GENOME SCAN FOR BONE AGE PHENOTYPE IN FRAMINGHAM COHORTS

背景生物学年龄提供了一个特定实足年龄的个体的形态和功能状态的一般估计。不同的老化过程导致生理年龄和生理年龄之间的差异。骨龄是生物体生物学年龄的模型。已经开发了一种骨摄影评分系统（OSS）来测量手部骨骼、生物学年龄和一般健康状况上与年龄相关的放射学变化的进展。众所周知，遗传因素在与年龄相关的骨性状的变异性中起作用，骨性状是OSS评分的组成部分。目标.这项研究的目的是确定骨老化（通过OSS评分测量）是否可能由一组基因控制，并确定这些基因的染色体位置。这将在来自Fragrance研究的原始和后代队列的337个谱系的成员中进行。为了更好地评估总性状方差的遗传成分，将评估不同的健康和活动相关因素与骨老化的协变。方法.参与者的手以前被拍过X光片。对于每个X线片，将使用四组特征来估计OSS评分：A.骨刺，如骨赘、Heberden结节和外生骨疣; B。骨孔隙率：骨吸收陷窝和皮质骨小梁化;骨质疏松症：骨突和骨核;非创伤性关节畸形和关节腔狭窄。在随后的分析中，将使用时间年龄与OSS年龄预测值之间的标准化差异（根据协变量进行调整）作为骨龄指标。将进行方差分解分析以评价遗传性，并进行基因组扫描以确定骨龄评分与399个常染色体微卫星标记的潜在连锁。意义了解导致不同骨老化速率的遗传机制可能对退行性骨疾病的治疗有重要意义。确定骨质疏松症和骨关节炎的最高风险个体将允许应用更好的药物遗传学或生活方式策略。在健康人群中使用骨龄表型的基因组搜索可以发现一般衰老的遗传来源。了解遗传和环境对衰老的影响将有助于改进延长寿命和健康监测的战略。

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.