GENETIC EPIDEMIOLOGY OF CHILDHOOD OBESITY

儿童肥胖是成年肥胖的预测指标， 体重（以体重与身高之比衡量） 成人已被证明是发病率的重要预测因素， 以及动脉粥样硬化性心血管疾病的死亡率。 我们 在爱荷华州的马斯卡廷进行了一项家庭研究， 284个家庭，以评估遗传贡献的家庭 体重指数（BMI=kg/m2）水平的聚类， 有证据表明，两个等位基因的分离（指定为L， 较低和H表示较高的BMI）在隐性基因座解释了35%， 而多基因位点解释了42%的BMI变异， 人口 我们估计，37%的人在这个 人群是H基因的携带者，6%的人有HH 基因型 一些隐性肥胖的啮齿动物模型也 这些特征已经被映射到啮齿动物身上 与人类染色体上的区域同线的染色体区域 染色体1和7。 这些结果表明，寻找人类 负责观察到的BMI变异的基因是 现在是一个重要的冒险。 在建议的研究中，我们会集中研究 三个问题： 1)是否有人类基因或DNA序列， 对肥胖定量指标的影响， 与学龄期兄弟姐妹肥胖相关的特征 来自爱荷华州的马斯卡廷 ? 2)连锁基因座的基因型对 肥胖的数量指标和数量性状， 与马斯卡廷核心家庭中的肥胖相关吗 3)是否有证据表明BMI与候选基因座有关联 从家庭中的同胞对分析中发现， 分离H基因 这项研究应该增加我们对遗传因素的理解 参与肥胖的确定，并可能导致早期 查明面临艾滋病毒/艾滋病高风险的个人和家庭 与肥胖有关的慢性疾病。

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.