12th Annual IGSS Conference • October 28-29, 2021

Integrating Genetics and the Social Sciences 2021

Life-course victimization and CRP related DNA methylation among LGB adults

Aura Ankita Mishra, University of North Carolina at Chapel Hill

Evidence suggests that children who experience caregiver abuse may be exposed to multiple types of violence victimization (Finkelhor, Ormrod, & Turner, 2007; Finkelhor, Turner, Shattuck, & Hamby, 2015). Moreover, these early-life abuse exposures are strongly correlated with other types of victimization at later developmental periods such as adolescence and adulthood (Finkelhor, Ormrod, & Turner, 2007; Schwab-Reese, Currie, Mishra, & Peek-Asa, 2018). Lesbian, gay, bisexual (LGB) individuals, in particular, are more vulnerable to violence victimization and multiple violence victimization (or poly-victimization) throughout life (Schwab-Reese, Currie, Mishra, & Peek-Asa, 2018). Life-course victimization, such as exposure to childhood abuse and intimate partner violence, has been linked to biological inflammation (Coelho, Viola, Walss‐Bass, Brietzke, & Grassi‐Oliveira, 2014; Newton et al., 2011). Inflammation may, to an extent, explain life-course victimization-related morbidity and early mortality (Rich-Edwards et al., 2010; Suglia, Clark, Boynton-Jarrett, Kressin, & Koenen, 2014; Out, Hall, Granger, Page, & Woods, 2012). Additionally, the roles of early life adversity and adult traumatic stress have been examined in epigenetic processes, particularly epigenetic changes related to immune function and inflammation (Barker et al., 2018; Miller et al., 2018; Naumova et al., 2012). To elaborate, researchers have found that greater childhood adversity was linked to inflammatory epigenetic risk and methylation of regions related to immune functioning among children (Barker et al., 2018; Naumova et al., 2012). Similarly, methylation of a CpG site in the CRP (a biomarker of inflammation) promoter region among adult survivors of trauma has also been previously established (Miller et al., 2018). However, less is known about how cumulative life-course victimization among LGB individuals (a vulnerable population for violence victimization) is associated with inflammation related epigenetic processes. Aims Therefore, to understand the association between cumulative life-course victimization and inflammation-related epigenetic mechanisms among LGB adults, two aims were tested. The first aim of this research is to replicate CpG sites that have been previously associated with CRP among LGB adults (Ligthart et al., 2016; Aim 1). The second study aim is to examine the association between cumulative life-course victimization among LGB adults and replicated CpG sites for CRP investigated in Aim 1. Data Data come from The National Longitudinal Study of Adolescent to Adult Health (Add Health). Add Health is a two-stage stratified, national cohort sample of individuals who were followed from adolescence to adulthood over five waves of data collection spanning over 24 years [Wave 1: 1994-95; Wave 2: 1996; Wave 3: 2001-2002; Wave 4: 2008; Wave 5: 2016-2018] (Harris et al., 2019). The sample for the present analysis includes 326 LGB adults with biomarker data, who also had reports of victimization exposure and serum CRP levels within four standard deviations from the mean to mimic the analytic strategy of previous literature (Ligthart et al., 2016). Measures Life-course Victimization. A count variable of life-course victimization was created using all five waves of data. The indicators of life-course victimization included – sexual, physical, and emotional abuse by a caregiver in childhood (before age 12), sexual, physical, and emotional abuse by a caregiver in adolescence (ages 12-18), criminal assault in adolescence, criminal assault in adulthood (>18), physical intimate partner violence in adulthood, and sexual assault in adulthood. Methylation of CpG sites. Venous blood was collected at Wave 5 when the participants were adults to estimate methylation patterns across CpG sites. We included 205 CpG sites from a list of 218 CpG sites that were significantly associated with CRP in a meta-analysis conducted by Ligthart and colleagues (2016; see paper for a complete list of CpGs from the meta-analysis). Thirteen CpG sites from the meta-analysis (Ligthart et al., 2016) were excluded during quality control steps. Immune Biomarkers. At Wave 5, blood samples were also collected to assess several biomarkers, including CRP. Serum CRP was log-transformed (natural log units) to account for skewness. Analytic Strategy Aim 1: We estimated linear regression models for the association between the 205 CpG sites and log-transformed serum CRP levels, correcting for multiple testing (p = 2.2173 x10-05). Several covariates were accounted for across these models - current smoking, body mass index, age, biological sex, the proportion of leukocyte cell types, recent infections and inflammatory disease, and a count of medications used in the last four weeks. Aim 2: Next, we tested multivariable linear models of the association between life-course victimization among LGB adults and significant CpG sites (8 sites) from Aim 1. The following covariates were included for Aim 2 – white blood cell proportions, age, biological sex, and race. Results Results Aim 1: Preliminary results reveal that 8 CpG sites from the original list of 205 CpG sites were significantly associated with ln-CRP for LGB adults. All 8 sites were negatively associated with serum CRP. To elaborate, negative associations indicated that lower methylation (or hypo-methylation) was associated with higher CRP levels. Results Aim 2: Greater cumulative life-course victimization among LGB adults was associated with hypo-methylation of two CpG sites - cg18942579 (Gene: TMEM49) and cg18608055 (Gene: SBNO2). Discussion Models will be re-estimated for 1) an additional sample of LGB adults and 2) specific clusters of life-course victimization among LGB adults and replicated CpG sites for CRP. Findings may provide avenues for future researchers to explore how social experiences of victimization among LGB adults impact biological processes that ultimately lead to higher morbidity and mortality over time.

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