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成人身高、冠心病和中风:多基因座孟德尔随机化荟萃分析

Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis.

作者信息

Nüesch Eveline, Dale Caroline, Palmer Tom M, White Jon, Keating Brendan J, van Iperen Erik Pa, Goel Anuj, Padmanabhan Sandosh, Asselbergs Folkert W, Verschuren W M, Wijmenga C, Van der Schouw Y T, Onland-Moret N C, Lange Leslie A, Hovingh G K, Sivapalaratnam Suthesh, Morris Richard W, Whincup Peter H, Wannamethe Goya S, Gaunt Tom R, Ebrahim Shah, Steel Laura, Nair Nikhil, Reiner Alexander P, Kooperberg Charles, Wilson James F, Bolton Jennifer L, McLachlan Stela, Price Jacqueline F, Strachan Mark Wj, Robertson Christine M, Kleber Marcus E, Delgado Graciela, März Winfried, Melander Olle, Dominiczak Anna F, Farrall Martin, Watkins Hugh, Leusink Maarten, Maitland-van der Zee Anke H, de Groot Mark Ch, Dudbridge Frank, Hingorani Aroon, Ben-Shlomo Yoav, Lawlor Debbie A, Amuzu A, Caufield M, Cavadino A, Cooper J, Davies T L, Drenos F, Engmann J, Finan C, Giambartolomei C, Hardy R, Humphries S E, Hypponen E, Kivimaki M, Kuh D, Kumari M, Ong K, Plagnol V, Power C, Richards M, Shah S, Shah T, Sofat R, Talmud P J, Wareham N, Warren H, Whittaker J C, Wong A, Zabaneh D, Davey Smith George, Wells Jonathan C, Leon David A, Holmes Michael V, Casas Juan P

机构信息

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

CTU Bern, Department of Clinical Research and Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland.

出版信息

Int J Epidemiol. 2016 Dec 1;45(6):1927-1937. doi: 10.1093/ije/dyv074.

Abstract

BACKGROUND

We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis.

METHODS

We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D.

RESULTS

IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index ( P  < 0.001), triglycerides ( P  < 0.001), non high-density (non-HDL) cholesterol ( P  < 0.001), C-reactive protein ( P  = 0.042), and systolic blood pressure ( P  = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity ( P  < 0.001 for both).

CONCLUSIONS

Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure.

摘要

背景

我们采用工具变量(IV)孟德尔随机化荟萃分析,研究了以成人身高衡量的完整生长对冠心病(CHD)、中风和心血管特征的因果效应。

方法

我们基于与成人身高相关的69个单核苷酸多态性(SNP)开发了一个等位基因评分,这些SNP由IBCCardioChip鉴定,并将其用于对21项研究中的60028名参与者的心血管危险因素和事件进行IV分析。对冠心病的IV分析由来自GIANT联盟的180个身高SNP及其从CARDIoGRAMplusC4D得出的相应冠心病估计值的汇总数据进行补充。

结果

来自IBCCardioChip和GIANT - CARDIoGRAMplusC4D的IV估计表明,身高增加6.5厘米可使冠心病几率降低10%[优势比分别为0.90;95%置信区间(CI):0.78至1.03和0.85至0.95],这与新兴危险因素协作组的估计结果一致(风险比0.93;95%CI:0.91至0.94)。IV分析显示与中风无关联(优势比0.97;95%CI:0.79至1.19)。IV分析表明,身高增加6.5厘米会导致体重指数(P<0.001)、甘油三酯(P<0.001)、非高密度(非HDL)胆固醇(P<0.001)、C反应蛋白(P = 0.042)和收缩压(P = 0.064)水平降低,以及1秒用力呼气量和用力肺活量水平升高(两者P均<0.001)。

结论

较高的个体患冠心病的风险较低,可能的解释是较高的人肺功能更好,体重指数、胆固醇和血压水平较低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb8/5841831/d7c8e5415908/dyv074f1.jpg

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