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 journalArticle

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 languageEnglish (US)
Pages (from-to)743-750
Number of pages8
JournalBone
Volume40
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint

Osteoporosis
Hip
Neck
Genome
Thigh
Body Size
Bone and Bones
Femur Neck
Photon Absorptiometry
Hip Fractures
Pedigree
Femur
Phenotype
Population

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Proximal hip geometry is linked to several chromosomal regions : Genome-wide linkage results from the Framingham Osteoporosis Study. / Demissie, S.; Dupuis, J.; Cupples, L. A.; Beck, T. J.; Kiel, D. P.; Karasik, D.

In: Bone, Vol. 40, No. 3, 03.2007, p. 743-750.

Research output: Contribution to journalArticle

Demissie, S. ; Dupuis, J. ; Cupples, L. A. ; Beck, T. J. ; Kiel, D. P. ; Karasik, D. / Proximal hip geometry is linked to several chromosomal regions : Genome-wide linkage results from the Framingham Osteoporosis Study. In: Bone. 2007 ; Vol. 40, No. 3. pp. 743-750.
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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.

PY - 2007/3

Y1 - 2007/3

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.

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