GENOME SCAN FOR BONE AGE PHENOTYPE IN FRAMINGHAM COHORTS

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BACKGROUND. Biological age provides a general estimate of the morphological and functional status of an individual at a particular chronological age. Different individual rates of the aging process lead to disparities between chronological and biological age. Bone age serves as a model of biological age of an organism. An osteographic scoring system (OSS) has been developed to measure progression of age-related radiographic changes on hand bones, biological age, and general health status. It is well known that genetic factors play a role in variability of age-related bone traits, components of OSS score. OBJECTIVES. The aim of the proposed study is to determine whether bone aging, as measured by OSS score, may be governed by a set of genes, and to determine the chromosomal location of these genes. This will be done in members of 337 pedigrees from the Original and Offspring Cohorts of Framingham Study. To better assess the genetic component of total trait variance, different health- and activity-related factors will be evaluated for covariation with bone aging. METHODS. Hands of participants were previously radiographed. For each roentgenogram OSS score will be estimated, using four groups of features: A. Bony spurs, such as osteophytes, Heberden nodes, and exostoses; B. Bone porosity: resorption lacunae and trabecularization of cortex; C. Osteosclerosis: enostosis and sclerotic nuclei; and D. Non-traumatic articular deformities and joint cavities narrowing. The standardized difference between the chronological and the predicted by OSS age, adjusted on covariates, will be used as a measure of bone age in subsequent analyses. Variance decomposition analysis will be done to evaluate heritability, and a genome scan will be performed to identify potential linkage of bone age score with 399 autosomal microsatellite markers. SIGNIFICANCE. Understanding of the genetic mechanisms leading to different rates of bone aging may significantly contribute to the treatment of degenerative bone disease. Identifying the highest risk individuals for osteoporosis and osteoarthritis will allow to apply better pharmacogenetic or life-style strategies. A genome search using a bone age phenotype in a healthy population may discover genetic sources of aging in general. Knowledge of genetic and environmental contributions to aging will help to improve strategies for increasing longevity and health monitoring.