關(guān)鍵詞：應(yīng)用遺傳流行病學(xué)；群體測序；群體基因組；基因組變異檢測；
文獻(xiàn)簡介
標(biāo)題（英文）：The Impact of ACEs on BMI: An Investigation of the Genotype-Environment Effects of BMI
標(biāo)題（中文）：ACEs對BMI的影響：探究BMI的基因型-環(huán)境效應(yīng)
發(fā)表期刊：Behavior Genetics
作者單位：美國俄勒岡州立大學(xué)心理學(xué)系
發(fā)表年份：2022
文章地址：https://doi.org/10.3389/fgene.2022.816660
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).
長期以來，研究表明童年創(chuàng)傷和逆境與成人負(fù)面健康結(jié)果之間存在顯著關(guān)聯(lián)。這些被稱為“童年不良經(jīng)歷或事件”（ACE），包括18歲前兒童所經(jīng)歷的創(chuàng)傷性事件和不安全環(huán)境，如虐待、忽視、家庭暴力等。這些經(jīng)歷通過ACE問卷等工具進(jìn)行評估，并對個體的長期健康產(chǎn)生深遠(yuǎn)影響。
本文研究了不良童年經(jīng)歷（Adverse Childhood Experiences or Events，ACEs）與基因型-環(huán)境交互作用對體重指數(shù)（BMI）的影響。研究者使用了Healthy Nevada Project (HNP)的數(shù)據(jù)，該項目包括43,000名具有全外顯子測序（WES）及匹配的電子健康記錄的參與者。其中，17,839名參與者提供了關(guān)于ACEs的調(diào)查結(jié)果。研究發(fā)現(xiàn)，ACEs次數(shù)與成年肥胖具有很強的關(guān)聯(lián)性，并鑒定了55個具有基因交互作用的常見和罕見變異。
在該項研究中，研究者首先研究了ACEs與BMI之間的關(guān)聯(lián)性；然后使用約500萬個常見和罕見變異探索了BMI與ACEs的全基因組-環(huán)境交互作用。全基因組-環(huán)境交互研究（GWEIS）檢查了每個變異的基因型-環(huán)境（G×E）效應(yīng)，使得在ACEs暴露下，不同基因型的參與者在BMI上的差異。
測序流程
測序數(shù)據(jù)分析部分，測序reads使用Sentieon進(jìn)行從fastq到vcf的全流程處理。Sentieon遵循了測序數(shù)據(jù)相關(guān)質(zhì)控結(jié)果統(tǒng)計及GATK最佳實踐流程。Sentieon在處理大規(guī)模隊列樣本時，在具有極速分析優(yōu)勢的同時保證了分析結(jié)果的可靠性。
Sentieon軟件團(tuán)隊擁有豐富的軟件開發(fā)及算法優(yōu)化工程經(jīng)驗，致力于解決生物數(shù)據(jù)分析中的速度與準(zhǔn)確度瓶頸，為來自于分子診斷、藥物研發(fā)、臨床醫(yī)療、人群隊列、動植物等多個領(lǐng)域的合作伙伴提供高效精準(zhǔn)的軟件解決方案，共同推動基因技術(shù)的發(fā)展。
截至2023年3月份，Sentieon已經(jīng)在全球范圍內(nèi)為1300+用戶提供服務(wù)，被世界一級影響因子刊物如NEJM、Cell、Nature等廣泛引用，引用次數(shù)超過700篇。此外，Sentieon連續(xù)數(shù)年摘得了Precision FDA、Dream Challenges等多個權(quán)威評比的桂冠，在業(yè)內(nèi)獲得廣泛認(rèn)可。
文獻(xiàn)結(jié)論
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.
總結(jié)
該研究使用了包括全外顯子測序（Sentieon用于全流程數(shù)據(jù)分析）、電子健康記錄、ACEs調(diào)查結(jié)果及全基因組-環(huán)境交互研究（GWEIS）等方法探索了ACEs、遺傳因素和BMI之間的關(guān)系。
