Genetics of Birth Weight in Mexican Americans

许多流行病学研究表明，低出生体重与成年后的疾病有关，包括2型糖尿病、肥胖、心血管疾病和代谢综合征。 如果是这样的话，试图了解其病因以及其与成年期疾病相关的模式将是至关重要的，特别是在墨西哥裔美国人等人群中，这些人群容易患肥胖症，2型糖尿病和代谢综合征等疾病。 关于出生体重变化的遗传基础的知识非常有限。 此外，关于出生体重和成年后疾病之间的联系是否有任何共同的遗传决定因素，人们知之甚少。该项目的目的是进行遗传流行病学调查，涉及分子遗传数据，出生体重数据及其相关的成人表型数据，以及统计遗传技术，以检查210个墨西哥裔美国家庭出生体重变异的遗传基础，这些家庭目前正在调查与肥胖，2型糖尿病和高血压等各种疾病的遗传决定有关的疾病。具体而言，使用方差分量连锁技术，本研究的目的是映射易感基因的出生体重。 我们建议的主要目的是：1）除已收集的602名出生体重数据外，再收集约700名出生体重数据; 2）利用多点连锁方法确定出生体重的潜在易感基因位点; 3）通过在每个感兴趣的区域中键入额外的标记并利用多点连锁分析，进一步探索感兴趣的区域; 4）检测这些易感基因座是否对成人疾病和代谢紊乱有任何多效性影响; 5）鉴定影响出生体重的多个基因座，并检测影响出生体重的基因的干扰效应。我们将使用来自约800个个体（110个家庭）的出生体重数据，在这些个体上可获得10 cM的基因组扫描图，我们将进行多点连锁分析，以确定出生体重的易感基因座。 在检测到潜在的连锁信号后，我们将使用来自约1300个个体的数据，每个区域使用10个标记进行额外的基因分型，以使用多点方法精确定位出生体重的易感基因。 我们还将检查出生体重的基因座是否有任何共同的遗传影响（即，多效性）对成年期疾病如肥胖症、2型疾病、高血压和代谢综合征的作用。 鉴于我们已经定位了基因组中影响2型糖尿病，肥胖，胰岛素抵抗和脂质等性状的各种基因座，本研究将提供一个独特的机会来识别对出生体重和成年代谢疾病具有共同遗传影响的基因。

Numerous epidemiological studies have shown that low birth weight is associated with diseases in adult life including type 2 diabetes, obesity, cardiovascular disease and the Metabolic Syndrome. If so, attempts to understand its etiology as well as the patterns underlying its association with diseases in adulthood would be of utmost importance especially in populations such as the Mexican Americans, which are prone to diseases such as obesity, type 2 diabetes and the Metabolic Syndrome. Knowledge about the genetic basis of variation in birth weight is very limited. Also, little is known about whether associations between birth weight and diseases in adult life have any common genetic determinants. The purpose of this project is to conduct a genetic epidemiologic investigation involving molecular genetic data, birth weight data and its related adult phenotypic data, and statistical genetic techniques to examine the genetic basis of variation in birth weight in 210 Mexican American families that are currently under investigation in relation to the genetic determination of various diseases including obesity, type 2 diabetes, and hypertension. Specifically, using variance-components linkage techniques, this study aims to map susceptibility genes for birth weight. The main objectives of our proposal are: 1) to collect birth weight data for about 700 individuals in addition to the birth weight data we have already collected for 602 individuals; 2) to identify potential susceptibility loci for birth weight using multipoint linkage approach; 3) to further explore the regions of interest by typing additional markers in each region of interest and using multipoint linkage analysis; 4) to examine whether these susceptibility loci have any pleiotropic influences on adult diseases and metabolic disorders; and 5) to identify multiple loci affecting birth weight and to examine interactional effects of genes influencing birth weight. Using birth weight data from about 800 individuals (110 families) on whom a 10cM genome scan map is available, we will conduct a multi-point linkage analysis to identify susceptibility loci for birth weight. After detecting potential signals for linkage, we will perform additional genotyping with 10 markers per region using data from about 1300 individuals to precisely localize the susceptibility genes for birth weight using the multipoint approach. We will also examine whether the loci for birth weight have any common genetic influences(i.e., pleitropy) on diseases in adulthood such as obesity, type 2 diseases, hypertension, and the Metabolic Syndrome. Given that we have already localized various loci across the genome affecting such traits as type 2 diabetes, obesity, insulin resistance, and lipids, this present study will provide a unique opportunity to identify genes that have common genetic influences on birth weight and metabolic diseases in adulthood.