Center for Applied Genomics, Abramson Research Center, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Nat Genet. 2012 May;44(5):526-31. doi: 10.1038/ng.2247.
Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).
多种遗传变异与成人肥胖有关，少数与儿童重度肥胖有关；然而，在确定遗传对常见早发性肥胖的影响方面进展较少。我们对 14 项研究进行了北美、澳大利亚和欧洲的合作荟萃分析，这些研究包括 5530 例病例（体重指数（BMI）≥第 95 百分位）和 8318 例对照（BMI<第 50 百分位），这些病例和对照均为欧洲血统。在 9 个独立数据集（2818 例病例和 4083 例对照）中，我们对 8 个新发现的与 P<5×10(-6)相关的信号进行了前瞻性研究，在 13q14 处 OLFM4 附近观察到两个产生全基因组显著联合 P 值的位点（rs9568856；P=1.82×10(-9)；比值比（OR）=1.22）和在 17q21 处 HOXB5 内（rs9299；P=3.54×10(-9)；OR=1.14）。当包含两个极端儿童肥胖队列（2214 例病例和 2674 例对照）时，这两个位点仍显示出相关性。这两个位点在前一个成人 BMI 荟萃分析中也显示出了一致的方向关联(1)。
