Genetic analysis of 104 pregnancy phenotypes in 39,194 Chinese women

Maternity is a special period in a woman life that involves substantial physiological, psychological, and hormonal changes. These changes may cause alterations in many clinical measurements during pregnancy, which can be used to monitor and diagnose maternal disorders and adverse postnatal outcomes. Exploring the genetic background of these phenotypes is key to elucidating the pathogenesis of pregnancy disorders. In this study, we conducted a large-scale molecular biology analysis of 104 pregnancy phenotypes based on genotype data from 39,194 Chinses women. Genome-wide association analysis identified a total of 407 trait-locus associations, of which 75.18% were previously reported. Among the 101 novel associations for 37 phenotypes, some were potentially pregnancy-specific and worth further experimental investigation. For example, ESR1 with fasting glucose, hemoglobin, hematocrit, and several leukocytoses; ZSCAN31 with blood urea nitrogen. We further performed pathway-based analysis and uncovered at least one significant pathway for 24 traits, in addition to previously known functional pathways, novel findings included birthweight with Reactome signaling by NODAL, twin pregnancy with Reactome mitotic G1-G1/S phases. The partitioning heritability analysis recapitulated known trait-relevant tissue/cell types, and also discovered interesting results including twin pregnancy with embryoid bodies cell-type enrichment, the delivery type cesarean section with fallopian tube, and birth weight with ovary and embryonic stem cells. In terms of both sample size and the variety of phenotypes, our work is one of the largest genetic studies of pregnancy phenotypes across all populations. We believe that this study will provide a valuable resource for exploring the genetic background of pregnancy phenotypes and also for further research on pregnancy-related diseases and adverse neonatal outcomes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the Central Guidance on Local Science and Technology Development Fund of Hubei Province (2022BGE261), National Natural Science Foundation of China (32171441 and 32000398), Guangdong-Hong Kong Joint Laboratory on Immunological and Genetic Kidney Diseases (2019B121205005), Top Medical Young Talents (2019) of Hubei Province, Guangdong Provincial Key Laboratory of Genome Read and Write (2017B030301011), Open project of BGI-Shenzhen, Shenzhen 518000 China (BGIRSZ20200008) ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The institutional review board in Wuhan Children's Hospital (2021R062) and the BGI Research (BGI-IRB 21088) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors