Genetic risk scores demonstrate the cumulative association of single nucleotide polymorphisms in gut microbiome-related genes with obesity phenotypes in preschool age children

the STRONG Kids Research Team, Sharon M Donovan, Margarita De L Teran-Garcia

Research output: Contribution to journalArticle

Abstract

Background: Childhood obesity is a nutrition-related disease with multiple underlying aetiologies. While genetic factors contribute to obesity, the gut microbiome is also implicated through fermentation of nondigestible polysaccharides to short-chain fatty acids (SCFA), which provide some energy to the host and are postulated to act as signalling molecules to affect expression of gut hormones. Objective: To study the cumulative association of causal, regulatory, and tagged single nucleotide polymorphisms (SNPs) within genes involved in SCFA recognition and metabolism with obesity. Design: Study participants were non-Hispanic White (NHW, n = 270) and non-Hispanic Black (NHB, n = 113) children (2-5 years) from the Synergistic Theory and Research on Obesity and Nutrition Group (STRONG) Kids 1 Study. SNP variables were assigned values according to the additive, dominant, or recessive inheritance models. Weighted genetic risk scores (GRS) were constructed by multiplying the reassigned values by independently generated β-coefficients or by summing the β-coefficients. Ethnicity-specific SNPs were selected for inclusion in GRS by cohort. Results: GRS were directly associated with body mass index (BMI) z-score. The models explained 3.75%, 12.9%, and 26.7% of the variance for NHW/NHB, NHW, and NHB (β = 0.89 [CI: 0.43-1.35], P = 0.0002; β = 0.78 [CI: 0.54-1.03], P < 0.0001; β = 0.74 [CI: 0.51–0.97], P < 0.0001). Conclusion: This analysis supports the cumulative association of several candidate genetic variants selected for their role in SCFA signalling, transport, and metabolism with early-onset obesity. These data strengthen the concept that microbiome influences obesity development through host genes interacting with SCFA.

Original languageEnglish (US)
Article numbere12530
JournalPediatric Obesity
Volume14
Issue number9
DOIs
StatePublished - Jan 1 2019

Fingerprint

Preschool Children
Volatile Fatty Acids
Single Nucleotide Polymorphism
Obesity
Phenotype
Genes
Pediatric Obesity
Microbiota
Fermentation
Polysaccharides
Body Mass Index
Gastrointestinal Microbiome
Hormones
Research

Keywords

  • childhood obesity
  • genetic risk score
  • gut microbiome

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Health Policy
  • Nutrition and Dietetics
  • Public Health, Environmental and Occupational Health

Cite this

@article{05a1029d8e2940d6a4fc0eda8f1d9656,
title = "Genetic risk scores demonstrate the cumulative association of single nucleotide polymorphisms in gut microbiome-related genes with obesity phenotypes in preschool age children",
abstract = "Background: Childhood obesity is a nutrition-related disease with multiple underlying aetiologies. While genetic factors contribute to obesity, the gut microbiome is also implicated through fermentation of nondigestible polysaccharides to short-chain fatty acids (SCFA), which provide some energy to the host and are postulated to act as signalling molecules to affect expression of gut hormones. Objective: To study the cumulative association of causal, regulatory, and tagged single nucleotide polymorphisms (SNPs) within genes involved in SCFA recognition and metabolism with obesity. Design: Study participants were non-Hispanic White (NHW, n = 270) and non-Hispanic Black (NHB, n = 113) children (2-5 years) from the Synergistic Theory and Research on Obesity and Nutrition Group (STRONG) Kids 1 Study. SNP variables were assigned values according to the additive, dominant, or recessive inheritance models. Weighted genetic risk scores (GRS) were constructed by multiplying the reassigned values by independently generated β-coefficients or by summing the β-coefficients. Ethnicity-specific SNPs were selected for inclusion in GRS by cohort. Results: GRS were directly associated with body mass index (BMI) z-score. The models explained 3.75{\%}, 12.9{\%}, and 26.7{\%} of the variance for NHW/NHB, NHW, and NHB (β = 0.89 [CI: 0.43-1.35], P = 0.0002; β = 0.78 [CI: 0.54-1.03], P < 0.0001; β = 0.74 [CI: 0.51–0.97], P < 0.0001). Conclusion: This analysis supports the cumulative association of several candidate genetic variants selected for their role in SCFA signalling, transport, and metabolism with early-onset obesity. These data strengthen the concept that microbiome influences obesity development through host genes interacting with SCFA.",
keywords = "childhood obesity, genetic risk score, gut microbiome",
author = "{the STRONG Kids Research Team} and Wang, {Anthony A.} and Kristen Harrison and Salma Musaad and Donovan, {Sharon M} and Teran-Garcia, {Margarita De L}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/ijpo.12530",
language = "English (US)",
volume = "14",
journal = "Pediatric obesity",
issn = "2047-6302",
publisher = "Wiley-Blackwell for the International Association for the Study of Obesity",
number = "9",

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TY - JOUR

T1 - Genetic risk scores demonstrate the cumulative association of single nucleotide polymorphisms in gut microbiome-related genes with obesity phenotypes in preschool age children

AU - the STRONG Kids Research Team

AU - Wang, Anthony A.

AU - Harrison, Kristen

AU - Musaad, Salma

AU - Donovan, Sharon M

AU - Teran-Garcia, Margarita De L

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Childhood obesity is a nutrition-related disease with multiple underlying aetiologies. While genetic factors contribute to obesity, the gut microbiome is also implicated through fermentation of nondigestible polysaccharides to short-chain fatty acids (SCFA), which provide some energy to the host and are postulated to act as signalling molecules to affect expression of gut hormones. Objective: To study the cumulative association of causal, regulatory, and tagged single nucleotide polymorphisms (SNPs) within genes involved in SCFA recognition and metabolism with obesity. Design: Study participants were non-Hispanic White (NHW, n = 270) and non-Hispanic Black (NHB, n = 113) children (2-5 years) from the Synergistic Theory and Research on Obesity and Nutrition Group (STRONG) Kids 1 Study. SNP variables were assigned values according to the additive, dominant, or recessive inheritance models. Weighted genetic risk scores (GRS) were constructed by multiplying the reassigned values by independently generated β-coefficients or by summing the β-coefficients. Ethnicity-specific SNPs were selected for inclusion in GRS by cohort. Results: GRS were directly associated with body mass index (BMI) z-score. The models explained 3.75%, 12.9%, and 26.7% of the variance for NHW/NHB, NHW, and NHB (β = 0.89 [CI: 0.43-1.35], P = 0.0002; β = 0.78 [CI: 0.54-1.03], P < 0.0001; β = 0.74 [CI: 0.51–0.97], P < 0.0001). Conclusion: This analysis supports the cumulative association of several candidate genetic variants selected for their role in SCFA signalling, transport, and metabolism with early-onset obesity. These data strengthen the concept that microbiome influences obesity development through host genes interacting with SCFA.

AB - Background: Childhood obesity is a nutrition-related disease with multiple underlying aetiologies. While genetic factors contribute to obesity, the gut microbiome is also implicated through fermentation of nondigestible polysaccharides to short-chain fatty acids (SCFA), which provide some energy to the host and are postulated to act as signalling molecules to affect expression of gut hormones. Objective: To study the cumulative association of causal, regulatory, and tagged single nucleotide polymorphisms (SNPs) within genes involved in SCFA recognition and metabolism with obesity. Design: Study participants were non-Hispanic White (NHW, n = 270) and non-Hispanic Black (NHB, n = 113) children (2-5 years) from the Synergistic Theory and Research on Obesity and Nutrition Group (STRONG) Kids 1 Study. SNP variables were assigned values according to the additive, dominant, or recessive inheritance models. Weighted genetic risk scores (GRS) were constructed by multiplying the reassigned values by independently generated β-coefficients or by summing the β-coefficients. Ethnicity-specific SNPs were selected for inclusion in GRS by cohort. Results: GRS were directly associated with body mass index (BMI) z-score. The models explained 3.75%, 12.9%, and 26.7% of the variance for NHW/NHB, NHW, and NHB (β = 0.89 [CI: 0.43-1.35], P = 0.0002; β = 0.78 [CI: 0.54-1.03], P < 0.0001; β = 0.74 [CI: 0.51–0.97], P < 0.0001). Conclusion: This analysis supports the cumulative association of several candidate genetic variants selected for their role in SCFA signalling, transport, and metabolism with early-onset obesity. These data strengthen the concept that microbiome influences obesity development through host genes interacting with SCFA.

KW - childhood obesity

KW - genetic risk score

KW - gut microbiome

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U2 - 10.1111/ijpo.12530

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