Obesity and Diabetes Familial Risk in Hispanic Children

西班牙裔儿童的肥胖和糖尿病家族风险

• 批准号: 8241965
• 负责人: NANCY F. BUTTE
• 金额: $ 56.61万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-15 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8241965
• 关键词: 13q; Adult; Alleles; Biomedical Research; Child; Child Nutrition; Chromosomes; Comorbidity; Custom; DNA Resequencing; Detection; Diabetes Mellitus; Disease; Enrollment; Fasting; Foundations; Frequencies; Genes; Genotype; Glucose; Goals; Hispanics; Human Genome; IGFBP1 gene; Insulin; Insulin-Like Growth-Factor Binding Protein 1; Measurable; Medicine; Non-Insulin-Dependent Diabetes Mellitus; Nucleotides; Nutritional Study; Obesity; Phenotype; Population; Predisposition; Quantitative Trait Loci; Research; Risk; Serum; Signal Transduction; United States; Variant; Youth; base; cohort; college; fasting glucose; functional genomics; genetic variant; genome sequencing; ghrelin; obesity in children; obesity risk; obesity treatment; public health relevance; trait

DESCRIPTION (provided by applicant): Familial risk for obesity and diabetes in Hispanic children is due to a number of genes, each with multiple disease-predisposing alleles of low to intermediate population frequency. The overall goal of this project is to identify one or more variants in gene(s) that is/are responsible for the linkage signals on chromosome13q for fasting serum glucose and on chromosome 1p for fasting serum insulin, ghrelin and IGFBP-1 in Hispanic children by use of large scale SNP typing, exhaustive DNA resequencing and statistical functional genomics. The specific aims of this project are: Specific Aim 1: To identify genetic variants responsible for the statistically significant (LOD=4.6) quantitative trait locus (QTL) on chromosome 13q for fasting serum glucose in Hispanic children. a. To prioritize genes based on association analysis, a custom, dense panel of ~2200 SNPs in a 5 MB region on chromosome 13q will be genotyped in 1030 children. b. To identify genetic variants responsible for the significant QTL on chromosome 13q, the genes prioritized by association analysis (~four genes) will be extensively resequenced in 376 children. c. To determine the frequency distribution in the entire VIVA LA FAMILIA cohort, the identified variants will be genotyped in the remaining children (n=654). d. To statistically identify potentially functional genetic variants influencing fasting serum glucose in Hispanic children, Bayesian quantitative trait nucleotide (BQTN) analyses will be performed. e. To replicate the potentially functional genetic variants in independent cohorts, we will genotype and analyze the SNPs' effects in cohorts of Hispanic children (SAFARI) and Hispanic adults (SAFHS). Specific Aim 2: To identify genetic variants responsible for the statistically significant (LOD=3.2-3.4) QTLs on chromosome 1p for fasting serum insulin, ghrelin and IGFBP-1 in Hispanic children. a. To prioritize genes based on association analysis, a custom, dense panel of ~5200 SNPs in a 9 MB region on chromosome 1p will be genotyped in 1030 children. b. To identify genetic variants responsible for the significant QTL on chromosome 1p, the genes prioritized by association analysis (~twelve genes) will be extensively resequenced in 376 children. c. To determine the frequency distribution in the entire VIVA LA FAMILIA cohort, the identified variants will be genotyped in the remaining children (n=654). d. To statistically identify potentially functional genetic variants influencing fasting serum insulin, ghrelin and IGFBP-1 in Hispanic children, BQTN analyses will be performed. e. To replicate the potentially functional genetic variants in independent cohorts, we will genotype and analyze the SNPs' effects in cohorts of Hispanic children (SAFARI) and Hispanic adults (SAFHS). PUBLIC HEALTH RELEVANCE: Hispanic youth in the United States are at increased risk for obesity and type 2 diabetes, and yet the genetic variants underlying this heightened susceptibility have not been identified. In this project, we propose to identify variants in genes that influence fasting glucose, insulin, ghrelin and IGFBP1 in Hispanic children. The identification of genes that influence childhood obesity and type 2 diabetes will advance the detection and treatment of obesity and its comorbidities in children.

描述（由申请人提供）：西班牙裔儿童肥胖和糖尿病的家族风险是由于许多基因引起的，每个基因都有多种疾病的等位基因低至中等人口频率。该项目的总体目标是确定基因中的一个或多个变体，该变体是/负责染色体13Q上的连锁信号，用于禁食血清葡萄糖和染色体1p，用于禁食血清胰岛素，生长素蛋白，生长素蛋白和IGFBP-1，在西班牙裔儿童中使用大型SNP SNP SNP型，耗尽的dna resistict and statipitions and Static staticity and Statitions and Statitions。该项目的具体目的是：具体目的1：确定负责统计学意义（LOD = 4.6）定量性状基因座（QTL）13Q上的遗传变异，用于西班牙裔儿童的禁食血清葡萄糖。一个。为了根据关联分析确定基因的优先级，在1030名儿童中，将对13Q染色体的5 MB区域中的惯例密集的面板约为2200个SNP。 b。为了鉴定负责在13q染色体上显着QTL的遗传变异，通过缔合分析（〜4个基因）优先考虑的基因将在376名儿童中进行广泛重新置于。 c。为了确定整个viva la familia队列中的频率分布，将在其余儿童中进行基因分型（n = 654）。 d。为了识别影响西班牙裔儿童空腹血糖的潜在功能遗传变异，将进行贝叶斯定量性状核苷酸（BQTN）分析。 e。为了复制独立队列中潜在的功能遗传变异，我们将基因型和分析SNP在西班牙裔儿童（Safari）和西班牙裔成年人（SAFHS）中的效应。具体目标2：确定在西班牙裔儿童中为禁食血清胰岛素，生长素蛋白和IGFBP-1的染色体1p上统计学意义（LOD = 3.2-3.4）的遗传变异。一个。为了根据关联分析确定基因的优先级，在1030名儿童中，将在9 MB区域的一个定制，密集的面板约为5200个SNP。 b。为了鉴定负责染色体1p染色体上显着QTL的遗传变异，通过缔合分析（〜22个基因）优先考虑的基因将在376名儿童中进行广泛重新置于。 c。为了确定整个viva la familia队列中的频率分布，将在其余儿童中进行基因分型（n = 654）。 d。为了识别影响空腹血清胰岛素，生长素蛋白和IGFBP-1在西班牙裔儿童中的潜在功能遗传变异，将进行BQTN分析。 e。为了复制独立队列中潜在的功能遗传变异，我们将基因型和分析SNP在西班牙裔儿童（Safari）和西班牙裔成年人（SAFHS）中的效应。公共卫生相关性：美国的西班牙裔青年患肥胖症和2型糖尿病的风险增加，但是尚未确定这种增强易感性的遗传变异。在这个项目中，我们建议在西班牙裔儿童中识别影响禁食葡萄糖，胰岛素，生长素蛋白和IGFBP1的基因的变体。影响儿童肥胖症和2型糖尿病的基因的鉴定将提高对儿童肥胖症及其合并症的检测和治疗。

项目成果

Predictors of Severe Obesity in Low-Income, Predominantly Hispanic/Latino Children: The Texas Childhood Obesity Research Demonstration Study.

• DOI: 10.5888/pcd14.170129
• 发表时间: 2017-12-28
• 期刊: Preventing chronic disease
• 影响因子: 5.5
• 作者: Salahuddin M;Pérez A;Ranjit N;Kelder SH;Barlow SE;Pont SJ;Butte NF;Hoelscher DM
• 通讯作者: Hoelscher DM