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BMD‐Associated Variation at the Osterix Locus Is Correlated With Childhood Obesity in Females
Author(s) -
Zhao Jianhua,
Bradfield Jonathan P.,
Li Mingyao,
Zhang Haitao,
Mentch Frank D.,
Wang Kai,
Sleiman Patrick M.A.,
Kim Cecilia E.,
Glessner Joseph T.,
Frackelton Edward C.,
Chiavacci Rosetta M.,
Berkowitz Robert I.,
Zemel Babette S.,
Hakonarson Hakon,
Grant Struan F.A.
Publication year - 2011
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2010.324
Subject(s) - genome wide association study , medicine , percentile , obesity , childhood obesity , locus (genetics) , genetic epidemiology , osteoporosis , body mass index , bone mineral , genetic association , epidemiology , cohort , allele , demography , endocrinology , genetics , genotype , biology , single nucleotide polymorphism , gene , overweight , statistics , mathematics , sociology
Recent genome wide association studies (GWAS) have revealed a number of genetic variants robustly associated with bone mineral density (BMD) and/or osteoporosis. Evidence from epidemiological and clinical studies has shown an association between BMD and BMI, presumably as a consequence of bone loading. We investigated the 23 previously published BMD GWAS‐derived loci in the context of childhood obesity by leveraging our existing genome‐wide genotyped European American cohort of 1,106 obese children (BMI ≥95th percentile) and 5,997 controls (BMI <95th percentile). Evidence of association was only observed at one locus, namely Osterix ( SP7 ), with the G allele of rs2016266 being significantly over‐represented among childhood obesity cases ( P = 2.85 × 10 −3 ). When restricting these analyses to each gender, we observed strong association between rs2016266 and childhood obesity in females (477 cases and 2,867 controls ; P = 3.56 × 10 −4 ), which survived adjustment for all tests applied. However, no evidence of association was observed among males. Interestingly, Osterix is the only GWAS locus uncovered to date that has also been previously implicated in the determination of BMD in childhood. In conclusion, these findings indicate that a well established variant at the Osterix locus associated with increased BMD is also associated with childhood obesity primarily in females.