Pathway-based genome-wide association analysis identified the importance of EphrinA-EphR pathway for femoral neck bone geometry

Yuan Chen, Dong Hai Xiong, Yan Fang Guo, Feng Pan, Qi Zhou, Feng Zhang, Hong Wen Deng

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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 (pFWER 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.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalBone
Volume46
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Bone strength
  • EphrinA-EphR pathway
  • Femoral neck bone geometry
  • Genetic factor
  • Pathway-based genome-wide association analysis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

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