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High order gene-gene interactions in eight single nucleotide polymorphisms of renin-angiotensin system genes for hypertension association study.

Yang CH, Lin YD, Wu SJ, Chuang LY, Chang HW - Biomed Res Int (2015)

Bottom Line: Several single nucleotide polymorphisms (SNPs) of renin-angiotensin system (RAS) genes are associated with hypertension (HT) but most of them are focusing on single locus effects.In 7- and 8-locus model, SNP A1166C of AT 1 R gene is joined to improve the maximum Boot-OR values of 4.050 to 4.483; CI = 2.49 to 7.29; P < 1.63E - 08.In conclusion, the epistasis networks are identified by eight SNP-SNP interaction models.

View Article: PubMed Central - PubMed

Affiliation: Department of Electronic Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung 80778, Taiwan.

ABSTRACT
Several single nucleotide polymorphisms (SNPs) of renin-angiotensin system (RAS) genes are associated with hypertension (HT) but most of them are focusing on single locus effects. Here, we introduce an unbalanced function based on multifactor dimensionality reduction (MDR) for multiloci genotypes to detect high order gene-gene (SNP-SNP) interaction in unbalanced cases and controls of HT data. Eight SNPs of three RAS genes (angiotensinogen, AGT; angiotensin-converting enzyme, ACE; angiotensin II type 1 receptor, AT 1 R) in HT and non-HT subjects were included that showed no significant genotype differences. In 2- to 6-locus models of the SNP-SNP interaction, the SNPs of AGT and ACE genes were associated with hypertension (bootstrapping odds ratio [Boot-OR] = 1.972~3.785; 95%, confidence interval (CI) 1.26~6.21; P < 0.005). In 7- and 8-locus model, SNP A1166C of AT 1 R gene is joined to improve the maximum Boot-OR values of 4.050 to 4.483; CI = 2.49 to 7.29; P < 1.63E - 08. In conclusion, the epistasis networks are identified by eight SNP-SNP interaction models. AGT, ACE, and AT 1 R genes have overall effects with susceptibility to hypertension, where the SNPs of ACE have a mainly hypertension-associated effect and show an interacting effect to SNPs of AGT and AT 1 R genes.

No MeSH data available.


Related in: MedlinePlus

Epistasis networks of the best 2- to 8-locus models for SNP-SNP interaction are associated with hypertension. Significant gene-gene interactions (P < 0.05) in these multifoci models are connected by blue lines, and the strength of interaction is labeled with OR values. The thicker and thinner lines represent the higher and lower interactions, respectively.
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fig3: Epistasis networks of the best 2- to 8-locus models for SNP-SNP interaction are associated with hypertension. Significant gene-gene interactions (P < 0.05) in these multifoci models are connected by blue lines, and the strength of interaction is labeled with OR values. The thicker and thinner lines represent the higher and lower interactions, respectively.

Mentions: The SNP-SNP interaction networks (Table 4) have further been validated by the single-SNP-to-single-SNP interaction analyses (Figure 3) for the best 2- to 8-locus models in terms of OR values. SNPs involved in one or more significant interactions are represented as nodes, and the pairs of SNPs with significant interactions are connected by lines. For example, all SNPs are significantly associated with ACE I/D, suggesting that ACE I/D is mainly associated with hypertension. The G-217A and ACE I/D are integrated to the best 2-locus model. The G-6A is further integrated to the best 3-locus model and it is validated that G-6A has positively interacted with G-217A and ACE I/D (OR > 1). Similarly, the other newly integrated SNPs in each multiloci model have positively interacted with the previous SNPs in each multiloci model.


High order gene-gene interactions in eight single nucleotide polymorphisms of renin-angiotensin system genes for hypertension association study.

Yang CH, Lin YD, Wu SJ, Chuang LY, Chang HW - Biomed Res Int (2015)

Epistasis networks of the best 2- to 8-locus models for SNP-SNP interaction are associated with hypertension. Significant gene-gene interactions (P < 0.05) in these multifoci models are connected by blue lines, and the strength of interaction is labeled with OR values. The thicker and thinner lines represent the higher and lower interactions, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4417588&req=5

fig3: Epistasis networks of the best 2- to 8-locus models for SNP-SNP interaction are associated with hypertension. Significant gene-gene interactions (P < 0.05) in these multifoci models are connected by blue lines, and the strength of interaction is labeled with OR values. The thicker and thinner lines represent the higher and lower interactions, respectively.
Mentions: The SNP-SNP interaction networks (Table 4) have further been validated by the single-SNP-to-single-SNP interaction analyses (Figure 3) for the best 2- to 8-locus models in terms of OR values. SNPs involved in one or more significant interactions are represented as nodes, and the pairs of SNPs with significant interactions are connected by lines. For example, all SNPs are significantly associated with ACE I/D, suggesting that ACE I/D is mainly associated with hypertension. The G-217A and ACE I/D are integrated to the best 2-locus model. The G-6A is further integrated to the best 3-locus model and it is validated that G-6A has positively interacted with G-217A and ACE I/D (OR > 1). Similarly, the other newly integrated SNPs in each multiloci model have positively interacted with the previous SNPs in each multiloci model.

Bottom Line: Several single nucleotide polymorphisms (SNPs) of renin-angiotensin system (RAS) genes are associated with hypertension (HT) but most of them are focusing on single locus effects.In 7- and 8-locus model, SNP A1166C of AT 1 R gene is joined to improve the maximum Boot-OR values of 4.050 to 4.483; CI = 2.49 to 7.29; P < 1.63E - 08.In conclusion, the epistasis networks are identified by eight SNP-SNP interaction models.

View Article: PubMed Central - PubMed

Affiliation: Department of Electronic Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung 80778, Taiwan.

ABSTRACT
Several single nucleotide polymorphisms (SNPs) of renin-angiotensin system (RAS) genes are associated with hypertension (HT) but most of them are focusing on single locus effects. Here, we introduce an unbalanced function based on multifactor dimensionality reduction (MDR) for multiloci genotypes to detect high order gene-gene (SNP-SNP) interaction in unbalanced cases and controls of HT data. Eight SNPs of three RAS genes (angiotensinogen, AGT; angiotensin-converting enzyme, ACE; angiotensin II type 1 receptor, AT 1 R) in HT and non-HT subjects were included that showed no significant genotype differences. In 2- to 6-locus models of the SNP-SNP interaction, the SNPs of AGT and ACE genes were associated with hypertension (bootstrapping odds ratio [Boot-OR] = 1.972~3.785; 95%, confidence interval (CI) 1.26~6.21; P < 0.005). In 7- and 8-locus model, SNP A1166C of AT 1 R gene is joined to improve the maximum Boot-OR values of 4.050 to 4.483; CI = 2.49 to 7.29; P < 1.63E - 08. In conclusion, the epistasis networks are identified by eight SNP-SNP interaction models. AGT, ACE, and AT 1 R genes have overall effects with susceptibility to hypertension, where the SNPs of ACE have a mainly hypertension-associated effect and show an interacting effect to SNPs of AGT and AT 1 R genes.

No MeSH data available.


Related in: MedlinePlus