Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach

• Published in: Journal of personalized medicine Vol. 12; no. 8; p. 1330
• Main Authors: Feronato, Sofia Galvão, Silva, Maria Luiza Matos, Izbicki, Rafael, Farias, Ticiana D. J., Shigunov, Patrícia, Dallagiovanna, Bruno, Passetti, Fabio, dos Santos, Hellen Geremias
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 19-08-2022; MDPI
• Subjects: Amyotrophic lateral sclerosis; Datasets; Feature selection; Genetic diversity; Genomes; Genotype & phenotype; Motor neurons; Nervous system; Neurodegenerative diseases; Precision medicine; Regularization methods; Single-nucleotide polymorphism; Variables
• ISSN: 2075-4426; 2075-4426
• DOI: 10.3390/jpm12081330

Amyotrophic lateral sclerosis (ALS) is a multi-system neurodegenerative disease that affects both upper and lower motor neurons, resulting from a combination of genetic, environmental, and lifestyle factors. Usually, the association between single-nucleotide polymorphisms (SNPs) and this disease is tested individually, which leads to the testing of multiple hypotheses. In addition, this classical approach does not support the detection of interaction-dependent SNPs. We applied a two-step procedure to select SNPs and pairwise interactions associated with ALS. SNP data from 276 ALS patients and 268 controls were analyzed by a two-step group LASSO in 2000 iterations. In the first step, we fitted a group LASSO model to a bootstrap sample and a random subset of predictors (25%) from the original data set aiming to screen for important SNPs and, in the second step, we fitted a hierarchical group LASSO model to evaluate pairwise interactions. An in silico analysis was performed on a set of variables, which were prioritized according to their bootstrap selection frequency. We identified seven SNPs (rs16984239, rs10459680, rs1436918, rs1037666, rs4552942, rs10773543, and rs2241493) and two pairwise interactions (rs16984239:rs2118657 and rs16984239:rs3172469) potentially involved in nervous system conservation and function. These results may contribute to the understanding of ALS pathogenesis, its diagnosis, and therapeutic strategy improvement.