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许多基因造成的，每个基因都具有低至中等人群频率的多种易患疾病的等位基因。该项目的总体目标是鉴定基因中的一个或多个变异，这些变异负责西班牙裔儿童中 13q 染色体上的空腹血糖连锁信号和 1p 染色体上的空腹血清胰岛素、生长素释放肽和 IGFBP-1 的连锁信号。通过使用大规模 SNP 分型、详尽的 DNA 重测序和统计功能基因组学。该项目的具体目标是： 具体目标 1：确定导致西班牙裔儿童空腹血糖 13q 染色体上统计显着性（LOD=4.6）数量性状位点（QTL）的遗传变异。一个。为了根据关联分析对基因进行优先级排序，将在 1030 名儿童中对 13q 染色体 5 MB 区域中约 2200 个 SNP 的定制密集组进行基因分型。 b.为了确定对 13q 染色体上的重要 QTL 负责的遗传变异，将在 376 名儿童中对通过关联分析优先排序的基因（约四个基因）进行广泛的重新测序。 c.为了确定整个 VIVA LA FAMILIA 队列中的频率分布，将对剩余儿童 (n=654) 中识别出的变异进行基因分型。 d.为了统计识别影响西班牙裔儿童空腹血糖的潜在功能性遗传变异，将进行贝叶斯数量性状核苷酸（BQTN）分析。 e.为了在独立队列中复制潜在的功能性遗传变异，我们将对西班牙裔儿童 (SAFARI) 和西班牙裔成人 (SAFHS) 队列中的 SNP 进行基因分型和分析。具体目标 2：确定西班牙裔儿童空腹血清胰岛素、生长素释放肽和 IGFBP-1 染色体 1p 上具有统计学显着性 (LOD=3.2-3.4) QTL 的遗传变异。一个。为了根据关联分析对基因进行优先级排序，将在 1030 名儿童中对 1p 染色体 9 MB 区域中约 5200 个 SNP 的定制密集组进行基因分型。 b.为了识别导致 1p 染色体上显着 QTL 的遗传变异，将对 376 名儿童进行关联分析优先排序的基因（约 12 个基因）进行广泛的重新测序。 c.为了确定整个 VIVA LA FAMILIA 队列中的频率分布，将对剩余儿童 (n=654) 中识别出的变异进行基因分型。 d.为了统计确定影响西班牙裔儿童空腹血清胰岛素、生长素释放肽和 IGFBP-1 的潜在功能性遗传变异，将进行 BQTN 分析。 e.为了在独立队列中复制潜在的功能性遗传变异，我们将对西班牙裔儿童 (SAFARI) 和西班牙裔成人 (SAFHS) 队列中的 SNP 进行基因分型和分析。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，但导致这种易感性增加的遗传变异尚未确定。在这个项目中，我们建议鉴定影响西班牙裔儿童空腹血糖、胰岛素、生长素释放肽和 IGFBP1 的基因变异。影响儿童肥胖和 2 型糖尿病的基因的鉴定将促进儿童肥胖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