Early origins of cardiometabolic risk factors:life course epidemiology and pathways

• Main Author: Choudhary, P. (Priyanka)
• Other Authors: Sebert, S. (Sylvain), Järvelin, M. (Marjo-Riitta), Lowry, E. (Estelle)
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Oulun yliopisto 2021
• Subjects: biopsychosocial; birthweight; cardiometabolic risk factors; early adversities; maternal prenatal health; maternal smoking; smoking; aineenvaihduntasairaudet riskitekijät; biopsykososiaalisuus; syntymäpaino; tupakointi; varhaiset riskitekijät; äidin raskaudenaikainen terveys; äidin raskausajan tupakointi; Northern Finland
• Online Access: http://urn.fi/urn:isbn:9789526229263

Abstract Non-communicable diseases, chiefly cardiovascular diseases and type 2 diabetes (T2D), are major causes of mortality and morbidity worldwide. The literature expands on multifactorial risks that extend beyond biological dimension, including interplays with social, psychological and environmental factors, setting in place the foundations for shaping future health outcomes. However, the link between genetic and environmental causative mechanisms and temporal trajectories since gestation is poorly understood. In this thesis, a holistic approach was achieved by assessing the: 1) Variations in DNA methylation at the GFI1 locus in relation to smoking to build the epigenetic link, mediating the latent association of maternal smoking on offspring’s cardiometabolic health in adulthood; 2) Synergy between maternal prenatal biological, psychological and social factors in cumulatively influencing offspring’s birth outcomes and; 3) Early origins of T2D tracked through longitudinal risk of adiposity and modulating associations of lifestyle factors. Studies were primarily conducted in the Northern Finland Birth Cohorts 1966 and 1986, and multiple cohorts were included in studiesI & II to enable robustness and generalizability. The first study showed associations of the hypomethylation of epigenetic sites at the GFI1 locus, associated with fetal exposures to maternal smoking, on adult triglyceride, adiposity, and blood pressure levels. The second study yielded a four factor structure between the biopsychosocial variables thata clustered into biological and psychosocial factors and showed comparable associations with birth outcomes. The third study provided clear evidence that in a contemporary birth cohort, lower birth weight remains a major risk for T2D. Overweight patterns in childhood associated with increased risks of developing T2D when continued into adulthood. This research serves as a proof of concept for the ongoing debate of the lifecourse consequences of early life adversities. The body of evidence ...