278-OR: Ancestry-Specific Genetic Risk Scores of Type 2 Diabetes and Longitudinal Fetal Growth in a Race-Ethnic Diverse Population

It is well documented that maternal type 2 diabetes (T2D) is related to fetal overgrowth. Further, maternal T2D genetic risk score (GRS) has been associated with increased offspring birthweight. However, the earliest gestational age when fetal growth starts to be associated with T2D GRS is unknown. We investigated the associations between maternal T2D GRS and longitudinal ultrasound measured fetal weight. We included 1,513 women of diverse race/ethnicity from the NICHD Fetal Growth Studies-singleton cohort. Women were enrolled at gestational weeks 8-13 and randomly assigned to four ultrasound schedules to capture weekly fetal growth. Genome-wide single nucleotide polymorphisms (SNPs) previously known to be associated with T2D in European-, African-, and Asian- ancestry populations (380, 104, and 19 SNPs, respectively) were used to calculate weighted GRS. The analysis involved European GRS for Whites and Hispanics, African GRS for Blacks and Asian GRS for Asians. Associations between quartiles of GRS and fetal weight were adjusted for pre-pregnancy BMI, population structure, fetal sex and gestational weeks. Among Whites, the highest quartile of European GRS was related to a 53.8 g increment in fetal weight (95% CI 19.2-88.5 g) over the pregnancy, and across 24 to 40 weeks (from 15.8 g increase at week 24 to 196.0 g increase at week 40). Similar findings were observed in analysis that excluded women with impaired glucose tolerance. African-, European- and Asian-GRSs were not significantly associated with fetal weight among other race/ethnic groups. Genetic susceptibility to T2D based on European-specific GRS among Whites was related to increased fetal weight starting at week 24 even among normal glycemia women, suggesting an early influence of genetic factors on fetal growth. Absence of similar associations in non-Whites is likely due to the small number of established T2D genetic loci warranting the need for genetic studies of T2D in diverse populations. Disclosure M. Ouidir: None. X. Zeng: None. S. Chatterjee: None. C. Zhang: None. F. Tekola-ayele: None.