ArticleBMC medical genetics2009
Genome-wide association reveals three SNPs associated with sporadic amyotrophic lateral sclerosis through a two-locus analysis.
Article in BMC medical genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 33 citations in OpenAlex.
- An in silico protocol for predicting genetic biomarkers in rare diseases: a case study in sporadic amyotrophic lateral sclerosis.Frontiers in genetics · 2026Article
- Novel Alzheimer's disease genes and epistasis identified using machine learning GWAS platform.Scientific reports · 2023Article
- Gene targeting in amyotrophic lateral sclerosis using causality-based feature selection and machine learning.Molecular medicine (Cambridge, Mass.) · 2023Article
- Selecting Genetic Variants and Interactions Associated with Amyotrophic Lateral Sclerosis: A Group LASSO Approach.Journal of personalized medicine · 2022Article
- A comparison of methods for interpreting random forest models of genetic association in the presence of non-additive interactions.BioData mining · 2021Article
- What Can Machine Learning Approaches in Genomics Tell Us about the Molecular Basis of Amyotrophic Lateral Sclerosis?Journal of personalized medicine · 2020Review
- The search for gene-gene interactions in genome-wide association studies: challenges in abundance of methods, practical considerations, and biological interpretation.Annals of translational medicine · 2018Article
- Pathway-guided identification of gene-gene interactions.Annals of human genetics · 2014Article
- An omnibus permutation test on ensembles of two-locus analyses can detect pure epistasis and genetic heterogeneity in genome-wide association studies.SpringerPlus · 2013Article
- The Role of immune and inflammatory mechanisms in ALS.Current molecular medicine · 2011Review
- Using biological knowledge to uncover the mystery in the search for epistasis in genome-wide association studies.Annals of human genetics · 2011Review
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundAmyotrophic lateral sclerosis (ALS) is a fatal, degenerative neuromuscular disease characterized by a progressive loss of voluntary motor activity. About 95% of ALS patients are in "sporadic form"-meaning their disease is not associated with a family history of the disease. To date, the genetic factors of the sporadic form of ALS are poorly understood.
methodsWe proposed a two-stage approach based on seventeen biological plausible models to search for two-locus combinations that have significant joint effects to the disease in a genome-wide association study (GWAS). We used a two-stage strategy to reduce the computational burden associated with performing an exhaustive two-locus search across the genome. In the first stage, all SNPs were screened using a single-marker test. In the second stage, all pairs made from the 1000 SNPs with the lowest p-values from the first stage were evaluated under each of the 17 two-locus models.
resultswe performed the two-stage approach on a GWAS data set of sporadic ALS from the SNP Database at the NINDS Human Genetics Resource Center DNA and Cell Line Repository http://ccr.coriell.org/ninds/. Our two-locus analysis showed that two two-locus combinations--rs4363506 (SNP1) and rs3733242 (SNP2), and rs4363506 and rs16984239 (SNP3) -- were significantly associated with sporadic ALS. After adjusting for multiple tests and multiple models, the combination of SNP1 and SNP2 had a p-value of 0.032 under the Dom intersection Dom epistatic model; SNP1 and SNP3 had a p-value of 0.042 under the Dom x Dom multiplicative model.
conclusionThe proposed two-stage analytical method can be used to search for joint effects of genes in GWAS. The two-stage strategy decreased the computational time and the multiple testing burdens associated with GWAS. We have also observed that the loci identified by our two-stage strategy can not be detected by single-locus tests.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.