Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry.
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.
Grant
Struan F A
SF
Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. grants@chop.edu
Bradfield
Jonathan P
JP
Zhang
Haitao
H
Wang
Kai
K
Kim
Cecilia E
CE
Annaiah
Kiran
K
Santa
Erin
E
Glessner
Joseph T
JT
Thomas
Kelly
K
Garris
Maria
M
Frackelton
Edward C
EC
Otieno
F George
FG
Shaner
Julie L
JL
Smith
Ryan M
RM
Imielinski
Marcin
M
Chiavacci
Rosetta M
RM
Li
Mingyao
M
Berkowitz
Robert I
RI
Hakonarson
Hakon
H
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*
C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4