Genetic epidemiology of early growth and cardiometabolic diseases

Eunice Kennedy Shriver National Institute Of Child Health & Human Development

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Abstract

Genetic epidemiology of early growth and links with cardiometabolic diseases Many cardiometabolic diseases in later life have links with early life growth. Advances in understanding the mechanism of early growth variation will provide early intervention opportunities for cardiometabolic outcomes. Dr. Tekola-Ayele's research aims to determine genetic mechanisms in early growth variations and links between early growth and cardiometabolic diseases in multi-ancestral populations. To achieve this goal, his group focuses on two overarching complementary research themes at the maternal-placental-fetal interface: genetics of fetal growth and placental epigenome/transcriptome. Maternal genetic risk of type 2 diabetes (T2D) has been associated with fetal growth, but the influence of genetic ancestry has not been fully understood. We found that the association between maternal genetic risk for T2D and fetal growth began in early-second trimester and was influenced by genetic ancestry distance from a reference population (Hum Genomics. 2024 Jul 19;18(1):81; PMID: 39030631). Genetic distance was also shown to modify the link between maternal obesity and risk of large for gestational age (birthweight >90th percentile) (Int J Obes (Lond). 2025 Apr 12. doi: 10.1038/s41366-025-01783-9; PMID: 40221546). Genetic modulation of placental function can vary by context-specific factors such as fetal sex, which have profound implication in placental function and pregnancy outcomes. We identified sex differences in placenta genetic, epigenetic, and transcriptomic regulation, providing key insights about neonatal and adult diseases shaped early by sex (Nat Commun. 2025 May 1;16(1):4004; PMID: 40312437). We identified novel placental methylation sites associated with the weight and functional efficiency of the placenta (Epigenomics. 2025 Jun;17(9):589-598. doi: 10.1080/17501911.2025.2510190; PMID: 40415454). Maternal depressive symptoms sustained during first and second trimesters has been found to be associated with accelerated epigenetic aging of placenta, potentially suggesting placental aging as an underlying link between poor maternal mental health during pregnancy and pregnancy complications (Am J Obstet Gynecol MFM. 2024;6(1):101237; PMID: 38012987). Obstetric factors such as parity modify the association of birthweight polygenic score with fetal growth, demonstrating the important role of non-genetic factors that may negate genetic risk (Sci Rep. 2025 Jul 31;15(1):27915. doi: 10.1038/s41598-025-10415-1; PMID: 40745191).