Preventive SNP-SNP interactions in the mitochondrial displacement loop (D-loop) from chronic dialysis patients.

Chronic dialysis association study involving individual single nucleotide polymorphisms (SNPs) in the mitochondrial displacement loop (D-loop) has previously been reported. However, possible SNP-SNP interactions for SNPs in the D-loop which could be associated with a reduced risk for chronic dialysis were not investigated. The purpose of this study was to propose an effective algorithm to identify protective SNP-SNP interactions in the D-loop from chronic dialysis patients. We introduce ISGA that uses an initialization strategy for genetic algorithms (GA) to improve the computational analysis for protective SNP-SNP interactions. ISGA generates genotype patterns with combined SNPs (SNP barcodes) for chronic dialysis. Using our previously reported 77 SNPs in the D-loop, the algorithm-generated protective SNP barcodes for chronic dialysis were evaluated. ISGA provides the SNP barcodes with the maximum frequency differences of occurrence between the cases and controls. The identified SNP barcodes with the lowest odds ratio (OR) values were regarded as the best preventive SNP barcodes against chronic dialysis. The best ISGA-generated SNP barcodes (two to nine SNPs) are more closely associated with the prevention of chronic dialysis when more SNPs are chosen (OR=0.64 to 0.32; 95% confidence interval=0.882 to 0.198). The cumulative effects of SNP-SNP interactions were more dominant in ISGA rather than in GA without the initialization strategy. We provide a fast identification of chronic dialysis-associated protective SNP barcodes and demonstrate that the SNP-SNP interactions may have a cumulative effect on prediction for chronic dialysis.