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Article

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

by
Sofia Galvão Feronato
1,
Maria Luiza Matos Silva
2,
Rafael Izbicki
2,
Ticiana D. J. Farias
1,3,
Patrícia Shigunov
1,
Bruno Dallagiovanna
1,
Fabio Passetti
1 and
Hellen Geremias dos Santos
1,*
1
Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81310-020, Brazil
2
Department of Statistics, Universidade Federal de São Carlos, São Carlos 13565-905, Brazil
3
Division of Biomedical Informatics, Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2022, 12(8), 1330; https://doi.org/10.3390/jpm12081330
Submission received: 20 May 2022 / Revised: 10 August 2022 / Accepted: 12 August 2022 / Published: 19 August 2022
(This article belongs to the Special Issue Application of Bioinformatics in Precision Medicine)
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Abstract

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.
Keywords: amyotrophic lateral sclerosis; genome-wide association studies; group LASSO regularization; single-nucleotide polymorphisms; pairwise interaction amyotrophic lateral sclerosis; genome-wide association studies; group LASSO regularization; single-nucleotide polymorphisms; pairwise interaction
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MDPI and ACS Style

Feronato, S.G.; Silva, M.L.M.; Izbicki, R.; Farias, T.D.J.; Shigunov, P.; Dallagiovanna, B.; Passetti, F.; dos Santos, H.G. Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach. J. Pers. Med. 2022, 12, 1330. https://doi.org/10.3390/jpm12081330

AMA Style

Feronato SG, Silva MLM, Izbicki R, Farias TDJ, Shigunov P, Dallagiovanna B, Passetti F, dos Santos HG. Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach. Journal of Personalized Medicine. 2022; 12(8):1330. https://doi.org/10.3390/jpm12081330

Chicago/Turabian Style

Feronato, Sofia Galvão, Maria Luiza Matos Silva, Rafael Izbicki, Ticiana D. J. Farias, Patrícia Shigunov, Bruno Dallagiovanna, Fabio Passetti, and Hellen Geremias dos Santos. 2022. "Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach" Journal of Personalized Medicine 12, no. 8: 1330. https://doi.org/10.3390/jpm12081330

APA Style

Feronato, S. G., Silva, M. L. M., Izbicki, R., Farias, T. D. J., Shigunov, P., Dallagiovanna, B., Passetti, F., & dos Santos, H. G. (2022). Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach. Journal of Personalized Medicine, 12(8), 1330. https://doi.org/10.3390/jpm12081330

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