Abordagens de big data e genômica funcional na análise da interação entre baixo peso ao nascer e índice de massa corporal

Abstract

Introduction: Low birth weight (LBW) is a significant early life adversity linked to numerous risk factors and metabolic dysfunctions throughout life. Poor fetal growth, as assessed by birth weight, is also associated with neurometabolic alterations and increased obesity risk later in life. This study investigates the socioeconomic and health-related factors contributing to LBW in Brazil and explores interindividual differences in the development of obesity among children exposed to such adversity. Methods: Data from the Global Health Data Exchange (GHDx) and official Brazilian government sources from 1995 to 2017 were analyzed, totaling 338 state-year observations using a lagged analysis. Factors such as smoking, alcohol use, high blood pressure, high body mass index (HBMI), and diet were evaluated for their association with LBW. Additionally, data from four cohorts were used to calculate methylation scores and expression-based polygenic risk scores (ePRS) to assess the moderation effect on the association between birth weight and BMI. Results: Reproductive-age population exposure to smoking, alcohol, high systolic blood pressure, and HBMI were positively associated with LBW. Socioeconomic factors like GDP per capita and access to primary care mitigated these associations. A 1- point increase in LBW SEV was associated with an increase in HBMI in peripubertal children, an effect also moderated by GDP per capita and primary care access. In the cohort studies, NAcc ePRS interacted with birth weight in association with BMI at various ages, with variations observed across different populations and tissues. Discussion: The findings underscore the impact of socioeconomic and health-related factors on LBW and its long-term consequences on obesity risk. Functional genomics approaches, such as methylation scores and ePRS, provide insights into individual differences in response to prenatal adversity, informing the development of precision preventive measures. These results highlight the importance of improving public policies related to healthcare and welfare to mitigate the burden of being born small and address the variability in obesity outcomes among affected children.