Abstract：
Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health1. Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study2 (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health.
摘要：
以大规模为目标的基因组研究，前瞻性出生队列是了解遗传和环境对人类健康影响的基本策略1。尽管如此，这样的研究仍然很少，特别是在亚洲。在这里，我们介绍了出生在广州队列研究2（BIGCS）的I期基因组研究，其中包括对4053名中国人的测序和分析，主要由居住在中国南方的三人组或母婴二人组组成。我们的分析揭示了新的遗传变异，一个高质量的参考面板，和BIGCS内的精细局部遗传结构。值得注意的是,我们确定了以前未报告的东亚特异性遗传关联与母体总胆汁酸，妊娠期体重增加和婴儿脐带血特征。此外,我们观察到母亲和婴儿中普遍存在的年龄特异性遗传效应对血脂水平的影响.在一项探索性的代际孟德尔随机化分析中，我们估计了7种成人表型对7项胎儿生长相关测量的母体推定因果效应和胎儿遗传效应.这些发现阐明了东亚人群中母亲和早年特征之间的遗传联系，并为将来研究复杂的遗传学相互作用奠定了基础。宫内暴露和早期生活经验在塑造长期健康。
