A genome-wide study reveals copy number variants exclusive to childhood obesity cases

Joseph T. Glessner, Jonathan P. Bradfield, Kai Wang, Nagahide Takahashi, Haitao Zhang, Patrick M. Sleiman, Frank D. Mentch, Cecilia E. Kim, Cuiping Hou, Kelly A. Thomas, Maria L. Garris, Sandra Deliard, Edward C. Frackelton, F. George Otieno, Jianhua Zhao, Rosetta M. Chiavacci, Mingyao Li, Joseph D. Buxbaum, Robert I. Berkowitz, Hakon HakonarsonStruan F.A. Grant

Research output: Contribution to journalArticlepeer-review

82 Scopus citations


The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Genomic copy number variations (CNVs) have been strongly implicated in subjects with extreme obesity and coexisting developmental delay. To complement these previous studies, we addressed CNVs in common childhood obesity by examining children with a BMI in the upper 5th percentile but excluding any subject greater than three standard deviations from the mean in order to reduce severe cases in the cohort. We performed a whole-genome CNV survey of our cohort of 1080 defined European American (EA) childhood obesity cases and 2500 lean controls (< 50th percentile BMI) who were genotyped with 550,000 SNP markers. Positive findings were evaluated in an independent African American (AA) cohort of 1479 childhood obesity cases and 1575 lean controls. We identified 17 CNV loci that were unique to at least three EA cases and were both previously unreported in the public domain and validated via quantitative PCR. Eight of these loci (47.1%) also replicated exclusively in AA cases (six deletions and two duplications). Replicated deletion loci consisted of EDIL3, S1PR5, FOXP2, TBCA, ABCB5, and ZPLD1, whereas replicated duplication loci consisted of KIF2B and ARL15. We also observed evidence for a deletion at the EPHA6-UNQ6114 locus when the AA cohort was investigated as a discovery set. Although these variants may be individually rare, our results indicate that CNVs contribute to the genetic susceptibility of common childhood obesity in subjects of both European and African ancestry.

Original languageEnglish
Pages (from-to)661-666
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number5
StatePublished - 12 Nov 2010


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