文献解读-群体基因组第一期|《对BMI的影响：探究BMI的基因型-环境效应》

关键词：应用遗传流行病学；群体测序；群体基因组；基因组变异检测；

文献简介

标题（英文）：The Impact of ACEs on BMI: An Investigation of the Genotype-Environment Effects of BMI
标题（中文）：ACEs对BMI的影响：探究BMI的基因型-环境效应
发表期刊：Behavior Genetics
作者单位：美国俄勒冈州立大学心理学系
发表年份：2022
文章地址：https://doi.org/10.3389/fgene.2022.816660

图1 文献简介

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). The original ACE questionnaire and scoring protocol contains ten Yes/No questions that examine the incidence of emotional, physical, sexual maltreatment, neglect, substance abuse within the household, mental illness in the household, violence, and incarceration of a household member (Felitti et al., 1998).

长期以来，研究表明童年创伤和逆境与成人负面健康结果之间存在显著关联。这些被称为“童年不良经历或事件”（ACE），包括18岁前儿童所经历的创伤性事件和不安全环境，如虐待、忽视、家庭暴力等。这些经历通过ACE问卷等工具进行评估，并对个体的长期健康产生深远影响。

本文研究了不良童年经历（Adverse Childhood Experiences or Events，ACEs）与基因型-环境交互作用对体重指数（BMI）的影响。研究者使用了Healthy Nevada Project (HNP)的数据，该项目包括43,000名具有全外显子测序（WES）及匹配的电子健康记录的参与者。其中，17,839名参与者提供了关于ACEs的调查结果。研究发现，ACEs次数与成年肥胖具有很强的关联性，并鉴定了55个具有基因交互作用的常见和罕见变异。

图2

在该项研究中，研究者首先研究了ACEs与BMI之间的关联性；然后使用约500万个常见和罕见变异探索了BMI与ACEs的全基因组-环境交互作用。全基因组-环境交互研究（GWEIS）检查了每个变异的基因型-环境（G×E）效应，使得在ACEs暴露下，不同基因型的参与者在BMI上的差异。

测序流程

图3 测序分析

测序数据分析部分，测序reads使用Sentieon进行从fastq到vcf的全流程处理。Sentieon遵循了测序数据相关质控结果统计及GATK最佳实践流程。Sentieon在处理大规模队列样本时，在具有极速分析优势的同时保证了分析结果的可靠性。

Sentieon软件团队拥有丰富的软件开发及算法优化工程经验，致力于解决生物数据分析中的速度与准确度瓶颈，为来自于分子诊断、药物研发、临床医疗、人群队列、动植物等多个领域的合作伙伴提供高效精准的软件解决方案，共同推动基因技术的发展。

截至2023年3月份，Sentieon已经在全球范围内为1300+用户提供服务，被世界一级影响因子刊物如NEJM、Cell、Nature等广泛引用，引用次数超过700篇。此外，Sentieon连续数年摘得了Precision FDA、Dream Challenges等多个权威评比的桂冠，在业内获得广泛认可。

文献结论

图4 文献结论（部分）

This unique examination highlights several of the interactive effects between genetics and behavioral life experiences, and the consequences thereof on population health. Particularly, this study shows that the largely preventable negative health impacts of ACEs modulate purely genetic associations to an often detrimental effect on health. Simply stated, poor health outcomes result from lifestyle-driven events, and these health outcomes increase notably with specific genetic mutations. Conversely, a number of variants have already been shown to play a strong role in the increase of unhealthy BMI levels; when considered in tandem with environmental events such as ACEs, these effects can multiply in strength, resulting in a much worse state of disease. Thus, future emphasis in large population health studies must be placed on the strongly negative impact of adverse events encountered in childhood and the interactive effects of these events with specific genetic variations. Considering a patient’s social environment such as adverse experiences in childhood will provide a more complete clinical arsenal for overall better patient health.