The Born in Guangzhou Cohort Study enables generational genetic discoveries

• 成果类型: Article
• 署名作者: Huang, Shujia; Liu, Siyang; Huang, Mingxi; He, Jian-Rong; Wang, Chengrui; Wang, Tianyi; Feng, Xiaotian; Kuang, Yashu; Lu, Jinhua; Gu, Yuqin; Xia, Xiaoyan; Lin, Shanshan; Zhou, Wenhao; Fu, Qiaomei; Xia, Huimin; Qiu, Xiu
• 署名单位: Guangzhou Medical University; Sun Yat Sen University; Guangzhou Medical University; Chinese Academy of Sciences; Institute of Vertebrate Paleontology & Paleoanthropology, CAS; Chinese Academy of Sciences; University of Chinese Academy of Sciences, CAS; Guangzhou Medical University; Guangzhou Medical University; Guangzhou Medical University; Guangzhou Medical University; Guangzhou Medical University
• 刊物名称: Nature
• ISSN/ISSBN: 0028-4635
• DOI: 10.1038/s41586-023-06988-4
• 发表日期: 2024-02-15
• 页码: 565-+
• 关键词: asymmetric cell-division; radial organization; population history; arabidopsis root; cyclin-d; protein; admixture; CHOICE; birth; deep

摘要

Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health(1). Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study(2) (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.