GALA II

哮喘和肥胖是主要的公共卫生问题，对低收入和少数族裔儿童的影响不成比例。流行病学研究一直表明哮喘和肥胖之间存在联系。在所有美国人中，哮喘患病率在波多黎各人中最高，在墨西哥裔美国人中最低。这两个人群的肥胖率都很高。肥胖哮喘可能是哮喘的一种独特的表型，具有更困难的临床病程和对哮喘控制器治疗的反应改变。肥胖和哮喘的独立危险因素对低收入和少数族裔儿童的影响不成比例。共同的早期接触是已知的风险因素。共同的遗传风险因素也很重要，双胞胎研究表明，肥胖的遗传成分中有8%与哮喘有关。对低收入少数族裔儿童的全面研究将有助于揭示遗传学、社会人口学和早期生活事件对这一人群中哮喘和肥胖症共同发生的贡献。拉丁裔是一个理想的人群，可以梳理出与肥胖和哮喘相关的遗传、社会和环境风险因素。拉美裔是美国最大的少数族裔人口，也是所有美国儿童中最大的人口群体。拉美裔人在个人和群体层面上的基因祖先都有相当大的差异，这可以用来解开哮喘和肥胖症易感性之间的复杂联系。我们对哮喘和肥胖进行了美国最大的混合物图谱扫描。我们发现了三个与哮喘和肥胖症相关的混合物图谱峰值，表明在这些地区存在导致哮喘和肥胖的多效性风险变量。 拉美裔人口中的肥胖症。这个roposal的目标是通过混合图谱确定的候选区域的深度重新测序来识别与哮喘和肥胖症相关的新的遗传变异。我们还将测试遗传变异和基因表达水平之间的相关性，以确定与每种情况相关的假定表达数量性状基因座(EQTL)。最后，我们将在NHLBI赞助的Eve哮喘联盟的几个独立人群中测试已识别的eQTL。

Asthma and obesity are leading public health concerns that disproportionately affect low-income and minority children. Epidemiologic studies have consistently shown an association between asthma and obesity. Among all US populations, asthma prevalence is highest in Puerto Ricans and lowest in Mexican Americans. Obesity is high in both populations. Obese asthma may be a unique phenotype of asthma, with a more difficult clinical course and altered response to asthma controller therapy. Independent risk factors for both obesity and asthma disproportionately impact low income and minority children. Shared early-life exposures are known risk factors. Shared genetic risk factors are also important Twin studies indicated that 8% of the genetic component of obesity is shared with asthma. A comprehensive study of low income minority children will help to uncover the contributions of genetics, socio-demographic, and early-life events to the co-occurrence of asthma and obesity in this population. Latinos are an ideal population to tease apart the genetic, social and environmental risk factors associated with obesity and asthma. Latinos are the largest minority population in the United States and the largest demographic group among all U.S. children. Latinos are admixed with considerable variation in genetic ancestry, both at the individual and group levels, and this can be leveraged to untangle complex associations between asthma and obesity susceptibility. We performed the largest admixture mapping scan of asthma and obesity in the U.S. We identified three admixture mapping peaks that were associated with both asthma and obesity, suggesting there are pleiotropic risk variants in these regions that contribute to both asthma and obesity in Latino populations. The goal of this roposal is to identify novel genetic variants associated with both asthma and obesity by deep resequencing of candidate regions identified through admixture mapping. We will also test for correlations between the genetic variation and levels of gene expression to identify putative expression quantitative trait loci (eQTLs) that are associated with each condition. Finally, we will test identified eQTLs in several independent populations from the NHLBI sponsored EVE asthma consortium.