Novel Genetic Loci Identified for the Pathophysiology of Childhood Obesity in the Hispanic Population

Genetic variants responsible for susceptibility to obesity and its comorbidities among Hispanic children have not been identified. The VIVA LA FAMILIA Study was designed to genetically map childhood obesity and associated biological processes in the Hispanic population. A genome-wide association stu...

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Bibliographic Details
Published in:PloS one 2012-12, Vol.7 (12), p.e51954-e51954
Main Authors: Comuzzie, Anthony G, Cole, Shelley A, Laston, Sandra L, Voruganti, V. Saroja, Haack, Karin, Gibbs, Richard A, Butte, Nancy F, Crawford, Dana C
Format: Article
Language:English
Subjects:
ABO system
Adolescent
Analysis
anthropometric measurements
Anthropometry
Antioxidants
Biological activity
Biology
blood serum
Body composition
Body composition (biology)
Body Composition - genetics
Body mass index
Body weight
CCR3 receptor
Child
Child, Preschool
Childhood obesity
Children
comorbidity
Diet
Disease susceptibility
Energy consumption
Energy expenditure
Energy Metabolism
Exercise
fasting
Fasting - metabolism
Gene loci
Genes
Genetic aspects
Genetic diversity
Genetic Loci
Genetic markers
Genetic Markers - genetics
Genetic Predisposition to Disease
Genetic variance
genetic variation
Genome-wide association studies
genome-wide association study
Genome-Wide Association Study - methods
Genomes
Genomics
Genotype
Genotyping
glucose
Glucose - metabolism
Hispanic Americans
Hispanic Americans - genetics
Hispanics
Hormones
Hormones - genetics
Hormones - metabolism
Humans
Inflammation
Inflammation - genetics
Inflammation - metabolism
Localization
Loci
Medicine
Metabolites
Monocyte chemoattractant protein 1
Nutrition research
Obesity
Obesity - ethnology
Obesity - genetics
Obesity - metabolism
Pathogenesis
pathophysiology
phenotype
Phenotyping
Physical activity
Polymorphism, Single Nucleotide
Population genetics
Population studies
Single nucleotide polymorphisms
Single-nucleotide polymorphism
Sleep
Substrates
thyrotropin
triacylglycerols
Triglycerides
Triglycerides - metabolism
variants
Young Adult
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Summary:Genetic variants responsible for susceptibility to obesity and its comorbidities among Hispanic children have not been identified. The VIVA LA FAMILIA Study was designed to genetically map childhood obesity and associated biological processes in the Hispanic population. A genome-wide association study (GWAS) entailed genotyping 1.1 million single nucleotide polymorphisms (SNPs) using the Illumina Infinium technology in 815 children. Measured genotype analysis was performed between genetic markers and obesity-related traits i.e., anthropometry, body composition, growth, metabolites, hormones, inflammation, diet, energy expenditure, substrate utilization and physical activity. Identified genome-wide significant loci: 1) corroborated genes implicated in other studies (MTNR1B, ZNF259/APOA5, XPA/FOXE1 (TTF-2), DARC, CCR3, ABO); 2) localized novel genes in plausible biological pathways (PCSK2, ARHGAP11A, CHRNA3); and 3) revealed novel genes with unknown function in obesity pathogenesis (MATK , COL4A1). Salient findings include a nonsynonymous SNP (rs1056513) in INADL (p = 1.2E-07) for weight; an intronic variant in MTNR1B associated with fasting glucose (p = 3.7E-08); variants in the APOA5-ZNF259 region associated with triglycerides (p = 2.5-4.8E-08); an intronic variant in PCSK2 associated with total antioxidants (p = 7.6E-08); a block of 23 SNPs in XPA/FOXE1 (TTF-2) associated with serum TSH (p = 5.5E-08 to 1.0E-09); a nonsynonymous SNP (p = 1.3E-21), an intronic SNP (p = 3.6E-13) in DARC identified for MCP-1; an intronic variant in ARHGAP11A associated with sleep duration (p = 5.0E-08); and, after adjusting for body weight, variants in MATK for total energy expenditure (p = 2.7E-08) and in CHRNA3 for sleeping energy expenditure (p = 6.0E-08). Unprecedented phenotyping and high-density SNP genotyping enabled localization of novel genetic loci associated with the pathophysiology of childhood obesity.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0051954