title: Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry.
abstract: Recently a modest, but consistently, replicated association was demonstrated between obesity and the single-nucleotide polymorphism (SNP), rs17782313, 3' of the MC4R locus as a consequence of a meta-analysis of genome-wide association (GWA) studies of the disease in white populations. We investigated the association in the context of the childhood form of the disease utilizing data from our ongoing GWA study in a cohort of 728 European-American (EA) obese children (BMI > or =95th percentile) and 3,960 EA controls (BMI <95th percentile), as well as 1,008 African-American (AA) obese children and 2,715 AA controls. rs571312, rs10871777, and rs476828 (perfect surrogates for rs17782313) yielded odds ratios in the EA cohort of 1.142 (P = 0.045), 1.137 (P = 0.054), and 1.145 (P = 0.042); however, there was no significant association with these SNPs in the AA cohort. When investigating all 30 SNPs present on the Illumina BeadChip at this locus, again there was no evidence for association in AA cases when correcting for the number of tests employed. As such, variants 3' to the MC4R locus present on the genotyping platform utilized confer a similar magnitude of risk of obesity in white children as to their adult white counterparts but this observation did not extend to AAs.
authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. grants@chop.edu
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bradfield
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Kim
authors.forename: Kiran
authors.initials: K
authors.lastname: Annaiah
authors.forename: Erin
authors.initials: E
authors.lastname: Santa
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: Marcin
authors.initials: M
authors.lastname: Imielinski
authors.forename: Rosetta M
authors.initials: RM
authors.lastname: Chiavacci
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.forename: Robert I
authors.initials: RI
authors.lastname: Berkowitz
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
mesh_terms: D000293:Adolescent; D001741:Black or African American / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006801:Humans; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D044465:White People / Q000208:ethnology / Q000235:genetics*
chemical_list: C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4