Interaction between adverse childhood experiences and polygenic risk in patients with bipolar disorder

Abstract

The interaction between genes and environment often occurs when they depend on one another. We hypothesized that adverse childhood experiences (ACEs) would interact with genetic predispositions to bipolar disorder (BD), demonstrating earlier age at onset (AAO) and worse clinical outcomes. We aimed to clarify the effects of the interaction between ACEs and genetic susceptibility using polygenic risk score (PRS) on AAO and clinical outcomes. Single nucleotide polymorphisms and clinical data, including ACEs, were obtained from the Bipolar Genomic Study, which contains a large sample of BD participants. A total of 1615 subjects with BD I were obtained and divided into two groups according to the presence or absence of ACEs and an additional four groups based on the number of ACEs (none versus one versus two versus ≥ three types). ACEs was evaluated using the childhood life events scale (CLES). BD–PRS was obtained from the Psychiatric Genomics Consortium, which compared BD patients and healthy controls. The BD–PRS was higher in the group with ACEs than without ACEs at most p-value thresholds. In multivariate linear regression analyses, both groups with more ACEs and higher BD–PRS were independently and interactively associated with an earlier AAO of BD; however, only greater ACEs were associated with worsened clinical outcome. These findings highlight the clinical importance of evaluating ACEs and polygenic risk in research of the etiology of BD.

The Impact of ACEs on BMI: An Investigation of the Genotype-Environment Effects of BMI

“…Exactly 526 (0.32%) of the questions were missing/blank, stemming from 384 participants, yielding a very small degree of missingness. The ACE score was computed as the sum of affirmative responses a participant reported (Gilbert et al, 2015;Park et al, 2020;Tsai et al, 2020). A participant with two ACEs, for example, encountered two different types of adverse childhood events at least one time each by the age of 18.…”

“…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). 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).…”

“…ACEs range across several of the Social Determinants of Health (SDOH) categories as defined by the Center for Disease Control (CDC), including safe housing, violence, education, income, access to (nutritious) food; all SDOH factors have been shown to have profound impact on individuals' physical health and quality of life. Numerous national studies indicate the seriousness and incidence of ACEs with prevalence as high as 63.6% of adults experiencing at least one ACE and 16% 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).…”

Using phenome-wide association studies and the SF-12 quality of life metric to identify profound consequences of adverse childhood experiences on adult mental and physical health in a Northern Nevadan population

“…Numerous national studies indicate the seriousness of ACEs with prevalence as high as 67% of adults experiencing at least one ACE and 16% experiencing at least four ACEs. The CDC reports that at least five of the top ten leading causes of death are associated with ACEs ( 18 , 19 , 21 , 37 ). Other research highlights the implications and consequences of ACEs, including risk for chronic disease such as asthma, cancer, diabetes, heart disease, inflammatory disorders, obesity and others ( 4 , 6 , 9 , 10 , 18 , 19 , 21 , 38 ).…”

“…The CDC reports that at least five of the top ten leading causes of death are associated with ACEs ( 18 , 19 , 21 , 37 ). Other research highlights the implications and consequences of ACEs, including risk for chronic disease such as asthma, cancer, diabetes, heart disease, inflammatory disorders, obesity and others ( 4 , 6 , 9 , 10 , 18 , 19 , 21 , 38 ). The relationship between ACEs and mental illness is also known ( 32 , 39 – 44 ): relationships with mental disorders such as adult depression, anxiety, eating disorders, schizophrenia, substance abuse, suicide, among others have been clearly established ( 23 – 25 , 30 , 39 , 42 , 44 ).…”