Summarizing techniques that combine three non-parametric scores to detect disease-associated 2-way SNP-SNP interactions.

Amrita ChattopadhyayHsiao, Ching-LinChing-LinHsiaoChang, Chien ChingChien ChingChangLian, Ie-BinIe-BinLianFann, Cathy S JCathy S JFann2026-04-102026-04-102014-01-01https://scholars.lib.ntu.edu.tw/handle/123456789/737090Identifying susceptibility genes that influence complex diseases is extremely difficult because loci often influence the disease state through genetic interactions. Numerous approaches to detect disease-associated SNP-SNP interactions have been developed, but none consistently generates high-quality results under different disease scenarios. Using summarizing techniques to combine a number of existing methods may provide a solution to this problem. Here we used three popular non-parametric methods-Gini, absolute probability difference (APD), and entropy-to develop two novel summary scores, namely principle component score (PCS) and Z-sum score (ZSS), with which to predict disease-associated genetic interactions. We used a simulation study to compare performance of the non-parametric scores, the summary scores, the scaled-sum score (SSS; used in polymorphism interaction analysis (PIA)), and the multifactor dimensionality reduction (MDR). The non-parametric methods achieved high power, but no non-parametric method outperformed all others under a variety of epistatic scenarios. PCS and ZSS, however, outperformed MDR. PCS, ZSS and SSS displayed controlled type-I-errors (<0.05) compared to GS, APDS, ES (>0.05). A real data study using the genetic-analysis-workshop 16 (GAW 16) rheumatoid arthritis dataset identified a number of interesting SNP-SNP interactions.enAPDAPD scoreAPDSBDNFC5CARTCASP 9CCPCVESGAW16GSGWASGini scoreHLAHLA-DQB1HLA-DRB1KEGGLDMAFMDRMaxNARACNNNTRK2Non-parametric methodsNorth American Rheumatoid Arthritis ConsortiumPC1PCSPIAPTPN22QCRARASSUNRAnked Summarized Scores Using Non-parametric-methodsRheumatoid arthritis (RA)SNPSNP-SNP interactionSSSSSSingle-nucleotide-polymorphism (SNP)Std DevSummary scoresTNF-receptor-associated factor 1TRAF1Z-scoreZ-sum scoreZSZSSabsolute probability differencebrain derived neurotrophic factorcaspase 9classification and regression treescompliment componentcross-validationcyclic citrullinated peptideentropy scoregenetic- analysis-workshop 16genome wide association studyhuman leukocyte antigenskyoto encyclopedia of genes and genomeslinkage disequilibriummajor hiscompatibility complex class II, DQ beta 1major hiscompatibility complex class II, DR beta 1maximumminor allele frequencymultifactor dimensionality reductionneural networksneurotrophic tyrosine kinase, receptor, type 2polymorphism interaction analysisprincipal component 1principle component scoreprotein tyrosine phosphatase, non-receptor type 22 lymphoidquality controlrheumatoid arthritisscaled scoresingle-nucleotide-polymorphismstandard deviationsum of scaled scoresSummarizing techniques that combine three non-parametric scores to detect disease-associated 2-way SNP-SNP interactions.journal article10.1016/j.gene.2013.09.04124076437