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

Vanderbilt University, United States of America
PLoS ONE (Impact Factor: 3.23). 12/2012; 7(12):e51954. DOI: 10.1371/journal.pone.0051954
Source: PubMed


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.

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Available from: Anthony G Comuzzie, Oct 07, 2015
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    • "Maternal BMI and child ' s birth weight were the only predictors of maternal perception of their child ' s weight Increased maternal BMI = higher child BMI and decreased maternal perception of child weight Comuzzie et al . ( 2012 ) 815 Hispanic Children Genetically map childhood obesity and associated biological processes in the Hispanic population Genetic factors increased the risk of childhood obesity"
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    • "CNT- NAP2 located in chromosome 7 was among the most significant region identified by haploPS (P unadjusted = 5.61E-08; P adjusted = 0.0028), F ST (P = 2.47E-07) and LSBL. CNT- NAP2 has been associated with BMI as well as visceral and subcutaneous adipose tissue (Comuzzie et al. 2012; Velez Edwards et al. 2012; Fox et al. 2012). "
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    • "Importantly, these same SNPs associate significantly with decreased incidence of developing other autoimmune diseases that share similar immunologic mechanisms with RA: namely, ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and multiple sclerosis (MS) [39]. Conversely, GPSM3 SNPs show risk association with type I diabetes and autoimmune thyroid disease [39] [40], and GPSM3 genetic polymorphisms have also been linked with atopic dermatitis and childhood obesity, two diseases also characterized by chronic inflammation [41] [42]. The GPSM3 locus on chromosome 6 is located very near to the Notch4 gene locus and is found within the densely-packed and disease-relevant human leukocyte antigen (HLA) region [39] [42], raising the possibility that GPSM3 SNP variants mark functional polymorphisms in other closely associated genes. "
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