GENETIC EPIDEMIOLOGY OF CHILDHOOD OBESITY

儿童肥胖是成人肥胖和肥胖程度的预测指标。 体重(以体重与身高之比衡量) 成年人已被证明是发病率的一个重要预测因素，因为 以及动脉粥样硬化性心血管疾病的死亡率。我们 在爱荷华州马斯卡廷对1580人进行了一项家庭研究 284个家庭评估遗传对家庭的贡献 体重指数(BMI=kg/m2)水平的聚集性和发现 两个等位基因分离的证据(指定为L 较低和H代表较高BMI)在隐性基因座上解释35%， 而多基因座可以解释42%的BMI变异性 人口。我们估计其中37%的人 人群是H基因携带者，6%的人患有HH 基因分型。几种隐性肥胖的啮齿动物模型也有 已被鉴定，这些特征已被定位为啮齿动物 与人类上的区域同线的染色体区域 染色体1和7。这些结果表明，对人类的研究 导致观察到的体重指数变异性的基因是 现在是一次重要的冒险。在拟议的研究中，我们将重点放在 三个问题： 1)是否有人类基因或DNA序列具有可测量的 对肥胖量化指标的影响或对量化指标的影响 学龄儿童中与肥胖有关的特征 来自爱荷华州马斯卡廷 ？ 2)连锁基因座上的基因型别对 肥胖的数量指标和符合以下条件的数量性状 与来自马斯卡廷的核心家庭的肥胖有关？ 3)是否有证据表明体重指数与候选基因座存在关联 从兄弟姐妹对分析中鉴定出来的似乎是 分离H基因？ 这项研究将增加我们对遗传因素的理解 参与了肥胖的确定，并可能导致早期 确定有高风险的个人和家庭 与肥胖有关的慢性病。

Childhood obesity is predictive of adult obesity and the degree of ponderosity (as measured by body weight relative to height) in adults has been shown to be an important predictor of morbidity as well as mortality from atherosclerotic cardiovascular disease. We conducted a family study in Muscatine, Iowa of 1,580 individuals in 284 families to evaluate the genetic contribution to familial clustering of levels of the body mass index (BMI=kg/m2) and found evidence that the segregation of two alleles (designated as L for lower and H for higher BMI) at a recessive locus explains 35%, while polygenic loci explain 42% of the variability in BMI in this population. We estimate that 37% of the individuals in this population are carriers of the H gene and that 6% have the HH genotype. Several rodent models of recessive obesity have also been identified and the traits have been mapped to rodent chromosomal regions which are syntenic with regions on human chromosomes 1 and 7. These results suggest that a search for human genes that are responsible for the observed variability in BMI is now an important venture. In the proposed study, we will focus on three questions: 1) Are there human genes or DNA sequences which have measurable effects on quantitative indices of obesity or on quantitative traits that are associated with obesity among school-age siblings from Muscatine, Iowa ? 2) What effects do the genotypes at linked loci have on quantitative indices of obesity and on quantitative traits that are associated with obesity in nuclear families from Muscatine? 3) Is there evidence for linkage of BMI to candidate loci identified from the sib-pair analyses in families who appear to be segregating the H gene? This study should add to our understanding of the genetic factors involved in the determination of obesity and may lead to early identification of individuals and families at high risk for the chronic diseases that are associated with obesity.