Using MR approach, 14 metabolites were found to be associated with postprandial glucose in WEs, while in SAs a distinct panel of 11 metabolites were identified. Results: This study identified 15 novel genome-wide significant (GWS) SNPs associated with tyrosine in the FOXN and SLC13A2 genes and 1 novel GWS SNP (currently in no known gene) associated with acetate in SAs. Additional GWAS and MR on 22 composite measures of metabolite classes were also conducted. Following this, a one-sample Mendelian Randomisation (MR) approach was applied for each metabolite against fasting glucose and 2-hr post glucose at 26-28 weeks gestation. First, we performed 292 GWASs to identify ethnic-specific genetic variants associated with each metabolite (P ≤ 1 x 10-5) in the Born and Bradford cohort (3688 SA and 3354 WE women). Methods: To address this, we paired metabolite and genomic data to evaluate the causal effect of 146 distinct metabolic characteristics on gestational dysglycemia in SAs and WEs. Recent evidence suggests that underlying metabolic difference contribute to this disparity, but an investigation of causality is required. Prevalence of GDM varies between ethnicities, with South Asians (SAs) experiencing up to three times the risk compared to white Europeans (WEs). Introduction: Gestational diabetes mellitus (GDM) is the most common pregnancy complication worldwide and is associated with short- and long-term health implications for both mother and child. 4Leeds Institute for Data Analytics, University of Leeds, Leeds, United Kingdom.3Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom.2Public Health Science Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.1School of Food Science and Nutrition, University of Leeds, Leeds, United Kingdom.
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