ArticlePloS one2011
Practical and theoretical considerations in study design for detecting gene-gene interactions using MDR and GMDR approaches.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Association and Gene-Gene Interactions Study of Late-Onset Alzheimer's Disease in the Russian Population.Genes · 2021Article
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- Candidate Genes for Age at Menarche Are Associated With Uterine Leiomyoma.Frontiers in genetics · 2020Article
- Epistasis of polymorphisms related to the articular cartilage extracellular matrix in knee osteoarthritis: Analysis-based multifactor dimensionality reduction.Genetics and molecular biology · 2020Article
- Impact of the gene-gene interactions related to the HIF-1α signaling pathway with the knee osteoarthritis development.Clinical rheumatology · 2019Article
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- Overview of genomics and post-genomics research on type 2 diabetes mellitus: Future perspectives and a framework for further studies.Journal of biosciences · 2019Review
- Epistatic Interaction Between 5-HT1A and Vascular Endothelial Growth Factor Gene Polymorphisms in the Northern Chinese Han Population With Major Depressive Disorder.Frontiers in psychiatry · 2019Article
- Association of single nucleotide polymorphisms inBioscience reports · 2018Article
- Interaction between polymorphisms in cell-cycle genes and environmental factors in regulating cholinesterase activity in people with exposure to omethoate.Royal Society open science · 2018Article
- Association of Maternal and Fetal Single-Nucleotide Polymorphisms in Metalloproteinase (Disease markers · 2018Article
- Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium.British journal of cancer · 2017Article
- Gene set based association analyses for the WSSV resistance of Pacific white shrimp Litopenaeus vannamei.Scientific reports · 2017Article
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6 authors.
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Abstract
Detection of interacting risk factors for complex traits is challenging. The choice of an appropriate method, sample size, and allocation of cases and controls are serious concerns. To provide empirical guidelines for planning such studies and data analyses, we investigated the performance of the multifactor dimensionality reduction (MDR) and generalized MDR (GMDR) methods under various experimental scenarios. We developed the mathematical expectation of accuracy and used it as an indicator parameter to perform a gene-gene interaction study. We then examined the statistical power of GMDR and MDR within the plausible range of accuracy (0.50∼0.65) reported in the literature. The GMDR with covariate adjustment had a power of >80% in a case-control design with a sample size of ≥2000, with theoretical accuracy ranging from 0.56 to 0.62. However, when the accuracy was <0.56, a sample size of ≥4000 was required to have sufficient power. In our simulations, the GMDR outperformed the MDR under all models with accuracy ranging from 0.56∼0.62 for a sample size of 1000-2000. However, the two methods performed similarly when the accuracy was outside this range or the sample was significantly larger. We conclude that with adjustment of a covariate, GMDR performs better than MDR and a sample size of 1000∼2000 is reasonably large for detecting gene-gene interactions in the range of effect size reported by the current literature; whereas larger sample size is required for more subtle interactions with accuracy <0.56.
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