Multifactor dimensionality reduction reveals gene–gene interactions associated with multiple sclerosis susceptibility in African Americans

Brassat, David; Motsinger, Alison A.; Caillier, Stacy J.; Erlich, Henry A.; Walker, Karen; Steiner, Lori; Cree, Bruce A.C.; Barcellos, Lisa F.; Pericak‐Vance, M. A.; Schmidt, Silke; Gregory, Simon G.; Haines, Jonathan L.; Oksenberg, Jorge R.; Ritchie, Marylyn D.

doi:10.1038/sj.gene.6364299

Cited by 48 publications

(33 citation statements)

References 31 publications

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“…The calculations were performed, using MDR software (www.epistasis.org). Interaction dendrograms 39,42,43 were created to view graphical representation of interactions between variables and to assess the statistical nature of relationship between markers (redundant, additive or synergistic).…”

Section: Discussionmentioning

confidence: 99%

DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans

et al. 2007

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We investigated the role of DC-SIGN (CD209), long pentraxin 3 (PTX3) and vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) in susceptibility to pulmonary tuberculosis (TB) in 321 TB cases and 347 healthy controls from GuineaBissau. Five additional, functionally relevant SNPs within toll-like receptors (TLRs) 2, 4 and 9 were typed but found, when polymorphic, not to affect host vulnerability to pulmonary TB. We did not replicate an association between SNPs in the DC-SIGN promoter and TB. However, we found that two polymorphisms, one in DC-SIGN and one in VDR, were associated in a nonadditive model with disease risk when analyzed in combination with ethnicity (P ¼ 0.03 for DC-SIGN and P ¼ 0.003 for VDR). In addition, PTX3 haplotype frequencies significantly differed in cases compared to controls and a protective effect was found in association with a specific haplotype (OR 0.78, 95% CI 0.63-0.98). Our findings support previous data showing that VDR SNPs modulate the risk for TB in West Africans and suggest that variation within DC-SIGN and PTX3 also affect the disease outcome.

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Section: Discussionmentioning

confidence: 99%

DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans

et al. 2007

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“…For I75V it is suggested that homozygosity for the V-allele associates with slow progression from HIV-1 to AIDS 45 and that the V-allele increases the risk of erosive disease in rheumatoid arthritis. 46 The Q576R polymorphism is suggested to have implications for susceptibility to HIV-1 infection 47 and multiple sclerosis 48,49 and IL-4R haplotypes have shown association with Type 1 diabetes. 35,38 If the I75V polymorphism alters T H 1/T H 2 balance, it may influence susceptibility to persistent HPV-infection and cancer, assuming that a T H 1 response is essential for HPV clearance.…”

Section: Discussionmentioning

confidence: 99%

Variants of chemokine receptor 2 and interleukin 4 receptor, but not interleukin 10 or Fas ligand, increase risk of cervical cancer

Ivansson

Gustavsson

Magnusson

et al. 2007

Intl Journal of Cancer

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Cervical cancer is caused by persistent infection of oncogenic human papillomavirus (HPV). Most infected women clear the virus without developing cervical lesions and it is likely that immunological host factors affect susceptibility to cervical cancer. The impact of the human leukocyte antigen (HLA) locus on the risk of cervical cancer is established and several other genes involved in immunological pathways have been suggested as biologically plausible candidates. The aim of this study was to examine the potential role of polymorphisms in 4 candidate genes by analysis of 1,306 familial cervical cancer cases and 288 controls. The following genes and polymorphisms were studied: Chemokine receptor 2 (CCR-2) V64I; Interleukin 4 receptor a (IL-4R) I75V, S503P and Q576R; Interleukin 10 (IL-10) 2592; and Fas ligand (FasL) 2844. The CCR-2 64I variant was associated with decreased risk of cervical cancer; homozygote carriers of the 64I variant had an odds ratio of 0.31 (0.12-0.77). This association was detected in both carriers and noncarriers of the HLA DQB1*0602 cervical cancer risk allele. The IL-4R 75V variant was associated with increased risk of cervical tumors, cases homozygote for 75V had an odds ratio of 1.91 (1.27-2.86) with a tendency that the association was stronger in noncarriers of the DQB1*0602 allele. We did not find any association for IL-10 2592, or FasL 2844, previously reported to be associated with cervical cancer in the Dutch and Chinese populations, respectively. ' 2007 Wiley-Liss, Inc.

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“…These SNP-based methods, such as logistic regression analysis, MDR, 8 Gene-based association study explicitly accounts for biological function of a gene, so it takes the problem of nonreplication up to the gene level. Effectively, gene-based association study alleviates the burden of multiple testing in into two stages: handling of multiple variants within a gene and multiple genes across the genome.…”

Section: Discussionmentioning

confidence: 99%

“…7 Several methods for detection of gene-gene interaction are worthy of note. In particular, multifactor dimensionality reduction (MDR) 8 is a data-mining method [8][9][10][11][12][13][14] However, the heavy dependence on data structure, complicated procedure and lack of clear biological interpretation of the detected gene-gene interactions had limited applications of data-mining methods in complex disease association study. 7 Parametric methods are more powerful than nonparametric methods provided valid assumptions are made.…”

Section: Introductionmentioning

confidence: 99%

A gene-based method for detecting gene–gene co-association in a case–control association study

2009

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Association study (especially the genome-wide association study) now has a key function in identification and characterization of disease-predisposing genetic variant(s), which customarily involve multiple single nucleotide polymorphisms (SNPs) in a candidate region or across the genome. Case-control association design remains the most popular and a challenging issue in the statistical analysis is the optimal use of all information contained in these SNPs. Previous approaches often treated gene-gene interaction as deviation from additive genetic effects or replaced it with SNP-SNP interaction. However, these approaches are limited for their failure of consideration of gene-gene interaction or gene-gene co-association at gene level. Although the co-association of the SNPs within a candidate gene can be detected by principal component analysis-based logistic regression model, the detection of co-association between genes in genome remains uncertain. Here, we proposed a canonical correlationbased U statistic (CCU) for detecting gene-based gene-gene co-association in the case-control design. We explored its type I error rates and power through simulation and analyzed two real data sets. By treating gene as a functional unit in analysis, we found that CCU was a strong alternative to previous approaches. We discussed the performance of CCU as a gene-based gene-gene co-association statistic and the prospect of further improvement.

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Multifactor dimensionality reduction reveals gene–gene interactions associated with multiple sclerosis susceptibility in African Americans

Cited by 48 publications

References 31 publications

DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans

DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans

Variants of chemokine receptor 2 and interleukin 4 receptor, but not interleukin 10 or Fas ligand, increase risk of cervical cancer

A gene-based method for detecting gene–gene co-association in a case–control association study

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