Identification of epistasis in ischemic stroke using multifactor dimensionality reduction and entropy decomposition.
We investigated the genetic associations of ischemic stroke by identifying epistasis of its heterogeneous subtypes such as small vessel occlusion (SVO) and large artery atherosclerosis (LAA). Epistasis was analyzed with 24 genes in 207 controls and 271 patients (SVO = 110, LAA = 95) using multifactor dimensionality reduction and entropy decomposition. The multifactor dimensionality reduction analysis with any of 1- to 4-locus models showed no significant association with LAA (P > 0.05). The analysis of SVO, however, revealed a significant association in the best 3-locus model with P10L of TGF-beta1, C1013T of SPP1, and R485K of F5 (testing balanced accuracy = 63.17%, P < 0.05). Subsequent entropy analysis also revealed that such heterogeneity was present and quite a large entropy was estimated among the 3 loci for SVO (5.43%), but only a relatively small entropy was estimated for LAA (1.81%). This suggests that the synergistic epistasis model might contribute specifically to the pathogenetsis of SVO, which implies a different etiopathogenesis of the ischemic stroke subtypes. [BMB reports 2009; 42(9): 617-622].
Department of Bioinformatics and Life Science, Soongsil University, Seoul 156-743, Korea.
Jungdae
J
Park
Younyoung
Y
Kim
Chaeyoung
C
Lee
D000465:Algorithms; D050197:Atherosclerosis / Q000235:genetics; D002545:Brain Ischemia / Q000235:genetics*; D016022:Case-Control Studies; D019277:Entropy; D004843:Epistasis, Genetic / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D053495:Osteopontin / Q000235:genetics*; D020521:Stroke / Q000235:genetics*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
C506895:SPP1 protein, human; D053773:Transforming Growth Factor beta1; D053495:Osteopontin