中国儿童肥胖的遗传易感性与成年期缺血性心脏病发病风险的研究

Association between genetic predisposition to childhood obesity and the risk of adult ischemic heart disease in China

目的分析儿童肥胖的测量学指标BMI相关基因序列变异与发生缺血性心脏病(IHD)、急性冠心病事件(MCE)的关联。方法利用中国慢性病前瞻性研究中6.9万余名具有全基因组遗传数据的样本,剔除基线时患有冠心病、脑卒中、恶性肿瘤的个体,最终纳入64454人。采用既往全基因组关联研究显著性遗传位点构建儿童BMI遗传风险评分,并根据其五分位数进行分组,最低五分位组为低遗传风险组,最高五分位组为高遗传风险组。采用Cox比例风险回归模型计算儿童BMI的遗传风险评分与IHD、MCE发生风险的关联。结果研究对象平均随访10.7年,期间新发IHD 7073例,MCE 1845例。调整了性别、年龄、地区及前10个遗传主成分后,与低遗传风险组相比,高遗传风险组发生IHD、MCE的HRs值(95%CIs)分别为1.10(1.02~1.18)、1.10(0.95~1.27)。遗传风险评分每增加一个标准差,IHD的发病风险增加4%(2%~6%)(线性趋势P=0.001)。进一步调整基线BMI后,高遗传风险组与低遗传风险组的效应值差异无统计学意义,但遗传风险评分与IHD发病风险间仍具有线性趋势(P=0.019)。结论成年人IHD风险随儿童肥胖遗传易感性的增加而增加,提示儿童肥胖是发生IHD的危险因素。儿童肥胖作为一个容易识别的特征,应定期关注其变化情况,实现成年人IHD的早期干预。

Objective To examine the associations of childhood obesity,assessed by genetic variations of childhood body mass index(BMI),with the risk of adult ischemic heart disease(IHD)and major coronary event(MCE).Methods More than 69000 participants from the China Kadoorie Biobank were genotyped.After excluding those with coronary heart disease,stroke,or cancer at baseline,a total of 64454 participants were included in this study.Based on genome-wide significant single nucleotide polymorphisms(SNPs),childhood BMI genetic risk score were constructed for every participant and divided into quintiles,with the lowest quintile as the low genetic risk group and the highest quintile as the high genetic risk group.Cox proportional hazards regression models were used to estimate the association between genetic predisposition to childhood obesity and the risk of ischemic heart disease.Results During a median of 10.7 years of follow-up,7073 incident cases of IHD and 1845 cases of MCE were documented.After adjusting for sex,age,region,and the first ten genetic principal components,the HRs(95%CIs)for IHD and MCE in the high genetic risk group were 1.10(1.02-1.18)and 1.10(0.95-1.27),compared with the low genetic risk group.IHD risk increased by 4%(2%-6%)for each one standard deviation increase in genetic risk score(trend P=0.001).After further adjustment for baseline BMI,the differences between genetic risk groups were not statistically significant,but there was still a linear trend between genetic risk score and IHD risk(trend P=0.019).Conclusions IHD risk increased with genetic predisposition to childhood obesity,suggesting that childhood obesity is an important risk factor for the development of IHD in China.As an easily identifiable feature,changes of childhood BMI should be monitored regularly to realize early intervention of IHD in adults.