Faculty Collaboration Database

Mapping quantitative trait loci for cross-sectional geometry at the femoral neck. J Bone Miner Res 2005 Nov;20(11):1973-82

Date

10/20/2005

Pubmed ID

16234971

DOI

10.1359/JBMR.050715

Scopus ID

2-s2.0-27444437567 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

UNLABELLED: A genome-wide linkage scan was performed in a sample of 79 multiplex pedigrees to identify genomic regions linked to femoral neck cross-sectional geometry. Potential quantitative trait loci were detected at several genomic regions, such as 10q26, 20p12-q12, and chromosome X.

INTRODUCTION: Bone geometry is an important determinant of bone strength and osteoporotic fractures. Previous studies have shown that femoral neck cross-sectional geometric variables are under genetic controls. To identify genetic loci underlying variation in femoral neck cross-sectional geometry, we conducted a whole genome linkage scan for four femoral neck cross-sectional geometric variables in 79 multiplex white pedigrees.

MATERIALS AND METHODS: A total of 1816 subjects from 79 pedigrees were genotyped with 451 microsatellite markers across the human genome. We performed linkage analyses on the entire data, as well as on men and women separately.

RESULTS: Significant linkage evidence was identified at 10q26 for buckling ratio (LOD = 3.27) and Xp11 (LOD = 3.45) for cortical thickness. Chromosome region 20p12-q12 showed suggestive linkage with cross-sectional area (LOD = 2.33), cortical thickness (LOD = 2.09), and buckling ratio (LOD = 1.94). Sex-specific linkage analyses further supported the importance of 20p12-q12 for cortical thickness (LOD = 2.74 in females and LOD = 1.88 in males) and buckling ratio (LOD = 5.00 in females and LOD = 3.18 in males).

CONCLUSIONS: This study is the first genome-wide linkage scan searching for quantitative trait loci underlying femoral neck cross-sectional geometry in humans. The identification of the genes responsible for bone geometric variation will improve our knowledge of bone strength and aid in development of diagnostic approaches and interventions for osteoporotic fractures.

Author List

Shen H, Long JR, Xiong DH, Liu YJ, Liu YZ, Xiao P, Zhao LJ, Dvornyk V, Zhang YY, Rocha-Sanchez S, Liu PY, Li JL, Deng HW

MESH terms used to index this publication - Major topics in bold

Absorptiometry, Photon
Adult
Age Factors
Aged
Aged, 80 and over
Bone Density
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 20
Chromosomes, Human, X
Female
Femur Neck
Genetic Linkage
Genome, Human
Humans
Lod Score
Male
Microsatellite Repeats
Middle Aged
Pedigree
Principal Component Analysis
Quantitative Trait Loci
Sex Factors