Study to Investigate Genetic Causes of Severe Early Childhood Onset Obesity. (GECO)

Study to Identify Rare Genetic Variants Causing Severe Early Childhood Obesity

This study aims to investigate genetic causes of early childhood obesity.

The investigators will enroll children and young adults with severe early onset obesity (BMI > 99th percentile) diagnosed prior to 6 years of age. The investigators will ask questions about the health and eating behavior of the participants, and perform a brief physical examination. The investigators will collect saliva or blood to perform genetic testing from the participants and invite family members to enroll in the study.

Study Overview

• Status: Recruiting
• Conditions: Obesity

Detailed Description

This is a clinical and genomic study designed to investigate monogenic causes of severe early childhood obesity.

Participants with severe early onset obesity will be identified by screening of the clinical database or referred for the study. These subjects will be invited to participate in the study. After obtaining informed consent, the investigators will obtain history on the proband and the family, and perform a brief examination in addition to collecting genetic material.

Targeted sequencing of genes associated with monogenic and syndromic forms of obesity will be performed using next-generation sequencing. In selected individuals with favorable family history, exome or whole genome sequencing will be performed. Functional analysis of newly identified variants will be performed where possible.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Vidhu Thaker, M.D.; Phone Number: 212-851-5315; Email: vvt2114@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Contact: Vidhu Thaker, MD; Phone Number: 212-851-5315; Email: vvt2114@cumc.columbia.edu
    • New York, New York, United States, 10032-3822
      • Recruiting
      • Vidhu Thaker
      • Contact: Vidhu Thaker, M.D.; Phone Number: 212-851-5315; Email: vidhu.thaker@childrens.harvard.edu
      • Principal Investigator: Vidhu Thaker, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

This study will enroll children with BMI > 99th percentile for age noted prior to 6 years of age. Current age of the child can vary from 0-21 years.

Description

Inclusion Criteria:

- BMI > 99th percentile documented at age < 6 years of age

Exclusion Criteria:

• Known genetic causes of obesity
• Known Endocrine causes of obesity.
• Neurologic tumor, trauma or surgery
• Prior malignancy or transplant
• Known autoimmune diseases
• Edema of a known or unknown cause
• Prolonged steroid use.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Early-onset severe obesity; The study will enroll children and young adults up to 21 years of age with early onset severe obesity (BMI > 99th percentile noted at an age < 6 years of age).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of known or novel genetic variants in genes that underlie obesity.	Identification of known or novel genetic variants in genes that underlie obesity.	1.5-2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of melanocortin receptor 4 mutations.	We will test the hypothesis that 1-3% of early onset obesity could be explained by carriage of mutation of monogenic obesity such as melanocortin receptor 4 in a mixed pediatric population.	2 years

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Boston Children's Hospital
• Investigators: Principal Investigator: Vidhu Thaker, M.D., Columbia University

Publications and helpful links

General Publications

• De Rosa MC, Chesi A, McCormack S, Zhou J, Weaver B, McDonald M, Christensen S, Liimatta K, Rosenbaum M, Hakonarson H, Doege CA, Grant SFA, Hirschhorn JN, Thaker VV. Characterization of Rare Variants in MC4R in African American and Latino Children With Severe Early-Onset Obesity. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2961-2970. doi: 10.1210/jc.2018-02657.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: November 25, 2013
• First Submitted That Met QC Criteria: November 25, 2013
• First Posted (Estimated): December 2, 2013

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: genetics; obesity; childhood; early-onset
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: IRB-P00009351

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified data will be deposited in public databases at the end of the study