中国成年人生活方式和心血管代谢因素与甲基化年龄加速的相关性分析  

Association of lifestyle and cardiometabolic risk factors with epigenetic age acceleration in adults in China

作　　者：陈璐 司佳卉 孙点剑一 余灿清[1,2] 郭彧 裴培[4] 陈君石 陈铮鸣[6] 吕筠[1,2,7] 李立明 Chen Lu;Si Jiahui;Sun Dianjianyi;Yu Canqing;Guo Yu;Pei Pei;Chen Junshi;Chen Zhengming;Lyu Jun;Li Liming(Department of Epidemiology and Biostatistics,School of Public Health,Peking University,Beijing 100191,China;Peking University Center for Public Health and Epidemic Preparedness&Response,Beijing 100191,China;Fuwai Hospital,Chinese Academy of Medical Sciences,National Center for Cardiovascular Diseases,Beijing 100037,China;Chinese Academy of Medical Sciences,Beijing 100730,China;China National Center for Food Safety Risk Assessment,Beijing 100022,China;Clinical Trial Service Unit and Epidemiological Studies Unit,Nuffield Department of Population Health,University of Oxford,Oxford OX37LF,UK;Key Laboratory of Molecular Cardiovascular Sciences(Peking University),Ministry of Education,Beijing 100191,China)

机构地区：[1]北京大学公共卫生学院流行病与卫生统计学系,北京100191 [2]北京大学公众健康与重大疫情防控战略研究中心,北京100191 [3]中国医学科学院阜外医院,国家心血管疾病中心,北京100037 [4]中国医学科学院,北京100730 [5]国家食品安全风险评估中心,北京100022 [6]英国牛津大学临床与流行病学研究中心纳菲尔德人群健康系,英国OX37LF [7]北京大学分子心血管学教育部重点实验室,北京100191

出　　处：《中华流行病学杂志》2022年第7期1019-1029,共11页Chinese Journal of Epidemiology

基　　金：国家自然科学基金(81941018);国家重点研发计划(2016YFC0900500);中国香港Kadoorie Charitable基金;英国Wellcome Trust(212946/Z/18/Z,202922/Z/16/Z,104085/Z/14/Z,088158/Z/09/Z)。

摘　　要：目的:比较分析5种甲基化年龄加速指标与生活方式和心血管代谢因素间的相关性。方法:基于中国慢性病前瞻性研究中有基线外周血全基因组甲基化检测数据的研究对象980人,计算Horvath时钟、Hannum时钟、DNAm PhenoAge、GrimAge和Li时钟5种甲基化年龄。根据甲基化年龄对实足年龄回归的残差值计算甲基化年龄加速。研究的生活方式因素包括吸烟、饮酒、饮食习惯、体力活动、经BMI和腰围联合定义的体型。心血管代谢因素包括血压、血糖和TC。利用一般线性模型分析生活方式和心血管代谢因素与各甲基化年龄加速指标的相关性[β值(95%CI)]。结果:GrimAge加速指标与吸烟、饮酒、体力活动水平及BMI存在关联。与不吸烟、不饮酒或BMI为18.5~23.9 kg/m 2者相比,吸烟者(每天吸烟1~14、15~24、≥25支者对应的β值依次为0.71(95%CI:0.57~0.86)、0.88(95%CI:0.73~1.03)、0.99(95%CI:0.81~1.18)、重度饮酒者[每日纯乙醇量≥60 g:0.33(95%CI:0.11~0.55)]、BMI<18.5 kg/m 2者[0.23(95%CI:0.03~0.43)]表现为加速衰老;与体力活动水平低者相比,中、较高、高体力活动者表现为减速衰老[β值依次为-0.14(95%CI:-0.27~-0.00)、-0.12(95%CI:-0.26~0.02)、-0.13(95%CI:-0.26~0.01)]。随着健康生活方式数量的增加,GrimAge加速指标呈现下降趋势(P<0.001);与具有0~1个健康生活方式者相比,具有2、3、或4~5个健康生活方式者的β值依次为-0.30(95%CI:-0.47~-0.12)、-0.47(95%CI:-0.65~-0.30)、-0.72(95%CI:-0.90~-0.53)。其他4个指标与多数生活方式因素不存在有统计学显著性的关联。5种甲基化年龄加速指标与血压、血糖和TC均不存在关联。结论:生活方式不健康者表现出表观遗传年龄的加速,即DNA甲基化预测年龄老于实足年龄。Objective To explore the association of lifestyle and cardiometabolic risk factors with five epigenetic age acceleration(AA)indices.Methods This study included 980 participants of China Kadoorie Biobank,for whom genome-wide DNA methylation of peripheral blood cells had been detected in baseline survey.Five indices of DNA methylation age(DNAm age)were calculated,i.e.Horvath clock,Hannum clock,DNAm PhenoAge,GrimAge and Li clock.Epigenetic AA was defined as the residual of regressing DNAm age on chronological age.Lifestyle factors studied included smoking status,alcohol consumption,eating habits,physical activity level and body shape defined by a combination of BMI and waist circumference.Cardiometabolic risk factors included blood pressure,blood glucose level and total cholesterol level.Linear regression model was used to analyze the association of lifestyle and cardiometabolic risk factors with AA(β).Results GrimAge_AA was associated with smoking status,alcohol consumption,physical activity level and BMI.Compared with non-smokers,non-drinkers,or participants with BMI of 18.5-23.9 kg/m2,the smokers who smoked 1-14 cigarettes/day(β=0.71,95%CI:0.57-0.86),15-24 cigarettes/day(β=0.88,95%CI:0.73-1.03),and≥25 cigarettes/day(β=0.99,95%CI:0.81-1.18),respectively,heavy drinkers with daily pure alcohol consumption≥60 g(β=0.33,95%CI:0.11-0.55)and participants with BMI<18.5 kg/m2(β=0.23,95%CI:0.03-0.43)showed accelerated aging.Compared with those in the lowest quintile of physical activity level,participants in the top three quintile of physical activity level showed decelerated aging(β=-0.13,95%CI:-0.26-0.01,β=-0.12,95%CI:-0.26-0.02,andβ=-0.14,95%CI:-0.27--0.00,respectively).GrimAge_AA decreased with the increase of the number of healthy lifestyle factors(P<0.001).Compared with the participants with 0 to 1 healthy lifestyle factor,theβof those with 2,3,or 4 to 5 healthy lifestyle factors were-0.30(95%CI:-0.47--0.12),-0.47(95%CI:-0.65--0.30)and-0.72(95%CI:-0.90--0.53),respectively.The other four indices were not

关 键 词：甲基化年龄加速 生活方式 心血管代谢性因素 

分 类 号：R195[医药卫生—卫生统计学]