Pathway-based association analyses identified TRAIL pathway for osteoporotic fractures
Yin-Ping Zhang1, Yao-Zhong Liu, Yan Guo
1The Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University College of Medicine, Ministry of Education, Xi'an, Shaanxi, People's Republic of China. cathyzh@mail.xjtu.edu.cn
Insights
The Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) pathway is associated with hip Osteoporosis (OF) in the Chinese Han population. Specific genes within this pathway may influence osteoporosis risk and protection.
Area of Science:
- Genetics
- Bone Metabolism
- Molecular Biology
Background:
- Hip Osteoporosis (OF) is a significant cause of morbidity and mortality.
- Previous research suggests a link between the Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) pathway and bone metabolism.
- The specific role of the TRAIL pathway in hip OF pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the potential association between the TRAIL pathway and hip OF.
- To identify specific genes within the TRAIL pathway that may contribute to hip OF risk.
Main Methods:
- Genome-wide genotype data from Affymetrix 500K SNP arrays were analyzed.
- Pathway-based association analyses were conducted.
- The study included 700 elderly Chinese Han subjects (350 with hip OF and 350 controls).
Main Results:
- The TRAIL pathway showed a significant association with hip OF (p=0.01).
- Seven genes within the pathway were nominally associated with hip OF, with TNFSF10 (TRAIL) being the most significant (p=1.70×10(-4)).
- Specific SNPs in genes like TNFSF10 and TNFRSF10B were associated with increased hip OF risk, while others in CFLAR, NFKB1, TNFSF11, TNFRSF11A, and TRAF3 showed protective effects.
Conclusions:
- The TRAIL pathway plays a potential role in the pathogenesis of hip OF within the Chinese Han population.
- Further functional studies are warranted to elucidate the precise mechanisms by which the TRAIL pathway influences hip OF risk.
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.
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