Whole-exome Sequencing to Identify Genetic Variants Associated With Severe Childhood Obesity, and Tracking the Changing Prevalence of Obesity Related Complications
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 800
- 试验地点
- 2
- 主要终点
- Identify novel obesity genes and variants using whole-exome sequencing (WES) in our local Singaporean obese children.
研究概览
简要总结
Obesity is a complex multifactorial disease where genetics play an important role in predisposing children to early onset obesity. Though many obesity susceptible genes and variants have been identified with obesity, the most common obesity gene, MC4R only accounts for 5% of all early onset obesity cases. This implies that there may be more obesity related genes and variants that need to be unravelled to further delineate the relationship between obesity and genetics. The investigators propose in screening the exonic regions of all the genes in obese subjects using whole-exome sequencing (WES) to discover novel obesity related variants and genes.
Primary hypothesis The investigators hypothesized that our paediatric subjects with early-onset severe obesity will have strong genetic predisposition and therefore the cohort would be enriched with obesity susceptibility genetic variants.
Secondary hypothesis The investigators hypothesized that there is increasing prevalence of, and possibly worsening, obesity-related complications (namely glucose intolerance, hypertension, metabolic syndrome, non-alcoholic fatty liver disease) in our severely obese children, as compared to 15 years ago, due to an increasingly obesogenic environment promoting unhealthy lifestyle and eating habits.
详细描述
Number of subjects to be enrolled:
As our study aims to identify susceptible genetic variants associated with early onset obesity, we will be recruiting 400 obese children to participate in this genetic study, in addition to the existing DNA samples we collected in a previous study (DSRB Ref C/00/501). These 400 obese children will be recruited through NUH paediatric clinic and School Health Clinic at Health Promotion Board. We will also recruit family members of the obese children who are interested to join the research study. We will be using the DNA samples and information of 250 obese children previously recruited to the Obesity Genetic Study from January 2000 to December 2004 (DSRB Ref C/00/501). We will also be performing WES on 500 lean adults (as controls) recruited for an ongoing study titled "Whole exome sequencing to identify genes for extreme Myopia in Asian populations" (NUS-IRB reference code: 12-466).
Total number of new obese children subjects to be recruited: 400 Total number of family members (Parents and siblings): 500 Total number of existing obese children subjects to be used: 250 Total number of existing lean adult controls to be used: 500
Criteria for Recruitment:
The doctor will ask a few simple questions regarding the age and medical history of subjects.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion Criteria
- •The obese subject must meet all of the following inclusion criteria to participate in this study:
- •Ideal body weight for height (WFH) of at least 140% or BMI for age above 97th percentile
- •Overweight before 10 years of age
- •Informed consent from both obese children subject and legal representative e.g. parents
- •Family member must meet all of the following inclusion criteria to participate in this study:
- •Must be parent or direct sibling of obese subject
- •Informed consent from both subject and parent is subject is below 21 years of age
排除标准
- •All subjects meeting any of the exclusion criteria at baseline will be excluded from participation:
- •Unfit for blood testing and OGTT testing
- •No informed consent
结局指标
主要结局
Identify novel obesity genes and variants using whole-exome sequencing (WES) in our local Singaporean obese children.
时间窗: 3 years
whole exom sequencing data
次要结局
- Assess and compare the metabolic phenotype of the current severely obese children and severely obese children recruited in a similar fashion 15 years ago by the obesity gene study (OGS) group.(3 years)
- Stool microbiota/metagenomics in obese children, and metabolic health(3 years)
- Biomarkers, inflammatory markers and PBMC gene expressions between metabolically healthy obese and metabolically unhealthy obese(3 years)
研究者
Lee Yung Seng
Professor
National University of Singapore