title: The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI.
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.
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhao
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bradfield
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Kim
authors.forename: Kiran
authors.initials: K
authors.lastname: Annaiah
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Kelly
authors.initials: K
authors.lastname: Thomas
authors.forename: Maria
authors.initials: M
authors.lastname: Garris
authors.forename: Edward C
authors.initials: EC
authors.lastname: Frackelton
authors.forename: F George
authors.initials: FG
authors.lastname: Otieno
authors.forename: Julie L
authors.initials: JL
authors.lastname: Shaner
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Smith
authors.forename: Rosetta M
authors.initials: RM
authors.lastname: Chiavacci
authors.forename: Robert I
authors.initials: RI
authors.lastname: Berkowitz
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
mesh_terms: D000293:Adolescent; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007223:Infant; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014481:United States