Aberrant growth in early stages of human life increases the risk for cardiometabolic diseases during childhood and adulthood. Little is known about the mechanisms underlying the links between early growth and later life cardiometabolic diseases, and population differences in early growth and consequent cardiometabolic outcomes. Understanding the biological pathways shared between phenotypes of early growth and adult cardiometabolic outcomes will facilitate development of interventions that benefit health across the life course. By fusing genomic and environmental data, we aim to understand genetic influences in early growth and genetic mechanisms underlying the link between early growth and cardiometabolic diseases/disparities in diverse ancestral populations. Ongoing studies aim to address the following research questions:
- Investigate genetic mechanisms in longitudinal fetal growth variations and the contribution of genetic ancestry for fetal growth differences among populations. This study is conducted using genome-wide genotype data generated from stored biospecimens collected by the NICHD Fetal Growth Studies, a U.S. multi-ethnic study of fetal growth.
- Identify shared genetic pathways between birth weight and adult cardiometabolic outcomes, and understand the influence of maternal metabolic genetic factors on offspring birth outcomes. This study examines the extent of pleiotropy and enrichment of biologically functional loci using large-scale genome-wide association study genotype data contributed by several consortia as well as the database of Genotypes and Phenotypes.
- Evaluate the potential to obtain high quality DNA from sources other than whole blood. The long-term goal of this project is to leverage existing large-scale population biobanks and use them in future genetic-epidemiology studies of early growth-cardiometabolic links. A pilot study has been designed to evaluate whether stored serum can yield sufficient DNA that is usable for future genomic research. The pilot study uses banked serum samples from the Collaborative Perinatal Project, a national pregnancy cohort of more than 48,000 women and their offspring enrolled between the years 1959 and 1966.
- Cuilin Zhang, M.D., M.P.H., Ph.D.
- Deepika Shrestha, Ph.D.
- Una Grewal, Ph.D., M.P.H.
- Jennifer Weck, Ph.D.
- Katherine Laughon Grantz, M.D., M.S.
- Marion Ouidir, Ph.D.
- Stephen Gilman, Sc.D.
- Tsegaselassie Workalemahu, M.S., Ph.D.
- Workalemahu T, Grantz KL, Grewal J, Zhang C, Louis GMB, Tekola-Ayele F. Genetic and environmental influences on fetal growth vary during sensitive periods in pregnancy. Scientific Reports. 2018; 8(1):7274. PMID: 29740100. PMCID: PMC5940684
- Tekola-Ayele F, Workalemahu T, Amare AT. High burden of birthweight-lowering genetic variants in Africans and Asians. BMC Medicine. 2018; 16(1):70. PMID: 29792231. PMCID: PMC5967042