scholarly journals Generalized multifactor dimensionality reduction approaches to identification of genetic interactions underlying ordinal traits

2018 ◽  
Vol 43 (1) ◽  
pp. 24-36 ◽  
Author(s):  
Ting-Ting Hou ◽  
Feng Lin ◽  
Shasha Bai ◽  
Mario A. Cleves ◽  
Hai-Ming Xu ◽  
...  
Keyword(s):  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Genetic Interactions ◽  
Ordinal Traits

scholarly journals A new efficient method to detect genetic interactions for lung cancer GWAS

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Jennifer Luyapan ◽  
Xuemei Ji ◽  
Siting Li ◽  
Xiangjun Xiao ◽  
Dakai Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Disease Onset ◽  
Genetic Interactions ◽  
Survival Outcomes ◽  
Type I ◽  
Genome Wide Association Studies ◽  
Data Set ◽  
Genome Wide

Abstract Background Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset. Methods To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data. Results Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR 1.24, P = 3.15 × 10–15), as the top marker to predict age of lung cancer onset. Conclusions From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes.

scholarly journals A New Efficient Method to Detect Genetic Interactions for Lung Cancer GWAS

2019 ◽  
Author(s):  
Jennifer Luyapan ◽  
Xuemei Ji ◽  
Xiangjun Xiao ◽  
Dakai Zhu ◽  
Eric J. Duell ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Disease Onset ◽  
Genetic Interactions ◽  
Survival Outcomes ◽  
Type I ◽  
Genome Wide Association Studies ◽  
Data Set ◽  
Genome Wide

Abstract Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We address the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which uses Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset. To demonstrate efficacy, we evaluated this method on two simulation sets to estimate the type I error and power. Simulations show that ES-MDR identifies interactions using less computational workload and allows for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data. Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR = 1.24, P = 3.15 x 10-15), as the top marker to predict age of lung cancer onset. From the results of our extensive simulations and analysis of a large GWAS study, we demonstrate that our method is an efficient algorithm that identifies genetic interactions to include in our models to predict survival outcomes.

scholarly journals A New Efficient Method to Detect Genetic Interactions for Lung Cancer GWAS

2020 ◽  
Author(s):  
Jennifer Luyapan ◽  
Xuemei Ji ◽  
Siting Li ◽  
Xiangjun Xiao ◽  
Dakai Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Disease Onset ◽  
Genetic Interactions ◽  
Survival Outcomes ◽  
Type I ◽  
Genome Wide Association Studies ◽  
Data Set ◽  
Genome Wide

Abstract Background: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset. Methods: To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data. Results: Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR = 1.24, P = 3.15 x 10 -15 ), as the top marker to predict age of lung cancer onset. Conclusions: From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes.

scholarly journals A New Efficient Method to Detect Genetic Interactions for Lung Cancer GWAS

2020 ◽  
Author(s):  
Jennifer Luyapan ◽  
Xuemei Ji ◽  
Siting Li ◽  
Xiangjun Xiao ◽  
Dakai Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Disease Onset ◽  
Genetic Interactions ◽  
Survival Outcomes ◽  
Type I ◽  
Genome Wide Association Studies ◽  
Data Set ◽  
Genome Wide

Abstract Background: Genome-wide association studies (GWAS) have proven successful in predicting genetic risk of disease using single-locus models; however, identifying single nucleotide polymorphism (SNP) interactions at the genome-wide scale is limited due to computational and statistical challenges. We addressed the computational burden encountered when detecting SNP interactions for survival analysis, such as age of disease-onset. To confront this problem, we developed a novel algorithm, called the Efficient Survival Multifactor Dimensionality Reduction (ES-MDR) method, which used Martingale Residuals as the outcome parameter to estimate survival outcomes, and implemented the Quantitative Multifactor Dimensionality Reduction method to identify significant interactions associated with age of disease-onset.Methods: To demonstrate efficacy, we evaluated this method on two simulation data sets to estimate the type I error rate and power. Simulations showed that ES-MDR identified interactions using less computational workload and allowed for adjustment of covariates. We applied ES-MDR on the OncoArray-TRICL Consortium data with 14,935 cases and 12,787 controls for lung cancer (SNPs = 108,254) to search over all two-way interactions to identify genetic interactions associated with lung cancer age-of-onset. We tested the best model in an independent data set from the OncoArray-TRICL data.Results: Our experiment on the OncoArray-TRICL data identified many one-way and two-way models with a single-base deletion in the noncoding region of BRCA1 (HR = 1.24, P = 3.15 x 10-15), as the top marker to predict age of lung cancer onset.Conclusions: From the results of our extensive simulations and analysis of a large GWAS study, we demonstrated that our method is an efficient algorithm that identified genetic interactions to include in our models to predict survival outcomes.

СONTRIBUTION OF POLYMORPHIC VARIATION OF ТP53 AND XRCC1 GENES TO THE SUSCEPTIBILITY TO BREAST CANCER FOR WOMEN OF KYRGYZ AND BELARUSIAN NATIONALITY - A COMPARATIVE STUDY ON MULTIFACTOR DIMENSIONALITY REDUCTION METHODS

2018 ◽  
Vol 64 (1) ◽  
pp. 95-101
Author(s):  
Nazira Aldasheva ◽  
Vyacheslav Kipen ◽  
Zhaynagul Isakova ◽  
Sergey Melnov ◽  
Raisa Smolyakova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Rflp Analysis ◽  
Kyrgyz Republic ◽  
Increased Risk ◽  
Polymorphic Variants ◽  
The Republic

Basing on Multifactor Dimensionality Reduction method we showed that polymorphic variants p.Q399R (rs25487, XRCC1) and p.P72R (rs1042522, TP53) correlated with increased risk of breast cancer for women from the Kyrgyz Republic and the Republic of Belarus. Cohort for investigation included patients with clinically verified breast cancer: 117 women from the Kyrgyz Republic (nationality - Kyrgyz) and 169 - of the Republic of Belarus (nationality - Belarusians). Group for comparison included (healthy patients without history of cancer pathology at the time of blood sampling) 102 patients from the Kyrgyz Republic, 185 - from the Republic of Belarus. Respectively genotyping of polymorphic variants p.Q399R (rs25487, XRCC1) and p.P72R (rs1042522, TP53) was done by PCR-RFLP. Analysis of the intergenic interactions conducted with MDR 3.0.2 software. Both ethnic groups showed an increase of breast cancer risk in the presence of alleles for SNPs Gln p.Q399R (XRCC1) in the heterozygous state: for the group “Kyrgyz” - OR=2,78 (95% CI=[1,60-4,82]), p=0,001; for the group “Belarusians” - OR=1,85 (95% СІ=[1Д1-2,82], p=0,004. Carriers with combination of alleles Gln (p.Q399R, XRCC1) and Pro (p.P72R, TP53) showed statistically significance increases of breast cancer risk as for patients from the Kyrgyz Republic (OR=2,89, 95% CI=[1,33-6,31]), so as for patients from the Republic of Belarus (OR=3,01, 95% CI=[0,79-11,56]).

Multifactor-dimensionality reduction reveals interaction of important gene variants involved in allergy

2015 ◽  
Vol 42 (3) ◽  
pp. 182-189 ◽  
Author(s):  
R. M. de Guia ◽  
M. D. J. Echavez ◽  
E. L. C. Gaw ◽  
M. R. R. Gomez ◽  
K. A. J. Lopez ◽  
...  
Keyword(s):  
Dimensionality Reduction ◽  
Multifactor Dimensionality Reduction ◽  
Gene Variants
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