Genetic studies of gestational diabetes mellitus in 21,813 Chinese women

Abstract

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 {gamma}-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.