title: Role of BMI-associated loci identified in GWAS meta-analyses in the context of common childhood obesity in European Americans.
abstract: Obesity is a serious health concern for children and adolescents, particularly in Western societies, where its incidence is now considered to have reached epidemic proportions. A number of genetic determinants of adult BMI have already been established through genome wide association studies (GWAS), most recently from the GIANT meta-analysis of such datasets combined. In this current study of European Americans, we examined the 32 loci detected in that GIANT study in the context of common childhood obesity within a cohort of 1,097 cases (defined as BMI ≥95th percentile), together with 2,760 lean controls (defined as BMI <50th percentile), aged between 2 and 18 years old. Nine of these single-nucleotide polymorphims (SNPs) yielded at least nominal evidence for association with common childhood obesity, namely at the FTO, TMEM18, NRXN3, MC4R, SEC16B, GNPDA2, TNNI3K, QPCTL, and BDNF loci. However, overall 28 of the 32 loci showed directionally consistent effects to that of the adult BMI meta-analysis. We conclude that among the 32 loci that have been reported to associate with adult BMI in the largest meta-analysis of BMI to date, at least nine also contribute to the determination of common obesity in childhood in European Americans, 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: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sleiman
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Kim
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Sandra
authors.initials: S
authors.lastname: Deliard
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Thomas
authors.forename: Edward C
authors.initials: EC
authors.lastname: Frackelton
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
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; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D009765:Obesity / Q000235:genetics*; D015143:Philadelphia; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*