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Title: Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures
Authors: Zhang Y.-P.
Liu Y.-Z.
Guo Y.
Liu X.-G. 
Xu X.-H.
Guo Y.-F.
Chen Y.
Zhang F.
Pan F.
Zhu X.-Z.
Deng H.-W.
Keywords: adult
CFLAR gene
controlled study
fragility fracture
gene frequency
gene function
genetic association
genetic risk
genome analysis
hip fracture
major clinical study
molecular pathology
NFKB1 gene
single nucleotide polymorphism
TNFRSF10B gene
TNFRSF11A gene
TNFSF10 gene
TNFSF11 gene
TRAF3 gene
TRAIL gene
fragility fracture
genetic predisposition
signal transduction
tumor necrosis factor related apoptosis inducing ligand
Genetic Predisposition to Disease
Osteoporotic Fractures
Polymorphism, Single Nucleotide
Signal Transduction
TNF-Related Apoptosis-Inducing Ligand
Issue Date: 2011
Citation: Zhang Y.-P., Liu Y.-Z., Guo Y., Liu X.-G., Xu X.-H., Guo Y.-F., Chen Y., Zhang F., Pan F., Zhu X.-Z., Deng H.-W. (2011). Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures. PLoS ONE 6 (7) : e21835. ScholarBank@NUS Repository.
Abstract: Introduction: Hip OF carries the highest morbidity and mortality. Previous studies revealed that individual genes/loci in the Tumor Necrosis Factor (TNF) -Related Apoptosis-Inducing Ligand (TRAIL) pathway were associated with bone metabolism. This study aims to verify the potential association between hip OF and TRAIL pathway. Methods: Using genome-wide genotype data from Affymetrix 500 K SNP arrays, we performed novel pathway-based association analyses for hip OF in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls). Results: The TRAIL pathway achieved a significant p value (p = 0.01) for association with hip OF. Among the 38 genes in the TRAIL pathway, seven genes achieved nominally significant association with hip OF (p<0.05); the TNFSF10 (TRAIL) gene obtained the most significant p value (p = 1.70×10 -4 ). SNPs (rs719126, rs6533015, rs9594738, rs1805034, rs11160706) from five genes (CFLAR, NFKB1, TNFSF11, TNFRSF11A, TRAF3) of the pathway had minor alleles that appear to be protective to hip OF. SNPs (rs6445063 and rs4259415) from two genes (TNFSF10 and TNFRSF10B) of the pathway had minor alleles (A) that are associated with an increased risk of hip OF, with the ORs (odds ratios) of 16.51 (95%CI:3.83-71.24) and 1.37 (95%CI:1.08-1.74), respectively. Conclusions: Our study supports the potential role of the TRAIL pathway in the pathogenesis of hip OF in Chinese Han population. Further functional study of this pathway will be pursued to determine the mechanism by which it confers risk to hip OF. © 2011 Zhang et al.
Source Title: PLoS ONE
ISSN: 19326203
DOI: 10.1371/journal.pone.0021835
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