title: High order gene-gene interactions in eight single nucleotide polymorphisms of renin-angiotensin system genes for hypertension association study.
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.
authors.affiliation: Department of Electronic Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung 80778, Taiwan.
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Department of Electronic Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung 80778, Taiwan.
authors.forename: Yu-Da
authors.initials: YD
authors.lastname: Lin
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Shyh-Jong
authors.identifier: 0000-0003-0371-7341
authors.initials: SJ
authors.lastname: Wu
authors.affiliation: Department of Chemical Engineering & Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung 84001, Taiwan.
authors.forename: Li-Yeh
authors.identifier: 0000-0002-9817-5102
authors.initials: LY
authors.lastname: Chuang
authors.affiliation: Cancer Center, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan ; Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan ; Research Center of Environmental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan ; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors.forename: Hsueh-Wei
authors.identifier: 0000-0003-0068-2366
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000368:Aged; D000808:Angiotensinogen / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D053263:Gene Regulatory Networks; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A