GENETIC EPIDEMIOLOGY OF CHILDHOOD SKELETAL MATURATION

这项拟议研究的最终目标是：1)表征基因 参与整个儿童期的骨骼成熟，2)定位和 确定尚不清楚的影响基因的重要性 儿童时期骨骼成熟的个体差异，以及3) 评估候选基因中的多态对 儿童时期骨骼成熟的个体差异。 而对儿童成长模式和性发育的研究 一直是许多研究的焦点，目前对此知之甚少 与骨骼成熟有关的过程。情况尤其如此。 关于儿童骨骼成熟的遗传学。 在这一建议中，骨骼成熟不同于骨骼 生长，指的是一组特定的射线照片 骨骼特征的明显变化在成人骨骼状态中达到顶峰 在年轻的成年期。骨骼成熟度是指一个人达到的状态 给出了童年时的实际年龄。骨骼成熟度是量化的 作为骨骼年龄，指定给骨骼或骨骼区域的值，即 以年和月表示的成熟度，而不考虑 孩子的实际年龄或实际年龄。 骨骼年龄反映了不同发育阶段的不同机制 和发展。在儿童早期，它在很大程度上是衡量 骨骼骨化开始的时间。在童年中期，它主要是 衡量骨骼形状变化的指标，既有个体的，也有尊重的 形成联合队形。在生长发育接近尾声时， 青春期，骨龄在很大程度上是衡量骨痂程度的指标。 核聚变。 在拟议的研究中，骨骼年龄是根据系列X光照片进行评估的 作为FELS的一部分收集的手腕和膝盖 纵向研究。有超过15,500个骨骼年龄评估来自 从1930年到现在拍摄的手腕X光片，以及大约7750张 从1931年至1931年间拍摄的膝关节X线片对骨骼年龄的评估 1987年，900多名儿童参加了一次或另一次 FELS纵向研究，从婴儿期到 至少18年。这些人总共代表了213个核 以及大家庭，其中大多数家庭成员的DNA来自 已经被收集，或目前正在被收集，作为 包括先前和正在进行的研究。这些数据提供了一个完整的 史无前例的、彻底的阐明基因的独特机会 儿童时期骨骼成熟的结构。

The ultimate goals of the proposed study are to: 1) characterize genetic involvement in skeletal maturation throughout childhood, 2) locate and determine the significance of as yet unknown genes influencing individual variation in skeletal maturation during childhood, and 3) evaluate the contributions of polymorphisms in candidate genes to individual variation in skeletal maturation during childhood. While the study of childhood growth patterns and sexual development has been the focus of much study, very little is presently known about processes involved in skeletal maturation. This is especially so regarding the genetics of childhood skeletal maturation. In this proposal, skeletal maturation, as distinguished from skeletal growth, refers to the process whereby sets of specific radiographically visible changes in skeletal features culminate in adult skeletal status in young adulthood. Skeletal maturity refers to status achieved by a given chronological age in childhood. Skeletal maturity is quantified as skeletal age, a value assigned to a bone or skeletal area that is the level of maturity expressed in years and months irrespective of the child's actual or chronological age. Skeletal age reflects different mechanisms at different stages of growth and development. During early childhood, it is largely a measure of the timing of ossification onset in bones. In mid-childhood, it is largely a measure of changes in bone shape, both individually and with respect to joint formation. Near the end of growth and development, during puberty, skeletal age is largely a measure of degree of epiphyseal fusion. Skeletal age is assessed in the proposed study from serial radiographs of the hand-wrist and the knee collected as part of the Fels Longitudinal Study. There are over 15,500 skeletal age assessments from hand-wrist radiographs taken from 1930 to the present, and some 7,750 assessments of skeletal age from knee radiographs taken between 1931 and 1987, of over 900 children participating at one time or another in the Fels Longitudinal Study who have been studied serially from infancy to at least 18 years. These individuals represent a total of 213 nuclear and extended families, most of which have family members from whom DNA has already been collected, or is presently being collected, as part of both previous and ongoing studies. These data offer an altogether unprecedented and thoroughly unique opportunity to elucidate the genetic architecture of skeletal maturation during childhood.