Pathway-based genome-wide association analysis identified the importance of EphrinA-EphR pathway for femoral neck bone geometry.
Femoral neck (FN) bone geometry is an important predictor of bone strength with high heritability. Previous studies have revealed certain candidate genes for FN bone geometry. However, the majority of the underlying genetic factors remain to be discovered. In this study, pathway-based genome-wide association analysis was performed to explore the joint effects of genes within biological pathways on FN bone geometry variations in a cohort of 1000 unrelated US whites. Nominal significant associations (nominal p value<0.05) were observed between 76 pathways and a key FN bone geometry variable-section modulus (Z), biomechanically indicative of bone strength subject to bending. Among them, EphrinA-EphR pathway was most significantly associated with FN Z even after multiple testing adjustments (p(FWER) value=0.035). The association of EphrinA-EphR pathway with FN Z was also observed in an independent sample from Framingham Osteoporosis Study. Overall, these results suggest the significant genetic contribution of EphrinA-EphR pathway to femoral neck bone geometry.
The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, PR China.
Yuan
Y
Chen
Dong-Hai
DH
Xiong
Yan-Fang
YF
Guo
Feng
F
Pan
Qi
Q
Zhou
Feng
F
Zhang
Hong-Wen
HW
Deng
D000328:Adult; D000368:Aged; D036342:Ephrins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005272:Femur Neck / Q000378:metabolism*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D036342:Ephrins