Descriptive statistics of study sample, stratified by sex.

Descriptive statistics of study sample, stratified by sex.</p

Study exclusion criteria.

*CVD = stroke, atrial fibrillation, coronary heart disease or risk factor type 2 diabetes. **Participants can be missing more than one variable, so the total excluded is less than the sum of the missing data of all traits.</p

Summary characteristics for each GWAS used to derive external weights in polygenic scores.

Summary characteristics for each GWAS used to derive external weights in polygenic scores.</p

STROBE statement—checklist of items that should be included in reports of observational studies.

STROBE statement—checklist of items that should be included in reports of observational studies.</p

Effect modification by exposure to childhood maltreatment on genetic predisposition to cardiovascular risk factors and disease on the multiplicative scale at P<5x10^-8.

Analyses were adjusted for age, sex and 40 genetic principal components. Traits are grouped according to whether they are binary or continuous. BMI = body mass index; LDL-C = low-density lipoprotein cholesterol; SBP = systolic blood pressure; PGS = polygenic score.</p

S1 File -

Cardiovascular disease (CVD) is influenced by genetic and environmental factors. Childhood maltreatment is associated with CVD and may modify genetic susceptibility to cardiovascular risk factors. We used genetic and phenotypic data from 100,833 White British UK Biobank participants (57% female; mean age = 55.9 years). We regressed nine cardiovascular risk factors/diseases (alcohol consumption, body mass index [BMI], low-density lipoprotein cholesterol, lifetime smoking behaviour, systolic blood pressure, atrial fibrillation, coronary heart disease, type 2 diabetes, and stroke) on their respective polygenic scores (PGS) and self-reported exposure to childhood maltreatment. Effect modification was tested on the additive and multiplicative scales by including a product term (PGS*maltreatment) in regression models. On the additive scale, childhood maltreatment accentuated the effect of genetic susceptibility to higher BMI (Peffect modification: 0.003). Individuals not exposed to childhood maltreatment had an increase in BMI of 0.12 SD (95% CI: 0.11, 0.13) per SD increase in BMI PGS, compared to 0.17 SD (95% CI: 0.14, 0.19) in those exposed to all types of childhood maltreatment. On the multiplicative scale, similar results were obtained for BMI though these did not withstand to Bonferroni correction. There was little evidence of effect modification by childhood maltreatment in relation to other outcomes, or of sex-specific effect modification. Our study suggests the effects of genetic susceptibility to a higher BMI may be moderately accentuated in individuals exposed to childhood maltreatment. However, gene*environment interactions are likely not a major contributor to the excess CVD burden experienced by childhood maltreatment victims.</div

Effect modification by exposure to childhood maltreatment on genetic predisposition to cardiovascular risk factors and disease on the additive scale at P<5x10^-8.

Analyses were adjusted for age, sex and 40 genetic principal components. Traits are grouped according to whether they are binary or continuous. BMI = body mass index; LDL-C = low-density lipoprotein cholesterol; SBP = systolic blood pressure; PGS = polygenic score.</p