach that extends existing regression models in functional data analysis. Through extensive simulations, we show that the proposed test effectively controls type I error rates and highlights increased empirical power over existing methods, particularly when multiple interactions are present. The use of the proposed test is illustrated with an application to data from obesity patients and controls.

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arXiv2021

Detecting differentially methylated regions in bisulfite sequencing data using quasi-binomial mixed models with smooth covariate effect estimates

Identifying disease-associated changes in DNA methylation can help to gain a better understanding of disease etiology. Bisulfite sequencing technology allows the generation of methylation profiles at single base of DNA. We previously developed a method for estimating smooth covariate effects and identifying differentially methylated regions (DMRs) from bisulfite sequencing data, which copes with experimental errors and variable read depths; this method utilizes the binomial distribution to characterize the variability in the methylated counts. However, bisulfite sequencing data frequently include low-count integers and can exhibit over or under dispersion relative to the binomial distribution. We present a substantial improvement to our previous work by proposing a quasi-likelihood-based regional testing approach which accounts for multiplicative and additive sources of dispersion. We demonstrate the theoretical properties of the resulting tests, as well as their marginal and conditional interpretations. Simulations show that the proposed method provides correct inference for smooth covariate effects and captures the major methylation patterns with excellent power.

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