Increasing evidence links epigenetic variation to anthropometric and metabolic measures. Leptin signalling regulates appetite and energy expenditure, and in pregnancy is important for nutrient supply to the foetus. Maternal metabolic health and foetal growth are linked to infant blood leptin gene (LEP) methylation, which has been cross-sectionally associated with adolescent obesity. Despite this, few studies have explored the relationship between infant LEP methylation and childhood anthropometry, or the impact of genetic variation on these relationships. Using a prospective birth cohort, we investigated whether blood LEP promoter methylation at birth and 12 months predicts weight and adiposity at 4-years. Locus-specific methylation data was analysed by partial correlation tests and multivariable linear regression. There was weak evidence of an association of birth LEP methylation with anthropometry measures at 4 years. Methylation at a specific site (cg19594666) at 12 months was inversely associated with 4-year weight (r = -0.11, p = 0.02) and body-mass index (BMI) (r = -0.13, p = 0.007), which persisted following adjustment for weight at birth and at 12 months. Neither association was influenced by genotype. We report the first evidence of an association between LEP methylation in infancy and childhood weight. Replication in additional cohorts is required to determine if this relationship persists.

中文翻译：

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12 个月时血液中 LEP 基因启动子的甲基化和 4 岁时的 BMI——一项基于人群的队列研究。

越来越多的证据将表观遗传变异与人体测量和代谢测量联系起来。瘦素信号调节食欲和能量消耗，在怀孕期间对胎儿的营养供应很重要。母体代谢健康和胎儿生长与婴儿血液瘦素基因 (LEP) 甲基化有关，这与青少年肥胖具有横断面关联。尽管如此，很少有研究探讨婴儿 LEP 甲基化与儿童人体测量学之间的关系，或遗传变异对这些关系的影响。我们使用前瞻性出生队列研究了出生时和 12 个月时血液 LEP 启动子甲基化是否能预测 4 岁时的体重和肥胖。通过偏相关检验和多变量线性回归分析基因座特异性甲基化数据。有弱证据表明出生 LEP 甲基化与 4 岁时的人体测量学测量值相关。12 个月时特定部位 (cg19594666) 的甲基化与 4 年体重 (r = -0.11, p = 0.02) 和体重指数 (BMI) (r = -0.13, p = 0.007) 呈负相关，且持续存在在调整出生时和 12 个月时的体重后。两种关联都不受基因型的影响。我们报告了婴儿期 LEP 甲基化与儿童体重之间关联的第一个证据。需要在其他队列中进行复制以确定这种关系是否持续。在调整出生时和 12 个月时的体重后，这种情况仍然存在。两种关联都不受基因型的影响。我们报告了婴儿期 LEP 甲基化与儿童体重之间关联的第一个证据。需要在其他队列中进行复制以确定这种关系是否持续。在调整出生时和 12 个月时的体重后，这种情况仍然存在。两种关联都不受基因型的影响。我们报告了婴儿期 LEP 甲基化与儿童体重之间关联的第一个证据。需要在其他队列中进行复制以确定这种关系是否持续。