The genetic risk of gestational diabetes in South Asian women

Abstract

South Asian women are at increased risk of developing gestational diabetes (GDM). Few studies have investigated the genetic contributions to GDM risk. We investigated the association of a type 2 diabetes (T2D) polygenic risk score (PRS), on its own, and with GDM risk factors, on GDM-related traits using data from two birth cohorts in which South Asian women were enrolled during pregnancy. 837 and 4,372 pregnant South Asian women from the SouTh Asian BiRth CohorT (START) and Born in Bradford (BiB) cohort studies underwent a 75-gram glucose tolerance test. PRSs were derived using GWAS results from an independent multi-ethnic study (~18% South Asians). Associations with fasting plasma glucose (FPG); 2h post-load glucose (2hG); area under the curve glucose; and GDM were tested using linear and logistic regressions. The population attributable fraction (PAF) of the PRS was calculated. Every 1 SD increase in the PRS was associated with a 0.085 mmol/L increase in FPG ([95%CI=0.07-0.10], P=2.85 × 10-20); 0.21 mmol/L increase in 2hG ([95%CI=0.16-0.26], P=5.49 × 10-16); and a 45% increase in the risk of GDM ([95%CI=32-60%], P=2.27 × 10-14), independent of parental history of diabetes and other GDM risk factors. PRS tertile 3 accounted for 12.5% of the population's GDM alone, and 21.7% when combined with family history. A few weak PRS and GDM risk factors interactions modulating FPG and GDM were observed. Together, these results show that a T2D PRS and family history of diabetes are strongly and independently associated with multiple GDM-related traits in women of South Asian descent, an effect that could be modulated by other environmental factors.

A culturally tailored personaliseD nutrition intErvention in South ASIan women at risk of Gestational Diabetes Mellitus (DESI-GDM): a randomised controlled trial protocol

“… 74 A final limitation is that the genetic risk carried by South Asian women may overwhelm the effects of our dietary intervention. 12 …”

“…GDM increases the risk of future T2DM and CVD. The development of GDM is influenced by several factors, including prepregnancy body mass index (BMI), 9 10 family history, 11 genetics 12 13 and notably ethnicity 11 14 15 and diet. 11 14 16–18 SA are two times more likely to develop GDM relative to white European women, 14 15 and risk factors for future T2DM in the offspring, including higher birth weight, more adipose tissue and reduced insulin sensitivity, are more common in SA infants of mothers with GDM than infants born to mothers without GDM.…”

Associations between diet quality and dietary patterns and gestational diabetes mellitus in a low‐risk cohort of pregnant women in Australia: a cross‐sectional study

“…Due to the different scoring scales between the DASH and MDS, both scores were standardised for the logistic regression analysis 45,46 . Potential covariates were identified a priori from the literature and included known risk factors for GDM including BMI, 47 maternal age 48,49 and being born in South Asia 7,50 . All models were therefore adjusted for age (continuous), ethnicity (categorical [Asian and African, European and American, Australian/New Zealander]) and BMI in early pregnancy (continuous).…”

“…45,46 Potential covariates were identified a priori from the literature and included known risk factors for GDM including BMI, 47 maternal age 48,49 and being born in South Asia. 7,50 All models were therefore adjusted for age (continuous), ethnicity (categorical [Asian and African, European and American, Australian/New Zealander]) and BMI in early pregnancy (continuous). It is worth mentioning that the analysis adjusted with and without BMI was examined, and the results were marginally the same; thus the fully adjusted models were presented.…”

Beyond the individual: Socio‐ecological factors impacting activity after gestational diabetes mellitus

“…This is important to consider given that women with South Asian heritage are twice as likely to develop Gestational Diabetes and have a subsequent higher risk of progression to Type 2 Diabetes. 67,68 Future research should aim to explore the barriers and facilitators of PA for women from different ethnic backgrounds. This could involve removing the eligibility criteria of being able to communicate in English and working with interpreters to increase participation.…”