Whole-exome Sequencing in Childhood Obesity

NCT02418377 | Completed

• 1 other identifier: NMRC/CIRG/1407/2014
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Childhood Obesity

Keywords

Obesity; Genetics; Whole exome sequencing; Children

Outcome Measures

Primary Outcomes (1)

• Identify novel obesity genes and variants using whole-exome sequencing (WES) in our local Singaporean obese children.

  whole exom sequencing data

  3 years

Secondary Outcomes (3)

• 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

• Biomarkers, inflammatory markers and PBMC gene expressions between metabolically healthy obese and metabolically unhealthy obese

  3 years

• Stool microbiota/metagenomics in obese children, and metabolic health

  3 years

Study Arms (2)

Obese children

The obese subject must meet all of the following inclusion criteria to participate in this study: 1. Ideal body weight for height (WFH) of at least 140% or BMI for age above 97th percentile 2. Overweight before 10 years of age 3. Informed consent from both obese children subject and legal representative e.g. parents

Family members of obese children

Family member must meet all of the following inclusion criteria to participate in this study: 1. Must be parent or direct sibling of obese subject 2. Informed consent from both subject and parent is subject is below 21 years of age

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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. 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 . We will also be performing WES on 500 lean adults (as controls) recruited for an ongoing study.

You may qualify if:

• 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
• Must be parent or direct sibling of obese subject
• Informed consent from both subject and parent is subject is below 21 years of age

You may not qualify if:

• Unfit for blood testing and OGTT testing
• No informed consent

Sponsors & Collaborators

• National University of Singapore: lead
• Health Promotion Board, Singapore: collaborator
• Genome Institute of Singapore: collaborator

Study Sites (2)

National University Hospital, Singapore

Singapore, 119074, Singapore

Location

Health Promotion Board

Singapore, 168937, Singapore

Location

Related Publications (3)

• Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, Shaffer T, Wong M, Bhattacharjee A, Eichler EE, Bamshad M, Nickerson DA, Shendure J. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009 Sep 10;461(7261):272-6. doi: 10.1038/nature08250. Epub 2009 Aug 16.

  PMID: 19684571 BACKGROUND

• Hinney A, Nguyen TT, Scherag A, Friedel S, Bronner G, Muller TD, Grallert H, Illig T, Wichmann HE, Rief W, Schafer H, Hebebrand J. Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS One. 2007 Dec 26;2(12):e1361. doi: 10.1371/journal.pone.0001361.

  PMID: 18159244 BACKGROUND

• Ramachandrappa S, Farooqi IS. Genetic approaches to understanding human obesity. J Clin Invest. 2011 Jun;121(6):2080-6. doi: 10.1172/JCI46044. Epub 2011 Jun 1.

  PMID: 21633175 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

15-19mls of blood will be extracted from each subject. Blood will be processed to obtain plasma/serum and DNA will be extracted from blood cells. Plasma/serum and DNA samples will be stored at -80degree Celsius.

MeSH Terms

Conditions

Pediatric Obesity; Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Yung Seng Lee, M.D, PhD

  National University Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 3 Weeks
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 12, 2015
• First Posted: April 16, 2015
• Study Start: August 10, 2015
• Primary Completion: February 10, 2019
• Study Completion: September 10, 2020
• Last Updated: September 16, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2)