On October 9, an impressive collaboration between the BGI Life Science Research Institute, BGI Genomics, Wuhan Children’s Hospital, Shenzhen Maternity and Child Healthcare Hospital, Sun Yat-sen University, Xiamen University, Suzhou Municipal Hospital, South China University of Technology, Guangzhou Women and Children’s Medical Center, and Xiamen University’s Affiliated Women and Children’s Hospital resulted in six groundbreaking research papers published as a cover story in the internationally renowned journal Cell Genomics. These studies systematically explored biochemical phenotypes during pregnancy, maternal-fetal metabolic indicators, and the genetic basis of gestational diabetes, highlighting the critical role genetic factors play in maternal and infant health and offering new perspectives for pregnancy health management.
In comparison to the abundant research into cancer and cardiovascular diseases, studies focusing on the genetics of pregnancy have been notably sparse. This research utilized novel methodologies developed by the team, providing the first comprehensive genetic association analyses of various biochemical markers observed during prenatal check-ups. The team successfully identified 410 genes linked to these phenotypic groups—genes that correlate with routine blood tests and assessments of liver and kidney function. Among these, 116 genes (or 28%) were newly discovered, and 31 were found to have specific associations with particular pregnancy-related conditions, such as serum creatinine levels and the HELLP syndrome gene. These genes predominantly enriched pathways related to estrogen resistance and immune response, significantly connected to the immune and female reproductive systems, thereby offering new insights into understanding how genetic factors influence pregnancy phenotypes and maternal health.
Using tandem mass spectrometry, the researchers screened 84 metabolic indicators during pregnancy (including amino acids and vitamins) and identified 53 related genes, with 23 being novel findings. The study also uncovered that the same metabolite exhibited different genetic effects in pregnant versus non-pregnant young and middle-aged women, revealing unique genetic regulatory mechanisms for metabolic levels during pregnancy. Further Mendelian randomization analysis indicated potential causal relationships between these maternal metabolic indicators and 15 age-related diseases and phenotypes. These findings provide valuable scientific evidence for understanding the genetic basis of maternal metabolic elements during pregnancy and their impact on maternal and infant health, as well as insights for developing personalized nutritional supplement strategies.
The researchers analyzed 75 neonatal metabolic compounds and their ratios, estimating an average heritability of 76% for these metabolites within the newborn population. They identified 30 significant genomic signals, including 11 novel “metabolite-gene” associations. Further exploration utilizing single-cell transcriptome data revealed that these genes were specifically expressed in neonatal liver and renal tubular cells, providing reference points for understanding the factors influencing neonatal metabolite concentrations.
The study also identified 25 genes associated with blood glucose levels. Notably, it confirmed established links between gestational diabetes and the CDKAL1 and MTNR1B genes, while also revealing for the first time an association between fasting blood glucose during pregnancy and the estrogen receptor gene ESR1 in Asian populations. Previously reported in connection with hypertension, this study’s genetic correlation and Mendelian randomization analysis further delineate the complex interplay between gestational blood glucose levels, hormone regulation, and hypertension. Based on these findings, the research team developed a novel risk prediction algorithm for gestational diabetes, providing fresh insights into managing blood glucose during pregnancy.
Furthermore, the research team has made the methodologies used in this study publicly available in a specialized methodological paper within the same journal issue, facilitating future research. All studies adhered strictly to ethical research protocols, and the data involved were anonymized and approved by the Human Genetic Resources Management Office of the Ministry of Science and Technology.
