# Genetics of early childhood obesity and its clinical implications

> **NIH NIH K23** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $91,649

## Abstract

PROJECT SUMMARY/ABSTRACT
The rising prevalence of severe obesity in early childhood, especially in underrepresented minorities, is a
challenge to the cardio-metabolic health of our youth. Although largely attributed to the environment, heredity
plays a significant role in determining adiposity. The influence of these genetic factors is largely undefined in
children from underrepresented minorities where the prevalence is the highest. This study seeks to identify the
rare genetic variants contributing to severe obesity in a large cohort of children with severe early onset obesity
from mixed ethnic groups. The primary goal is to explain the biology of extreme obesity by understanding the
effects of genetic variants on physiological attributes leading to extreme obesity. We hypothesize that the
burden of genetic variants related to obesity will be higher in children with severe early onset of obesity,
 The sample of subjects is selected from children with severe obesity (BMI > 120% of the 95th
percentile, equivalent to Class II obesity or higher), documented at an age less than 6 years. We have
established a large multi-institutional collaborative cohort including a prospective family study of children
attending the clinics at Boston Children’s Hospital that serve large populations of underrepresented minorities,
a cohort at Children’s Hospital of Philadelphia using data extraction from the electronic health records and
samples from the biorepository and a research cohort from the Columbia University Medical Center. For the
prospective family study, children with severe obesity and their first-degree relatives are invited to participate in
the study. In the collaborative cohort, we will perform whole exome sequencing in children with extremes of
obesity, most rapid trajectory of growth of body mass index and those with family structure favorable for
mendelian pattern of inheritance. We will perform targeted sequencing of approximately 80 genes including
those causing syndromic and non-syndromic forms of obesity, and those prioritized in the whole exome study
in all other samples. We will develop an integrated genetic risk score based on the common and identified rare
genetic variants, and correlate it with the longitudinal BMI trajectories and cardio-metabolic consequences
extracted from the electronic health records. Additionally, we will perform metabolic phenotyping including
energy intake and expenditure, body composition and hormonal response to a standard meal in a subgroup
from the extreme tails of the genetic risk scores to understand the differences in physiology leading to severe
obesity.
 Individuals of different genetic ancestries can have different patterns of genetic variation. It is possible
that studying multiple ethnicities may identify new genes. Children with rare variants of large effect, or varying
genetic risk scores could help describe differences in physiology uncovering therapeutic targets, or a response
to treatment that co...

## Key facts

- **NIH application ID:** 10445160
- **Project number:** 3K23DK110539-06S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Vidhu V. Thaker
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $91,649
- **Award type:** 3
- **Project period:** 2016-09-29 → 2023-03-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445160

## Citation

> US National Institutes of Health, RePORTER application 10445160, Genetics of early childhood obesity and its clinical implications (3K23DK110539-06S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10445160. Licensed CC0.

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