title: BMD-associated variation at the Osterix locus is correlated with childhood obesity in females.
abstract: 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 1106 obese children (BMI ≥ 95th percentile) and 5997 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 2867 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.
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: Haitao
authors.initials: H
authors.lastname: Zhang
authors.forename: Frank D
authors.initials: FD
authors.lastname: Mentch
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Patrick M A
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: Edward C
authors.initials: EC
authors.lastname: Frackelton
authors.forename: Rosetta M
authors.initials: RM
authors.lastname: Chiavacci
authors.forename: Robert I
authors.initials: RI
authors.lastname: Berkowitz
authors.forename: Babette S
authors.initials: BS
authors.lastname: Zemel
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
mesh_terms: D000293:Adolescent; D000483:Alleles; D015992:Body Mass Index; D015519:Bone Density; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics*; D014481:United States; D044465:White People
chemical_list: D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors