Proximal hip geometry is linked to several chromosomal regions: Genome-wide linkage results from the Framingham Osteoporosis Study

S. Demissie; J. Dupuis; L. A. Cupples; T. J. Beck; D. P. Kiel; D. Karasik

doi:10.1016/j.bone.2006.09.020

Proximal hip geometry is linked to several chromosomal regions: Genome-wide linkage results from the Framingham Osteoporosis Study

S. Demissie, J. Dupuis, L. A. Cupples, T. J. Beck, D. P. Kiel, D. Karasik

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

Introduction: Femoral geometry contributes to bone strength and predicts hip fracture risk. The purpose of this study was to evaluate heritability (h²) of geometric indices of the proximal hip and to perform whole-genome linkage analyses of these traits, adjusted for body size. Methods: DXA scans of the proximal femur from 1473 members of 323 pedigrees (age range 31-96 years) from the population-based Framingham Osteoporosis Study were obtained. Using the hip structural analysis program, we measured femoral neck length (FNL, cm) and neck-shaft angle (NSA); subperiosteal width (WID, cm), cross-sectional area (CSA, cm²); and section modulus (Z, cm³) at the narrowest section of the neck (NN), intertrochanteric (IT) and femoral shaft (S) regions. Linkage analyses were performed for the above indices with a set of 636 markers using variance components maximum likelihood method. Results: Substantial genetic influences were found for all geometric phenotypes, with h² values between 0.28 (NSA) and 0.70 (IT_WID). Adjustment for height and BMI did not alter h² of NSA and FNL but decreased h² of the cross-sectional indices. We obtained substantial linkage (multipoint LOD > 3.0) for S_Z at 2p21 and 21q11 and S_WID at Xq25-q26. Inclusion of height and BMI as covariates resulted in much lower LOD scores for S_Z, whereas linkage signals for S_Z at 4q25, S_CSA at 4q32 and S_CSA and S_Z at 15q21 increased after the adjustment. Linkage of FNL at 1q and 13q, NSA at 2q and NN_WID at 16q did not change after the adjustment. Conclusion: Suggestive linkages of bone geometric indices were found at 1q, 2p, 4q, 13q, 15q and Xq. The identification of significant linkage regions after adjustment for BMI and height may point to QTLs influencing femoral bone geometry independent of body size.

Original language	English
Pages (from-to)	743-750
Number of pages	8
Journal	Bone
Volume	40
Issue number	3
DOIs	https://doi.org/10.1016/j.bone.2006.09.020
State	Published - Mar 2007
Externally published	Yes

Bibliographical note

Funding Information:
From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), the National Institute of Arthritis, Musculoskeletal and Skin Diseases and the National Institute on Aging (grants No. R01-AR050066 and R01-AR/AG 41398). We gratefully acknowledge the Framingham Study members who participated in this study, as well as the study coordinators, who contributed to the success of this work. We would like also to express our thanks to Drs. L. Havill, M. Mahaney and M. Bouxsein for their useful suggestions in performing the analysis for the manuscript and Ms. Sophia Menn and Mei Lu for their help with data preparation and figures.

Funding

From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), the National Institute of Arthritis, Musculoskeletal and Skin Diseases and the National Institute on Aging (grants No. R01-AR050066 and R01-AR/AG 41398). We gratefully acknowledge the Framingham Study members who participated in this study, as well as the study coordinators, who contributed to the success of this work. We would like also to express our thanks to Drs. L. Havill, M. Mahaney and M. Bouxsein for their useful suggestions in performing the analysis for the manuscript and Ms. Sophia Menn and Mei Lu for their help with data preparation and figures.

Funders	Funder number
National Institute on Aging
National Heart, Lung, and Blood Institute	N01-HC-25195
National Institute of Arthritis and Musculoskeletal and Skin Diseases	R01AR041398

Keywords

Body size and body composition
Geometry
Heritability
Proximal femur
Quantitative trait loci
Whole-genome linkage

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bone.2006.09.020

Cite this

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title = "Proximal hip geometry is linked to several chromosomal regions: Genome-wide linkage results from the Framingham Osteoporosis Study",

abstract = "Introduction: Femoral geometry contributes to bone strength and predicts hip fracture risk. The purpose of this study was to evaluate heritability (h2) of geometric indices of the proximal hip and to perform whole-genome linkage analyses of these traits, adjusted for body size. Methods: DXA scans of the proximal femur from 1473 members of 323 pedigrees (age range 31-96 years) from the population-based Framingham Osteoporosis Study were obtained. Using the hip structural analysis program, we measured femoral neck length (FNL, cm) and neck-shaft angle (NSA); subperiosteal width (WID, cm), cross-sectional area (CSA, cm2); and section modulus (Z, cm3) at the narrowest section of the neck (NN), intertrochanteric (IT) and femoral shaft (S) regions. Linkage analyses were performed for the above indices with a set of 636 markers using variance components maximum likelihood method. Results: Substantial genetic influences were found for all geometric phenotypes, with h2 values between 0.28 (NSA) and 0.70 (IT_WID). Adjustment for height and BMI did not alter h2 of NSA and FNL but decreased h2 of the cross-sectional indices. We obtained substantial linkage (multipoint LOD > 3.0) for S_Z at 2p21 and 21q11 and S_WID at Xq25-q26. Inclusion of height and BMI as covariates resulted in much lower LOD scores for S_Z, whereas linkage signals for S_Z at 4q25, S_CSA at 4q32 and S_CSA and S_Z at 15q21 increased after the adjustment. Linkage of FNL at 1q and 13q, NSA at 2q and NN_WID at 16q did not change after the adjustment. Conclusion: Suggestive linkages of bone geometric indices were found at 1q, 2p, 4q, 13q, 15q and Xq. The identification of significant linkage regions after adjustment for BMI and height may point to QTLs influencing femoral bone geometry independent of body size.",

keywords = "Body size and body composition, Geometry, Heritability, Proximal femur, Quantitative trait loci, Whole-genome linkage",

author = "S. Demissie and J. Dupuis and Cupples, {L. A.} and Beck, {T. J.} and Kiel, {D. P.} and D. Karasik",

note = "Funding Information: From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), the National Institute of Arthritis, Musculoskeletal and Skin Diseases and the National Institute on Aging (grants No. R01-AR050066 and R01-AR/AG 41398). We gratefully acknowledge the Framingham Study members who participated in this study, as well as the study coordinators, who contributed to the success of this work. We would like also to express our thanks to Drs. L. Havill, M. Mahaney and M. Bouxsein for their useful suggestions in performing the analysis for the manuscript and Ms. Sophia Menn and Mei Lu for their help with data preparation and figures. ",

year = "2007",

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doi = "10.1016/j.bone.2006.09.020",

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TY - JOUR

T1 - Proximal hip geometry is linked to several chromosomal regions

T2 - Genome-wide linkage results from the Framingham Osteoporosis Study

AU - Demissie, S.

AU - Dupuis, J.

AU - Cupples, L. A.

AU - Beck, T. J.

AU - Kiel, D. P.

AU - Karasik, D.

N1 - Funding Information: From the Framingham Heart Study of the National Heart Lung and Blood Institute of the National Institutes of Health and Boston University School of Medicine. This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (Contract No. N01-HC-25195), the National Institute of Arthritis, Musculoskeletal and Skin Diseases and the National Institute on Aging (grants No. R01-AR050066 and R01-AR/AG 41398). We gratefully acknowledge the Framingham Study members who participated in this study, as well as the study coordinators, who contributed to the success of this work. We would like also to express our thanks to Drs. L. Havill, M. Mahaney and M. Bouxsein for their useful suggestions in performing the analysis for the manuscript and Ms. Sophia Menn and Mei Lu for their help with data preparation and figures.

PY - 2007/3

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N2 - Introduction: Femoral geometry contributes to bone strength and predicts hip fracture risk. The purpose of this study was to evaluate heritability (h2) of geometric indices of the proximal hip and to perform whole-genome linkage analyses of these traits, adjusted for body size. Methods: DXA scans of the proximal femur from 1473 members of 323 pedigrees (age range 31-96 years) from the population-based Framingham Osteoporosis Study were obtained. Using the hip structural analysis program, we measured femoral neck length (FNL, cm) and neck-shaft angle (NSA); subperiosteal width (WID, cm), cross-sectional area (CSA, cm2); and section modulus (Z, cm3) at the narrowest section of the neck (NN), intertrochanteric (IT) and femoral shaft (S) regions. Linkage analyses were performed for the above indices with a set of 636 markers using variance components maximum likelihood method. Results: Substantial genetic influences were found for all geometric phenotypes, with h2 values between 0.28 (NSA) and 0.70 (IT_WID). Adjustment for height and BMI did not alter h2 of NSA and FNL but decreased h2 of the cross-sectional indices. We obtained substantial linkage (multipoint LOD > 3.0) for S_Z at 2p21 and 21q11 and S_WID at Xq25-q26. Inclusion of height and BMI as covariates resulted in much lower LOD scores for S_Z, whereas linkage signals for S_Z at 4q25, S_CSA at 4q32 and S_CSA and S_Z at 15q21 increased after the adjustment. Linkage of FNL at 1q and 13q, NSA at 2q and NN_WID at 16q did not change after the adjustment. Conclusion: Suggestive linkages of bone geometric indices were found at 1q, 2p, 4q, 13q, 15q and Xq. The identification of significant linkage regions after adjustment for BMI and height may point to QTLs influencing femoral bone geometry independent of body size.

AB - Introduction: Femoral geometry contributes to bone strength and predicts hip fracture risk. The purpose of this study was to evaluate heritability (h2) of geometric indices of the proximal hip and to perform whole-genome linkage analyses of these traits, adjusted for body size. Methods: DXA scans of the proximal femur from 1473 members of 323 pedigrees (age range 31-96 years) from the population-based Framingham Osteoporosis Study were obtained. Using the hip structural analysis program, we measured femoral neck length (FNL, cm) and neck-shaft angle (NSA); subperiosteal width (WID, cm), cross-sectional area (CSA, cm2); and section modulus (Z, cm3) at the narrowest section of the neck (NN), intertrochanteric (IT) and femoral shaft (S) regions. Linkage analyses were performed for the above indices with a set of 636 markers using variance components maximum likelihood method. Results: Substantial genetic influences were found for all geometric phenotypes, with h2 values between 0.28 (NSA) and 0.70 (IT_WID). Adjustment for height and BMI did not alter h2 of NSA and FNL but decreased h2 of the cross-sectional indices. We obtained substantial linkage (multipoint LOD > 3.0) for S_Z at 2p21 and 21q11 and S_WID at Xq25-q26. Inclusion of height and BMI as covariates resulted in much lower LOD scores for S_Z, whereas linkage signals for S_Z at 4q25, S_CSA at 4q32 and S_CSA and S_Z at 15q21 increased after the adjustment. Linkage of FNL at 1q and 13q, NSA at 2q and NN_WID at 16q did not change after the adjustment. Conclusion: Suggestive linkages of bone geometric indices were found at 1q, 2p, 4q, 13q, 15q and Xq. The identification of significant linkage regions after adjustment for BMI and height may point to QTLs influencing femoral bone geometry independent of body size.

KW - Body size and body composition

KW - Geometry

KW - Heritability

KW - Proximal femur

KW - Quantitative trait loci

KW - Whole-genome linkage

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Proximal hip geometry is linked to several chromosomal regions: Genome-wide linkage results from the Framingham Osteoporosis Study

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

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