GENETIC LINKAGE TO LOW PEAK BONE MASS

Project: Research project

Project Details

Description

Low trauma fractures are a major public health problem in the
elderly. The most powerful, measurable determinant of fracture
risk is low bone mass and the most important determinant of late
life bone mass is peak bone mass (PBM). The heritability of PBM
is high, estimates ranging from 50-88 percent. Both association
studies with candidate genes and linkage studies with dense
genetic markers covering the whole human genome have merit in
searching for genes underlying variation in PBM.

We will conduct both types of studies to: 1) identify genomic
regions (-5cM in length) responsible for -15 percent or more of
variation in PBM; 2) test whether the vitamin D receptor (VDR)
genomic region is responsible for -15 percent or more of the
variation in PBM using linkage studies; 3) test whether genomic
regions containing 29 candidate genes underlie variation in PBM
using an association study approach. We will obtain 212 full sib
pairs extremely discordant for PBM (EDSP) and 866 full sib pairs
extremely concordant for low PBM (ECSP). All sib pairs and their
parents (1803 individuals) will be genotyped at 361 highly
polymorphic microsatellite markers about evenly spaced across the
human genome using an automated fluorescence based genotyping
system. Additionally, we will genotype 29 candidate genes.

Identifying genetic loci underlying PBM variation is the first
step in unraveling the major genetic cause of low bone mass, the
main measurable phenotype associated with osteoporosis. It will
expedite the characterization of mutations and their functional
products responsible for low PLB, and also help later studies of
the interaction of genetic and environmental causes of low PBM.
This knowledge is essential for development of preventive
interventions and/or cures for osteoporosis that can be based on
individuals' specific genotypes.
StatusFinished
Effective start/end date9/30/978/31/02

Funding

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $187,732.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases

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