Kresovich Jacob K, Zheng Yinan, Cardenas Andres, Joyce Brian T, Rifas-Shiman Sheryl L, Oken Emily, Gillman Matthew W, Hivert Marie-France, Baccarelli Andrea A, Hou Lifang
Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL USA.
Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center and Department of Preventive Medicine, Northwestern University, Chicago, IL USA.
Clin Epigenetics. 2017 Aug 15;9:86. doi: 10.1186/s13148-017-0384-9. eCollection 2017.
Excess adiposity in childhood is associated with numerous adverse health outcomes. As this condition is difficult to treat once present, identification of risk early in life can help inform and implement strategies to prevent the onset of the condition. We performed an epigenome-wide association study to prospectively investigate the relationship between cord blood DNA methylation and adiposity measurements in childhood.
We measured genome-wide DNA methylation from 478 children in cord blood and measured overall and central adiposity via skinfold caliper measurements in early (range 3.1-3.3 years) and mid-childhood (age range 7.3-8.3 years) and via dual X-ray absorptiometry (DXA) in mid-childhood. Final models were adjusted for maternal age at enrollment, pre-pregnancy body mass index, education, folate intake during pregnancy, smoking during pregnancy, and gestational weight gain, and child sex, race/ethnicity, current age, and cord blood cell composition.
We identified four promoter proximal CpG sites that were associated with adiposity as measured by subscapular (SS) and triceps (TR) ratio (SS:TR) in early childhood, in the genes , , , and . We additionally identified one gene body CpG site associated with early childhood SS + TR on ; this site was nominally associated with SS + TR in mid-childhood. Higher methylation at one promoter proximal CpG site in was also associated with SS:TR in mid-childhood. In regional analyses, methylation at an exonal region of was positively associated with SS:TR in early childhood. Finally, we identified regions of two long, non-coding RNAs which were associated with SS:TR (LOC100049716) and fat-free mass index (LOC102723493) in mid-childhood.
This analysis identified novel CpG loci associated with adiposity outcomes. However, our results suggest little consistency across the various adiposity outcomes tested, particularly among the more accurate DXA measurements of body composition. We recommend using caution when interpreting these associations.
儿童期肥胖与众多不良健康后果相关。由于这种情况一旦出现就难以治疗，因此在生命早期识别风险有助于制定和实施预防该病症发作的策略。我们进行了一项全表观基因组关联研究，以前瞻性地调查脐带血DNA甲基化与儿童期肥胖测量值之间的关系。
我们测量了478名儿童脐带血中的全基因组DNA甲基化，并在儿童早期（范围3.1 - 3.3岁）和中期（年龄范围7.3 - 8.3岁）通过皮褶厚度测量法测量总体和中心性肥胖，并在儿童中期通过双能X线吸收法（DXA）进行测量。最终模型根据母亲入组时的年龄、孕前体重指数、教育程度、孕期叶酸摄入量、孕期吸烟情况、孕期体重增加以及儿童的性别、种族/民族、当前年龄和脐带血细胞组成进行了调整。
我们在儿童早期发现了四个启动子近端CpG位点，它们与通过肩胛下（SS）和三头肌（TR）比值（SS:TR）测量的肥胖相关，这些位点位于基因 、 、 和 中。我们还在 上鉴定了一个与儿童早期SS + TR相关的基因体CpG位点；该位点在儿童中期与SS + TR呈名义上的关联。 中一个启动子近端CpG位点的较高甲基化也与儿童中期的SS:TR相关。在区域分析中， 一个外显子区域的甲基化与儿童早期的SS:TR呈正相关。最后，我们确定了两个长链非编码RNA区域，它们在儿童中期与SS:TR（LOC100049716）和去脂体重指数（LOC102723493）相关。
该分析确定了与肥胖结果相关的新CpG位点。然而，我们的结果表明，在测试的各种肥胖结果中，一致性较差，特别是在更准确的身体成分DXA测量中。我们建议在解释这些关联时谨慎行事。
