Developmental origins of psycho-cardiometabolic multimorbidity in adolescence and their underlying pathways through methylation markers: A two cohort’s study

Abstract Understanding the biological mechanisms behind multimorbidity patterns in adolescence is important as they may act as intermediary risk factor for long-term health. We aimed to explore relationship between prenatal exposures and adolescent’s psycho-cardiometabolic intermediary traits mediated through epigenetic biomarkers, using structural equation modelling (SEM). We used data from mother-child dyads from pregnancy and adolescents at 16–17 years from two prospective cohorts: Northern Finland Birth Cohort 1986 (NFBC1986) and Raine Study from Australia. Factor analysis was applied to generate two different latent factor structures: a) prenatal exposures and b) adolescence psycho-cardiometabolic intermediary traits. Furthermore, three types of epigenetic biomarkers were included: 1) DNA methylation score for maternal smoking during pregnancy (DNAmMSS), 2) DNAm age estimate PhenoAge and 3) DNAm estimate for telomere length (DNAmTL). We observed similar factor structure was observed between both cohorts yielding three prenatal factors BMI (Body Mass Index), SOP (Socio-Obstetric-Profile) and Lifestyle, and four adolescent factors: Anthropometric, Insulin-Triglycerides, Blood Pressure and Mental health. In the SEM pathways, stronger direct effects of F1 prenatal -BMI (NFBC1986 = ß: 0.27; Raine = ß: 0.39) and F2 prenatal -SOP (ß: -0.11) factors were observed on adolescent psycho-cardiometabolic multimorbidity. The indirect effect of the prenatal latent factors through epigenetic markers was mediated from DNAmTL and DNAmMSS going through PhenoAge (NFBC1986 = ß: 0.04; Raine = ß: 0.14), consistently in both cohorts ( P < 0.001). The present study exemplifies an evidence-based approach validated in two birth cohorts to demonstrate consistent shared influences of prenatal exposures mediated through epigenetic markers in the offspring on their psycho-cardiometabolic multimorbidity in adolescence.