title: Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
abstract: 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.
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, USA.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Comuzzie
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Laston
authors.forename: V Saroja
authors.initials: VS
authors.lastname: Voruganti
authors.forename: Karin
authors.initials: K
authors.lastname: Haack
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Butte
mesh_terms: D000293:Adolescent; D000886:Anthropometry; D001823:Body Composition / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004032:Diet; D004734:Energy Metabolism; D005215:Fasting / Q000378:metabolism; D056426:Genetic Loci; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006630:Hispanic or Latino / Q000235:genetics*; D006728:Hormones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000208:ethnology* / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000378:metabolism; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D006728:Hormones; D014280:Triglycerides; D005947:Glucose