Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, Room 3204, Bethesda, 20892-7004, USA.
Sci Rep. 2021 Jan 8;11(1):48. doi: 10.1038/s41598-020-80084-9.
Childhood obesity is a global public health problem. Understanding the molecular mechanisms that underlie early origins of childhood obesity can facilitate interventions. Consistent phenotypic and genetic correlations have been found between childhood obesity traits and birth weight (a proxy for in-utero growth), suggesting shared genetic influences (pleiotropy). We aimed to (1) investigate whether there is significant shared genetic influence between birth weight and childhood obesity traits, and (2) to identify genetic loci with shared effects. Using a statistical approach that integrates summary statistics and functional annotations for paired traits, we found strong evidence of pleiotropy (P < 3.53 × 10) and enrichment of functional annotations (P < 1.62 × 10) between birth weight and childhood body mass index (BMI)/obesity. The pleiotropic loci were enriched for regulatory features in skeletal muscle, adipose and brain tissues and in cell lines derived from blood lymphocytes. At 5% false discovery rate, 6 loci were associated with birth weight and childhood BMI and 13 loci were associated with birth weight and childhood obesity. Out of these 19 loci, one locus (EBF1) was novel to childhood obesity and one locus (LMBR1L) was novel to both birth weight and childhood BMI/obesity. These findings give evidence of substantial shared genetic effects in the regulation of both fetal growth and childhood obesity.
儿童肥胖是一个全球性的公共卫生问题。了解导致儿童肥胖的早期根源的分子机制，可以促进干预措施的实施。儿童肥胖特征与出生体重（宫内生长的代表）之间存在一致的表型和遗传相关性，这表明存在共同的遗传影响（多效性）。我们的目的是：（1）研究出生体重和儿童肥胖特征之间是否存在显著的共同遗传影响；（2）确定具有共同效应的遗传位点。我们使用一种统计方法，该方法整合了配对特征的汇总统计数据和功能注释，发现出生体重和儿童体重指数（BMI）/肥胖之间存在强烈的多效性证据（P < 3.53 × 10）和功能注释的富集（P < 1.62 × 10）。多效性位点在骨骼肌、脂肪和脑组织以及血液淋巴细胞衍生的细胞系中富集了调节特征。在假发现率为 5%时，有 6 个位点与出生体重和儿童 BMI 相关，13 个位点与出生体重和儿童肥胖相关。在这 19 个位点中，有一个位点（EBF1）是儿童肥胖的新发现，有一个位点（LMBR1L）是出生体重和儿童 BMI/肥胖的新发现。这些发现为胎儿生长和儿童肥胖的调节存在大量共同遗传效应提供了证据。
