Summarizing techniques that combine three non-parametric scores to detect disease-associated 2-way SNP-SNP interactions.
Journal
Gene
Journal Volume
533
Journal Issue
1
Start Page
304-12
ISSN
1879-0038
Date Issued
2014-01-01
Author(s)
Abstract
Identifying 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.
Subjects
APD
APD score
APDS
BDNF
C5
CART
CASP 9
CCP
CV
ES
GAW16
GS
GWAS
Gini score
HLA
HLA-DQB1
HLA-DRB1
KEGG
LD
MAF
MDR
Max
NARAC
NN
NTRK2
Non-parametric methods
North American Rheumatoid Arthritis Consortium
PC1
PCS
PIA
PTPN22
QC
RA
RASSUN
RAnked Summarized Scores Using Non-parametric-methods
Rheumatoid arthritis (RA)
SNP
SNP-SNP interaction
SS
SSS
Single-nucleotide-polymorphism (SNP)
Std Dev
Summary scores
TNF-receptor-associated factor 1
TRAF1
Z-score
Z-sum score
ZS
ZSS
absolute probability difference
brain derived neurotrophic factor
caspase 9
classification and regression trees
compliment component
cross-validation
cyclic citrullinated peptide
entropy score
genetic- analysis-workshop 16
genome wide association study
human leukocyte antigens
kyoto encyclopedia of genes and genomes
linkage disequilibrium
major hiscompatibility complex class II, DQ beta 1
major hiscompatibility complex class II, DR beta 1
maximum
minor allele frequency
multifactor dimensionality reduction
neural networks
neurotrophic tyrosine kinase, receptor, type 2
polymorphism interaction analysis
principal component 1
principle component score
protein tyrosine phosphatase, non-receptor type 22 lymphoid
quality control
rheumatoid arthritis
scaled score
single-nucleotide-polymorphism
standard deviation
sum of scaled scores
Type
journal article