Whole genome sequencing and analysis of 4,053 individuals in trios and mother-infant duos from the Born in Guangzhou Cohort Study

Abstract Large-scale birth cohorts that recruit trios/duos families are essential resource for determining the genetic and environmental contribution to maternal-infant’s health. While large-scale genomic studies of unrelated individuals were carried out around the world, genomic study based on birth cohorts is scarce, especially in China and Asia. Here, we present the Phase I genomic study of the Born in Guangzhou Cohort Study (BIGCS), which consists of the analysis of the whole genome sequencing data of 4,053 Chinese participants in trios or mother-infant duos living in South China. We identify 18.3 million novel genetic variants and construct a reference panel that enables more accurate genotype imputation for individuals of Chinese ancestry. We identify a new ancestral component specific to southern Chinese and for the first time, have dissected the genetic relationship of 10 Chinese dialects. We reveal seven novel East-Asian specific genetic associations with total bile acid, gestational weight gain and lipid metabolism level in the maternal peripheral or fetal cord blood and have recognized the distinction of genetic effect on the same trait between adults and infants. Using inter-generational mendelian randomization, we have dissected five mechanisms related to maternal and fetal genetic effect of seven adult phenotypes on six fetal growth-related pregnancy outcomes. Our findings fill the gap of the missing diversity in human genetics and demonstrate the great value of genomic study of birth cohort in advancing the worldwide genetic knowledge and maternal-infant health.