Genetic studies of gestational diabetes mellitus in 21,813 Chinese women
medrxiv(2023)
摘要
Gestational diabetes mellitus (GDM) is a common complication of pregnancy with adverse effects on both mothers and fetuses. The relationship between GDM and clinical information has been largely investigated; however, the role of laboratory features and genetic components in GDM are relatively understudied, especially in the Chinese population. In this study, we recruited 21,813 pregnant Chinese women and investigated the risk factors for GDM from both environmental and genetic aspects. In addition to the serum fasting glucose and urine glucose measured in the first trimester, our study revealed the close relations of γ-glutamyl transferase, prealbumin, and uric acid to GDM. The GWAS and subsequent conditional & joint association analysis identified four genome-wide significant SNPs, rs35261542, rs4712530, rs3781637, and rs12225378, mapped on CDKAL1 and MTNR1B . The allele frequencies of the latter three SNPs showed substantial differences in European and East Asian populations. The ancient DNA analysis demonstrated that mutation of rs3781637 was originally appeared in an ancient Chinese in the Holocene period. This result might provide useful reference for explaining the distinct genetic background of GDM in different populations. Considering both clinical measurements and genetic components, we constructed an early prediction model for GDM by using only a dozen indicators and achieved acceptable prediction performance. We believe that our study will certainly become an important reference for the genetic study of GDM and will have important implications for elucidating the genetic mechanisms of GDM.
### 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:
Both the institutional review board of Wuhan Children 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
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