Genetics of Birth Weight in Mexican Americans

墨西哥裔美国人出生体重的遗传学

• 批准号: 6536421
• 负责人: RAVINDRANATH DUGGIRALA
• 金额: $ 40.69万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-10 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6536421
• 关键词: Mexican Americans; clinical research; data collection; disease /disorder proneness /risk; family genetics; gene environment interaction; genetic markers; genetic susceptibility; genome; genotype; human birth weight; human subject; hypertension; insulin sensitivity /resistance; linkage mapping; low birth weight infant human; metabolic syndrome; metabolism disorder; noninsulin dependent diabetes mellitus; obesity; phenotype; quantitative trait loci; telecommunications

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.

大量流行病学研究表明，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，那么尝试了解其病因以及其与成年疾病相关的模式将至关重要，特别是对于墨西哥裔美国人等人群，这些人群容易患上肥胖、2 型糖尿病和代谢综合征等疾病。 关于出生体重变异的遗传基础的知识非常有限。 此外，人们对于出生体重与成年疾病之间是否存在共同的遗传决定因素也知之甚少。该项目的目的是开展遗传流行病学调查，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和统计遗传技术，以检查目前正在接受治疗的210个墨西哥裔美国家庭出生体重变异的遗传基础。与肥胖、2型糖尿病和高血压等多种疾病的基因决定相关的研究。具体来说，本研究旨在利用方差分量连锁技术绘制出生体重的易感基因图谱。 我们提案的主要目标是： 1）除了我们已经收集的 602 个人的出生体重数据之外，还收集约 700 个人的出生体重数据； 2）利用多点连锁方法确定出生体重的潜在易感位点； 3) 通过在每个感兴趣区域中键入附加标记并使用多点连锁分析来进一步探索感兴趣区域； 4) 考察这些易感位点是否对成人疾病和代谢紊乱具有多效性影响； 5) 确定影响出生体重的多个基因座并检查影响出生体重的基因的相互作用效应。我们将使用约 800 名个体（110 个家庭）的出生体重数据，并获得 10cM 基因组扫描图谱，进行多点连锁分析，以确定出生体重的易感位点。 在检测到潜在的连锁信号后，我们将使用来自约 1300 名个体的数据，对每个区域 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基因座是否对成年期疾病（如肥胖、2 型疾病、高血压和代谢综合征）有任何共同的遗传影响（即多效性）。 鉴于我们已经在基因组中定位了影响 2 型糖尿病、肥胖、胰岛素抵抗和血脂等特征的各种基因座，本研究将提供一个独特的机会来识别对出生体重和代谢疾病具有共同遗传影响的基因。成年期。