Influence of maternal genetic determinants for glycemic traits on gestational diabetes and fetal growth in Chinese population
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AbstractBackground: The genetic basis for gestational diabetes mellitus (GDM) and its impact on fetal growth remains unclear. This study aims to evaluate the role of known genetic variants associated with type 2 diabetes (T2D) and glycaemic traits in affecting GDM and fetal growth.

Method: A total of 464 women with GDM and 1,211 controls were recruited from 3 independent cohorts in the Chinese population. GDM was diagnosed using the 2013 WHO definition. DNA samples were genotyped using the Illumina HumanOmniZhongHua-8 BeadChip, HumanOmni2.5Exome-8 BeadChip, or Global Screening Array. We imputed the genotypes using minimac 3, with 1000 Genome Project phase III data as reference panel. Using the variants identified in studies of non-pregnant individuals, we constructed five genetic risk scores (GRSs) for increased T2D risk, elevated fasting glucose and insulin, reduced insulin secretion and greater insulin resistance. In each cohort, we tested for their associations with GDM using logistic regression, with the adjustments for age, BMI and principal components (PCs). Results of individual studies were combined by meta-analysis. Associations between GRSs and neonatal traits (birthweight, birth length, ponderal index, head circumference, sum of skinfold, fat mass, cord blood glucose and c-peptide) were assessed by linear regression, adjusting for gestational age, offspring gender and maternal PCs in 954 mother-child pairs.

Results: All five GRSs were significantly associated with GDM in the meta-analysis, with a 1-unit increase in each score raising the odds of GDM by 5%–16% (0.045 < P < 1.5×10-12). A trend was observed for increased sum of skinfold with T2D GRS (P = 0.0948), but no association was observed for other neonatal traits with GRSs.

Conclusion: In conclusion, women carrying more risk alleles for glycemic traits are at higher risk for GDM. Our findings demonstrated evidence of shared genetic determinants for hyperglycaemia among pregnant and non-pregnant women.


Acknowledgement: Partially supported by the RGC Theme-based Research Scheme (T12-402/13N), Health and Medical Research Fund from the Research Fund Secretariat, Food and Health Bureau, the Government of the Hong Kong Special Administrative Region, China (Project no: 05161386), and the CUHK-SJTU Joint Research Fund.
All Author(s) ListClaudia Ha-ting Tam, Xiaoxu Huo, Lai Yuk Yuen, Ying Wang, Risa Ozaki, Junhong Leng, Alex Chi-wai Ng, Jing Li, Cadmon K.P. Lim, Weiqin Li, Albert Martin Li, Jiangnan Liu, Juliana Chung-ngor Chan, Wing Hung Tam, Xilin Yang, Ronald Ching-wan Ma
Name of ConferenceThe 11th DOHaD World Congress
Start Date of Conference20/10/2019
End Date of Conference23/10/2019
Place of ConferenceMelbourne
Country/Region of ConferenceAustralia
Year2019
LanguagesEnglish-United Kingdom

Last updated on 2020-04-06 at 12:34