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

doi:10.1016/j.bone.2009.09.025

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 journal › Article › peer-review

20 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 (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.

Original language	English (US)
Pages (from-to)	129-136
Number of pages	8
Journal	Bone
Volume	46
Issue number	1
DOIs	https://doi.org/10.1016/j.bone.2009.09.025
State	Published - 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
Physiology
Histology

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10.1016/j.bone.2009.09.025

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@article{b3e3a67010c548c8b80975dee44d56e9,

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

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.",

keywords = "Bone strength, EphrinA-EphR pathway, Femoral neck bone geometry, Genetic factor, Pathway-based genome-wide association analysis",

author = "Yuan Chen and Xiong, {Dong Hai} and Guo, {Yan Fang} and Feng Pan and Qi Zhou and Feng Zhang and Deng, {Hong Wen}",

note = "Funding Information: Investigators of this work were partially supported by grants from NIH ( R01 AR050496 , R21 AG027110 , R01 AG026564 , P50 AR055081 and R21 AA015973 ). The study also benefited from grants from National Science Foundation of China, Xi'an Jiaotong University, and the Ministry of Education of China. We also thank all contributors to the Framingham Heart Study. The Framingham Heart Study and the Framingham SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University. The Framingham SHARe data used for the analyses described in this manuscript were obtained through dbGaP. This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or the NHLBI.",

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doi = "10.1016/j.bone.2009.09.025",

language = "English (US)",

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T1 - Pathway-based genome-wide association analysis identified the importance of EphrinA-EphR pathway for femoral neck bone geometry

AU - Chen, Yuan

AU - Xiong, Dong Hai

AU - Guo, Yan Fang

AU - Pan, Feng

AU - Zhou, Qi

AU - Zhang, Feng

AU - Deng, Hong Wen

N1 - Funding Information: Investigators of this work were partially supported by grants from NIH ( R01 AR050496 , R21 AG027110 , R01 AG026564 , P50 AR055081 and R21 AA015973 ). The study also benefited from grants from National Science Foundation of China, Xi'an Jiaotong University, and the Ministry of Education of China. We also thank all contributors to the Framingham Heart Study. The Framingham Heart Study and the Framingham SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University. The Framingham SHARe data used for the analyses described in this manuscript were obtained through dbGaP. This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or the NHLBI.

PY - 2010/1

Y1 - 2010/1

N2 - 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.

AB - 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.

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

Abstract

Keywords

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