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

AI Article Synopsis

  • ALS is a neurodegenerative disease affecting motor neurons, influenced by genetic, environmental, and lifestyle factors.
  • Traditional research often tests SNPs individually, missing interactions; this study used a new two-step method to analyze SNPs and their interactions.
  • Seven SNPs and two interactions were identified that may play a role in ALS, potentially improving understanding and treatment of the disease.

Article 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 (, , , , , , and ) and two pairwise interactions ( and ) potentially involved in nervous system conservation and function. These results may contribute to the understanding of ALS pathogenesis, its diagnosis, and therapeutic strategy improvement.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9410070PMC
http://dx.doi.org/10.3390/jpm12081330DOI Listing

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