COLLABORATIVE PERINATAL PROJECT IN OBESITY GENOME-WIDE ASSOCIATION STUDIES

肥胖全基因组关联研究围产期合作项目

• 批准号: 10670539
• 负责人: MICHAEL TSAI
• 金额: $ 219.44万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10670539
• 关键词: 7 year old; Address; Adult; African; African American; Age; Aliquot; American; Bar Codes; Birth; Body mass index; Cardiometabolic Disease; Child; Childhood; Complex; Contractor; DNA; Enrollment; Environment; Etiology; European; Food Energy; Genetic; Genetic Predisposition to Disease; Genotype; Growth; Heritability; Life Style; Medical center; Monitor; Neonatal; Obesity; Obesity Epidemic; Pattern; Perinatal; Phenotype; Population; Pregnancy; Prenatal care; Procedures; Sampling; Serum; Ships; Standardization; Time; Umbilical Cord Blood; United States; Vial device; Woman; cohort; early childhood; early pregnancy; expectation; food consumption; genome wide association study; genomic locus; improved; infancy; lifestyle factors; milliliter; novel; obesity in children; obesogenic; offspring; physical inactivity; prevent; prospective; whole genome

Obesity is a complex multi-factorial condition that results from genetic predisposition and lifestyle factors such as high energy food consumption and physical inactivity. The heritability of childhood BMI has been estimated to be 40-70%. The high heritability of obesity in the context of the current obesogenic environment strongly suggests that genetic factors are implicated in population patterns of obesity and, are essential to consider in population approaches to address the obesity epidemic. Identifying genetic factors that influence early childhood BMI can inform the etiology of obesity as well as help to identify strategies to prevent and treat childhood obesity and related adult cardiometabolic diseases. Currently, the genetic factors that influence early childhood BMI are not well understood. Genome-wide association studies (GWAS) could help identify these genetic factors and distinguish their effects across ages. The Collaborative Perinatal Project (CPP) was a prospective pregnancy cohort that enrolled women who had prenatal care at 12 medical centers in the United States from 1959-1965. Women were followed from early pregnancy onwards and their offspring were monitored from birth through 7 years of age. While the CPP enrolled children prior to the obesity epidemic and obesogenic lifestyle in the United States, any potential interactions between genetic factors discovered using this cohort and recent environmental modifiers can be validated using other more recent cohorts. The CPP offers opportunities to discover novel genetic loci related to obesity among Africans and Europeans and to improve the functional characterization of known loci discovered in European populations. The primary aims of this study are to identify genetic influences on growth and obesityrelated phenotypes during neonatal, infancy and early childhood periods among children in the CPP cohort (n= 10200; 5100 African American and 5100 European American), and to identify trans-ancestral and ancestry-specific genetic loci associated with BMI at 7 time points from birth to 7 years of age (birth, 4 months, 8 months, 12 months, 3 years, 4 years, 7 years) via trans-ancestry GWAS. The feasibility of this project was determined in a previous pilot Task Order. The Contractor shall receive the samples over a period of approximately 8 months, with the first shipment of samples providing ample material to confirm the pilot results and standardize procedures. Samples shall arrive in their original vials, with an expectation of approximately 1 milliliter of volume per sample. The Contractor shall aliquot the volume needed for the DNA extraction and transfer any remaining volume into a new, barcoded

肥胖症是一种复杂的多因素疾病，由遗传易感性和生活方式因素如高能量食物消耗和身体活动不足引起。儿童BMI的遗传率估计为40- 70%。在当前致肥胖环境的背景下，肥胖的高遗传性强烈表明遗传因素与肥胖的人群模式有关，并且在解决肥胖流行病的人群方法中必须考虑遗传因素。 确定影响儿童早期BMI的遗传因素可以为肥胖的病因提供信息，并有助于确定预防和治疗儿童肥胖和相关成人心脏代谢疾病的策略。目前，影响儿童早期BMI的遗传因素还不清楚。全基因组关联研究（GWAS）可以帮助识别这些遗传因素，并区分它们在不同年龄段的影响。 围产期合作项目（CPP）是一项前瞻性妊娠队列研究，招募了1959-1965年在美国12个医疗中心接受产前护理的妇女。从怀孕早期开始对妇女进行跟踪，并从出生到7岁对她们的后代进行监测。虽然CPP在美国肥胖流行和致肥胖生活方式之前招募儿童，但任何潜在的相互作用 使用该群组发现的遗传因素与最近的环境修饰物之间的关系可以使用其他更近的群组来验证。CPP提供了发现与非洲人和欧洲人肥胖相关的新遗传基因座的机会，并改善了欧洲人群中发现的已知基因座的功能特征。 本研究的主要目的是确定CPP队列中新生儿、婴儿期和儿童早期生长和肥胖相关表型的遗传影响（n= 10200; 5100名非洲裔美国人和5100名欧洲裔美国人），并在从出生到7岁的7个时间点鉴定与BMI相关的跨祖先和祖先特异性遗传基因座（出生，4个月，8个月，12个月，3岁，4岁，7岁）通过跨祖先GWAS。 该项目的可行性已在先前的试点任务指令中确定。承包商应在大约8个月的时间内收到样品，第一批样品提供了充足的材料，以确认试验结果和标准化程序。样品应装在原始小瓶中，预计每份样品的体积约为1毫升。承包商应等分DNA提取所需的体积，并将任何剩余体积转移到新的条形码