Article

The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI.

Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Obesity (Impact Factor: 4.39). 06/2009; 17(12):2254-7. DOI: 10.1038/oby.2009.159
Source: PubMed

ABSTRACT The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. A number of genetic determinants of adult BMI have already been established through genome-wide association (GWA) studies. In this study, we examined 25 single-nucleotide polymorphisms (SNPs) corresponding to 13 previously reported genomic loci in 6,078 children with measures of BMI. Fifteen of these SNPs yielded at least nominally significant association to BMI, representing nine different loci including INSIG2, FTO, MC4R, TMEM18, GNPDA2, NEGR1, BDNF, KCTD15, and 1q25. Other loci revealed no evidence for association, namely at MTCH2, SH2B1, 12q13, and 3q27. For the 15 associated variants, the genotype score explained 1.12% of the total variation for BMI z-score. We conclude that among 13 loci that have been reported to associate with adult BMI, at least nine also contribute to the determination of BMI in childhood as demonstrated by their associations in our pediatric cohort.

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    • "The first robust association was reported for FTO (fat mass and obesity associated) (Frayling et al., 2007). This association was joined by insulin-induced gene 2 (INSIG2), melanocortin 4 receptor (MC4R), transmembrane protein 18 (TMEM18), glucosamine- 6-phosphate deaminase 2 (GNPDA2), neuronal growth regulator 1 (NEGR1), brain-derived neurotrophic factor (BDNF), and potassium channel tetramerization domain containing 15 (KCTD15), as associated with pediatric obesity (den Hoed et al., 2010; Zhao et al., 2009). Intensive research in molecular genetics continues on other well-established loci of obesityassociated genes, including those that encode the uncoupling proteins (Oppert et al., 1994; Ricquier, Casteilla, & Bouillaud, 1991), peroxisome proliferator-activated receptor (PPAR)g (Lefebvre et al., 1998; Vidal- Puig et al., 1997), low-density lipoprotein receptor (Morris, Zee, & Robinson, 1994), hormone-sensitive lipase (Klannemark et al., 1998; Stich et al., 1997), beta adrenergic receptors (Reynisdottir, Ellerfeldt, 52 Fangnian Wang et al. "
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    • "Article reference: 1) Loos et al., 2009; 2) Hinney et al., 2007; 3) Loos et al., 2008; 4) Willer et al., 2009; 5) Zhao et al., 2009; 6) Thorleifson et al., 2009 "
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