The Born in Guangzhou Cohort Study enables generational genetic discoveries

Shujia Huang, Siyang Liu, Mingxi Huang, Jian-Rong He, Chengrui Wang, Tianyi Wang, Xiaotian Feng, Yashu Kuang, Jinhua Lu, Yuqin Gu, Xiaoyan Xia, Shanshan Lin, Wenhao Zhou, Qiaomei Fu, Huimin Xia () and Xiu Qiu ()
Additional contact information
Shujia Huang: Guangzhou Medical University
Siyang Liu: Shenzhen Campus of Sun Yat-sen University
Mingxi Huang: Guangzhou Medical University
Jian-Rong He: Guangzhou Medical University
Chengrui Wang: Guangzhou Medical University
Tianyi Wang: Chinese Academy of Sciences
Xiaotian Feng: Chinese Academy of Sciences
Yashu Kuang: Guangzhou Medical University
Jinhua Lu: Guangzhou Medical University
Yuqin Gu: Shenzhen Campus of Sun Yat-sen University
Xiaoyan Xia: Guangzhou Medical University
Shanshan Lin: Guangzhou Medical University
Wenhao Zhou: Guangzhou Medical University
Qiaomei Fu: Chinese Academy of Sciences
Huimin Xia: Provincial Clinical Research Center for Child Health
Xiu Qiu: Guangzhou Medical University

Nature, 2024, vol. 626, issue 7999, 565-573

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41586-023-06988-4

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