臀围与冠心病的因果推断——孟德尔随机化分析

目的采用孟德尔随机化方法探索调整体质指数的臀围与冠心病患病风险的因果关系。方法利用大样本全基因组关联研究数据,从人体测量特征基因研究(GIANT)数据库(211114名欧洲人)中筛选出与臀围密切相关且相互独立的遗传位点,进而在冠心病全基因重复验证与Meta分析合作组(CARDIoGRAM)数据库(86995名欧洲人)中选出对应的遗传位点,确定工具变量,通过逆方差加权法的两样本孟德尔随机化方法,以OR值反映臀围与冠心病的因果关系。结果共筛选出70个单核苷酸多态性(SNP)作为工具变量,逆方差加权法结果表明,臀围每增加1倍标准差,冠心病的风险降低16.9%(OR=0.831,95%CI 0.730~0.946);MR-Egger回归截距表明遗传多效性不会对结果造成偏倚(截距为-0.0012,P=0.875);"leave-one-out"分析未发现非特异性SNP。结论臀围增加会降低冠心病的患病风险。

Evaluating the causal relationship between hip circumference and coronary heart disease:a Mendelian randomization study

OBJECTIVE To test the causal effect of hip circumference adjusted for body mass index(HCadjBMI)and coronary heart disease(CHD)using a Mendelian randomization analysis.METHODS Based on genome-wide association study,the associations between the genetic instruments(IVs)and HCadjBMI were obtained from the GIANT consortium(n=211114,European),the associations between IVs and CHD were derided from CARDIoGRAM consortium(n=86995,European).The inverse-variance weighted method was used to estimate a pooled OR for the effect of a 1 cm higher HCadjBMI on CHD.Evidence of directional pleiotropy averaged across all variants was sought using MR-Egger regression.RESULTS A total of 70 genetic variants that reached genome-wide significance and independent of each other were identified as IVs.A combined genetic variants expected to confer a lifetime exposure of per SD higher HCadjBMI was associated with a lower risk of CHD(OR=0.831,95%CI 0.730-0.946).MR-Egger regression intercept suggested that directional pleiotropy was unlikely to be biasing the result(intercept-0.0012,P=0.875).There was no specific single nucleotide polymorphism(SNP)detected by"leave one out"analysis.CONCLUSION A genetic predisposition to higher HCadjBMI was associated with lower risk of CHD.