Abstract
Adverse Childhood Experiences are stressful and traumatic events occurring before the age of eighteen shown to cause mental and physical health problems, including increased risk of obesity. Obesity remains an ongoing national challenge with no predicted solution. We examine a subset of the Healthy Nevada Project, focusing on a multi-ethnic cohort of 15,886 sequenced participants with recalled adverse childhood events, to study how ACEs and their genotype-environment interactions affect BMI. Specifically, the Healthy Nevada Project participants sequenced by the Helix Exome+ platform were cross-referenced to their electronic medical records and social health determinants questionnaire to identify: 1) the effect of ACEs on BMI in the absence of genetics; 2) the effect of genotype-environment interactions on BMI; 3) how these gene-environment interactions differ from standard genetic associations of BMI. The study found very strong significant associations between the number of adverse childhood experiences and adult obesity. Additionally, we identified fifty-five common and rare variants that exhibited gene-interaction effects including three variants in the CAMK1D gene and four variants in LHPP; both genes are linked to schizophrenia. Surprisingly, none of the variants identified with interactive effects were in canonical obesity-related genes. Here we show the delicate balance between genes and environment, and how the two strongly influence each other.
Highlights
Adverse Childhood Experiences or Events (ACEs) are defined as traumatic events and unsafe environments occurring in children before the age of 18 (Felitti et al, 1998)
Results of the ACE questionnaire when applied to the Healthy Nevada Project (HNP) closely followed those of the original Center for Disease ControlKaiser Permanente ACE Study (Centers for Disease Control and Prevention, 2019)
The genome-wide environment interaction study (GWEIS) results presented in this manuscript focus on HNPEU participants due to its large cohort size
Summary
Childhood trauma and adversity has long been linked with a greater risk of negative adult health outcomes (Felitti et al, 1998; McCrory et al, 2011; Merrick et al, 2019; Jones et al, 2020; Park et al, 2020). Genotype-Environment Interactions of BMI experiencing at least four ACEs; the CDC reports that at least five of the top ten leading causes of death are associated with ACEs (Merrick et al, 2019; Jones et al, 2020; Park et al, 2020). Obesity is another challenge for North America (TFAH, 2020). The general rate of obesity is higher in lowto-middle income countries than in high-income countries, highlighting an association of lower income with higher BMI (Levine, 2011; Kim et al, 2018)
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