Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, 19104, USA.
Am J Hum Genet. 2010 Nov 12;87(5):661-6. doi: 10.1016/j.ajhg.2010.09.014. Epub 2010 Oct 14.
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 5(th) 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 (< 50(th) 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.
美国儿童和成人的肥胖患病率在过去十年中急剧上升。基因组拷贝数变异（CNVs）强烈提示存在极度肥胖和并存发育迟缓的患者。为了补充这些先前的研究，我们通过检查 BMI 处于前 5%但排除了平均值三个标准差以上的任何受试者的儿童来研究常见儿童肥胖症的 CNVs，以减少队列中的严重病例。我们对我们的 1080 名定义为欧洲裔美国人（EA）儿童肥胖病例和 2500 名瘦对照（BMI<第 50 百分位）的队列进行了全基因组 CNV 调查，这些对照者使用 550000 个 SNP 标记进行了基因分型。在一个独立的 1479 名非洲裔美国人（AA）儿童肥胖病例和 1575 名瘦对照者队列中评估了阳性发现。我们确定了 17 个 CNV 位点，这些位点至少在三个 EA 病例中是独特的，并且以前在公共领域中没有报道过，并且通过定量 PCR 进行了验证。其中 8 个位点（47.1%）也仅在 AA 病例中复制（6 个缺失和 2 个重复）。复制的缺失位点包括 EDIL3、S1PR5、FOXP2、TBCA、ABCB5 和 ZPLD1，而复制的重复位点包括 KIF2B 和 ARL15。当 AA 队列被作为发现集进行研究时，我们还观察到 EPHA6-UNQ6114 位点缺失的证据。尽管这些变体可能单独罕见，但我们的结果表明 CNVs 导致了具有欧洲和非洲血统的常见儿童肥胖症患者的遗传易感性。
