The Born in Guangzhou Cohort Study enables generational genetic discoveries

Nature. 2024 Feb;626(7999):565-573. doi: 10.1038/s41586-023-06988-4. Epub 2024 Jan 31.

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.

MeSH terms

  • Adult
  • Bile Acids and Salts / metabolism
  • China / ethnology
  • Cohort Studies*
  • Cordocentesis
  • Female
  • Fetus / embryology
  • Gene-Environment Interaction*
  • Genetic Variation* / genetics
  • Genome, Human* / genetics
  • Gestational Weight Gain
  • Humans
  • Infant
  • Infant, Newborn
  • Lipids / blood
  • Maternal Exposure
  • Parturition
  • Phenotype*
  • Prenatal Exposure Delayed Effects*
  • Prospective Studies

Substances

  • Bile Acids and Salts
  • Lipids