• Title/Summary/Keyword: multifactor-dimensionality reduction(MDR)

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Gene-gene interaction of CCND1, ESR1 and CDK7 on the risk of breast cancer detected by multifactor dimensionality reduction and logistic regression (유방암과 CCND1, ESR1, CDK7 유전자 다형성의 상호작용; 로지스틱 회귀분석과 multifactor dimensionality reduction(MDR)의 분석 비교)

  • Choe Ji-Yeop;Ritchie Marylyn D.;Motsinger Alison A.;Lee Gyeong-Mu;No Dong-Yeong;Yu Geun-Yeong;Moore Jason H.;Gang Dae-Hui
    • 대한예방의학회:학술대회논문집
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    • 2004.10a
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    • pp.40.1-40.1
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    • 2004
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Multifactor Dimensionality Reduction (MDR) Analysis to Detect Single Nucleotide Polymorphisms Associated with a Carcass Trait in a Hanwoo Population

  • Lee, Jea-Young;Kwon, Jae-Chul;Kim, Jong-Joo
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.6
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    • pp.784-788
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    • 2008
  • Studies to detect genes responsible for economic traits in farm animals have been performed using parametric linear models. A non-parametric, model-free approach using the 'expanded multifactor-dimensionality reduction (MDR) method' considering high dimensionalities of interaction effects between multiple single nucleotide polymorphisms (SNPs), was applied to identify interaction effects of SNPs responsible for carcass traits in a Hanwoo beef cattle population. Data were obtained from the Hanwoo Improvement Center, National Agricultural Cooperation Federation, Korea, and comprised 299 steers from 16 paternal half-sib proven sires that were delivered in Namwon or Daegwanryong livestock testing stations between spring of 2002 and fall of 2003. For each steer at approximately 722 days of age, the Longssimus dorsi muscle area (LMA) was measured after slaughter. Three functional SNPs (19_1, 18_4, 28_2) near the microsatellite marker ILSTS035 on BTA6, around which the QTL for meat quality were previously detected, were assessed. Application of the expanded MDR method revealed the best model with an interaction effect between the SNPs 19_1 and 28_2, while only one main effect of SNP19_1 was statistically significant for LMA (p<0.01) under a general linear mixed model. Our results suggest that the expanded MDR method better identifies interaction effects between multiple genes that are related to polygenic traits, and that the method is an alternative to the current model choices to find associations of multiple functional SNPs and/or their interaction effects with economic traits in livestock populations.

Important SNPs Identification from the Economic Traits for the High Quality Korean Cattle (고품질 한우를 위한 여러 경제형질에서의 주요 SNP 규명)

  • Lee, Jea-Young;Kim, Dong-Chul
    • Communications for Statistical Applications and Methods
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    • v.16 no.1
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    • pp.67-74
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    • 2009
  • In order to make the high quality Korean cattle, it has been identified the gene markers which influence to various economic traits. To identify statistically significances among SNP markers, Lee et. al. (2008b) identified SNP(19_1)$^*$SNP(28_2) marker was an important marker in LMA(longissimus muscle dorsi area). In addition, CWT(carcass cold weight) and ADG(average daily gain) are applied for expanded multifactor dimensionality reduction (expanded MDR) method from the comprehensive economic traits. The results showed that SNP(19_1)$^*$SNP(28_2) interaction marker was good and a very meaningful for economic traits.

An extension of multifactor dimensionality reduction method for detecting gene-gene interactions with the survival time (생존시간과 연관된 유전자 간의 교호작용에 관한 다중차원축소방법의 확장)

  • Oh, Jin Seok;Lee, Seung Yeoun
    • Journal of the Korean Data and Information Science Society
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    • v.25 no.5
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    • pp.1057-1067
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    • 2014
  • Many genetic variants have been identified to be associated with complex diseases such as hypertension, diabetes and cancers throughout genome-wide association studies (GWAS). However, there still exist a serious missing heritability problem since the proportion explained by genetic variants from GWAS is very weak less than 10~15%. Gene-gene interaction study may be helpful to explain the missing heritability because most of complex disease mechanisms are involved with more than one single SNP, which include multiple SNPs or gene-gene interactions. This paper focuses on gene-gene interactions with the survival phenotype by extending the multifactor dimensionality reduction (MDR) method to the accelerated failure time (AFT) model. The standardized residual from AFT model is used as a residual score for classifying multiple geno-types into high and low risk groups and algorithm of MDR is implemented. We call this method AFT-MDR and compares the power of AFT-MDR with those of Surv-MDR and Cox-MDR in simulation studies. Also a real data for leukemia Korean patients is analyzed. It was found that the power of AFT-MDR is greater than that of Surv-MDR and is comparable with that of Cox-MDR, but is very sensitive to the censoring fraction.

Support vector machine and multifactor dimensionality reduction for detecting major gene interactions of continuous data (서포트 벡터 머신 알고리즘을 활용한 연속형 데이터의 다중인자 차원축소방법 적용)

  • Lee, Jea-Young;Lee, Jong-Hyeong
    • Journal of the Korean Data and Information Science Society
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    • v.21 no.6
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    • pp.1271-1280
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    • 2010
  • We have used multifactor dimensionality reduction (MDR) method to study genegene interaction effect of statistical model in general. But, MDR method could not be applied in the continuous data. In this paper, continuous-type data by the support vector machine (SVM) algorithm are proposed to the MDR method which provides an introduction to the technique. Also we apply the method on the identify major interaction effects of single nucleotide polymorphisms (SNPs) responsible for economic traits in a Korean cattle population.

A study on interaction effect among risk factors of delirium using multifactor dimensionality reduction method

  • Lee, Jong-Hyeong;Lee, Yong-Won;Lee, Yoon-Seok;Lee, Jea-Young
    • Journal of the Korean Data and Information Science Society
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    • v.22 no.6
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    • pp.1257-1264
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    • 2011
  • Delirium is a neuropsychiatric disorder accompanying symptoms of hallucination, drowsiness, and tremors. It has high occurrence rates among elders, heart disease patients, and burn patients. It is a medical emergency associated with increased morbidity and mortality rates. That s why early detection and prevention of delirium ar significantly important. And This mental illness like delirium occurred by complex interaction between risk factors. In this paper, we identify risk factors and interactions between these factors for delirium using multi-factor dimensionality reduction (MDR) method.

Major gene interaction identification in Hanwoo by adjusted environmental effects (환경적인 요인을 보정한 한우의 우수 유전자 조합 선별)

  • Lee, Jea-Young;Jin, Mi-Hyun
    • Journal of the Korean Data and Information Science Society
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    • v.23 no.3
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    • pp.467-474
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    • 2012
  • Human diseases and livestock economic traits are not typically the result of variation of a single genetic locus, but are rather the result of interplay between interactions among multiple genes and a variety of environmental exposures. We have used linear regression model for adjusted environmental effects and multifactor dimensionality reduction (MDR) method to identify gene-gene interaction effect of statistical model in general. Of course, we use 5 SNPs (single uncleotide polymorphism) which were studied recently by Oh et al. (2011). We apply the MDR (multifactor demensionality reduction) method on the identify major interaction effects of single nucleotide polymorphisms responsible for economic traits in a Korean cattle population.

Identification of Stearoyl-CoA Desaturase (SCD) Gene Interactions in Korean Native Cattle Based on the Multifactor-dimensionality Reduction Method

  • Oh, Dong-Yep;Jin, Me-Hyun;Lee, Yoon-Seok;Ha, Jae-Jung;Kim, Byung-Ki;Yeo, Jung-Sou;Lee, Jea-Young
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.9
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    • pp.1218-1228
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    • 2013
  • Fat quality is determined by the composition of fatty acids. Genetic relationships between this composition and single nucleotide polymorphisms (SNPs) in the stearoyl-CoA desaturase1 (SCD1) gene were examined using 513 Korean native cattle. Single and epistatic effects of 7 SNP genetic variations were investigated, and the multifactor dimensionality reduction (MDR) method was used to investigate gene interactions in terms of oleic acid (C18:1), mono-unsaturated fatty acids (MUFAs) and marbling score (MS). The g.6850+77 A>G and g.14047 C>T SNP interactions were identified as the statistically optimal combination (C18:1, MUFAs and MS permutation p-values were 0.000, 0.000 and 0.001 respectively) of two-way gene interactions. The interaction effects of g.6850+77 A>G, g.10213 T>C and g.14047 C>T reflected the highest training-balanced accuracy (63.76%, 64.70% and 61.85% respectively) and was better than the individual effects for C18:1, MUFAs and MS. In addition, the superior genotype groups were AATTCC, AGTTCC, GGTCCC, AGTCCT, GGCCCT and AGCCTT. These results suggest that the selected SNP combination of the SCD1 gene and superior genotype groups can provide useful inferences for the improvement of the fatty acid composition in Korean native cattle.

Exploration of the Gene-Gene Interactions Using the Relative Risks in Distinct Genotypes (유전자형별 상대 위험도를 이용한 유전자-유전자간 상호작용 탐색)

  • Jung, Ji-Won;Yee, Jae-Yong;Lee, Suk-Hoon;Pa, Mi-Ra
    • The Korean Journal of Applied Statistics
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    • v.24 no.5
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    • pp.861-869
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    • 2011
  • One of the main objects of recent genetic studies is to understand genetic factors that induce complex diseases. If there are interactions between loci, it is difficult to find such associations through a single-locus analysis strategy. Thus we need to consider the gene-gene interactions and/or gene-environment interactions. The MDR(multifactor dimensionality reduction) method is being used frequently; however, it is not appropriate to detect interactions caused by a small fraction of the possible genotype pairs. In this study, we propose a relative risk interaction explorer that detects interactions through the calculation of the relative risks between the control and disease groups from each genetic combinations. For illustration, we apply this method to MDR open source data. We also compare the MDR and the proposed method using the simulated data eight genetic models.

Network Graph Analysis of Gene-Gene Interactions in Genome-Wide Association Study Data

  • Lee, Sungyoung;Kwon, Min-Seok;Park, Taesung
    • Genomics & Informatics
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    • v.10 no.4
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    • pp.256-262
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    • 2012
  • Most common complex traits, such as obesity, hypertension, diabetes, and cancers, are known to be associated with multiple genes, environmental factors, and their epistasis. Recently, the development of advanced genotyping technologies has allowed us to perform genome-wide association studies (GWASs). For detecting the effects of multiple genes on complex traits, many approaches have been proposed for GWASs. Multifactor dimensionality reduction (MDR) is one of the powerful and efficient methods for detecting high-order gene-gene ($G{\times}G$) interactions. However, the biological interpretation of $G{\times}G$ interactions identified by MDR analysis is not easy. In order to aid the interpretation of MDR results, we propose a network graph analysis to elucidate the meaning of identified $G{\times}G$ interactions. The proposed network graph analysis consists of three steps. The first step is for performing $G{\times}G$ interaction analysis using MDR analysis. The second step is to draw the network graph using the MDR result. The third step is to provide biological evidence of the identified $G{\times}G$ interaction using external biological databases. The proposed method was applied to Korean Association Resource (KARE) data, containing 8838 individuals with 327,632 single-nucleotide polymorphisms, in order to perform $G{\times}G$ interaction analysis of body mass index (BMI). Our network graph analysis successfully showed that many identified $G{\times}G$ interactions have known biological evidence related to BMI. We expect that our network graph analysis will be helpful to interpret the biological meaning of $G{\times}G$ interactions.