Investigating effect modification between childhood maltreatment and genetic risk for cardiovascular disease in the UK Biobank.
Investigating effect modification between childhood maltreatment and genetic risk for cardiovascular disease in the UK Biobank.
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在英国生物库中调查儿童虐待与心血管疾病的遗传风险之间的修改。
DOI：
10.1371/journal.pone.0285258
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Carter, Alice
中科院分区：
文献类型：
--
作者：
Urquijo, Helena D.;Soares, Ana Goncalves R.;Fraser, Abigail;Howe, Laura;Carter, Alice
心血管疾病(CVD)受遗传和环境因素的影响。儿童期虐待与心血管疾病有关，并可能改变心血管危险因素的遗传易感性。我们使用了100,833名英国白种人英国生物库参与者(57%为女性，平均年龄为55.9岁)的遗传和表型数据。我们回归了9种心血管危险因素/疾病(饮酒、体重指数[BMI]、低密度脂蛋白胆固醇、终生吸烟行为、收缩压、房颤、冠心病、2型糖尿病和中风)与其各自的多基因评分(PG)和自我报告的童年虐待经历。通过在回归模型中加入乘积项(PGS*虐待)，在加法和乘法尺度上测试效果修正。在加性量表上，儿童期虐待加剧了遗传易感性对较高体重指数的影响(P效应修正：0.003)。未受儿童期虐待的个体在BMI PGS中每增加一次SD，BMI就增加0.12 SD(95%CI：0.11，0.13)，而在所有类型的儿童期虐待中，BMI增加0.17 SD(95%CI：0.14，0.19)。在乘性尺度上，BMI也得到了类似的结果，尽管这些结果不能经受Bonferroni校正。几乎没有证据表明儿童期虐待与其他结果有关的效果改变，或者性别特有的效果改变。我们的研究表明，在儿童时期遭受虐待的个体中，对较高BMI的遗传易感性的影响可能会适度加剧。然而，基因*环境的相互作用可能不是儿童期虐待受害者经历的过度心血管疾病负担的主要原因。
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.
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影响因子：
20.1
作者：
Bhatnagar A
通讯作者：
Bhatnagar A
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