Recent genome-wide association studies (GWAS) have uncovered the genetic basis of complex traits, but show an under-representation of non-European descent individuals, underscoring a critical gap in genetic research. Here, we assess whether we can improve disease prediction across diverse ancestries using multiomic data. We evaluate the performance of Group-LASSO INTERaction-NET (glinternet) and pretrained lasso in disease prediction focusing on diverse ancestries in the UK Biobank. Models were trained on data from White British and other ancestries and validated across a cohort of over 96,000 individuals for 8 diseases. Out of 96 models trained, we report 16 with statistically significant incremental predictive performance in terms of ROC-AUC scores (p-value < 0.05), found for diabetes, arthritis, gall stones, cystitis, asthma and osteoarthritis. For the interaction and pretrained models that outperformed the baseline, the PRS score was the primary driver behind prediction. Our findings indicate that both interaction terms and pre-training can enhance prediction accuracy but for a limited set of diseases and moderate improvements in accuracy.

Logistic Regression (LR) is a widely used statistical method in empirical binary classification studies. However, real-life scenarios oftentimes share complexities that prevent from the use of the as-is LR model, and instead highlight the need to include high-order interactions to capture data variability. This becomes even more challenging because of: (i) datasets growing wider, with more and more variables; (ii) studies being typically conducted in strongly imbalanced settings; (iii) samples going from very large to extremely small; (iv) the need of providing both predictive models and interpretable results. In this paper we present a novel algorithm, Learning high-order Interactions via targeted Pattern Search (LIPS), to select interaction terms of varying order to include in a LR model for an imbalanced binary classification task when input data are categorical. LIPS's rationale stems from the duality between item sets and categorical interactions. The algorithm relies on an interaction learning step based on a well-known frequent item set mining algorithm, and a novel dissimilarity-based interaction selection step that allows the user to specify the number of interactions to be included in the LR model. In addition, we particularize two variants (Scores LIPS and Clusters LIPS), that can address even more specific needs. Through a set of experiments we validate our algorithm and prove its wide applicability to real-life research scenarios, showing that it outperforms a benchmark state-of-the-art algorithm.

We consider the task of fitting a regression model involving interactions among a potentially large set of covariates, in which we wish to enforce strong heredity. We propose FAMILY, a very general framework for this task. Our proposal is a generalization of several existing methods, such as VANISH [Radchenko and James, 2010], hierNet [Bien et al., 2013], the all-pairs lasso, and the lasso using only main effects. It can be formulated as the solution to a convex optimization problem, which we solve using an efficient alternating directions method of multipliers (ADMM) algorithm. This algorithm has guaranteed convergence to the global optimum, can be easily specialized to any convex penalty function of interest, and allows for a straightforward extension to the setting of generalized linear models. We derive an unbiased estimator of the degrees of freedom of FAMILY, and explore its performance in a simulation study and on an HIV sequence data set.