Genetically determined height and coronary artery disease.
Genetically determined height and coronary artery disease.
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DOI：
10.1056/nejmoa1404881
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发表时间：
2015-04-23
期刊：
影响因子：
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通讯作者：
CARDIoGRAM+C4D Consortium
中科院分区：
文献类型：
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作者：
Nelson CP;Hamby SE;Saleheen D;Hopewell JC;Zeng L;Assimes TL;Kanoni S;Willenborg C;Burgess S;Amouyel P;Anand S;Blankenberg S;Boehm BO;Clarke RJ;Collins R;Dedoussis G;Farrall M;Franks PW;Groop L;Hall AS;Hamsten A;Hengstenberg C;Hovingh GK;Ingelsson E;Kathiresan S;Kee F;König IR;Kooner J;Lehtimäki T;März W;McPherson R;Metspalu A;Nieminen MS;O'Donnell CJ;Palmer CN;Peters A;Perola M;Reilly MP;Ripatti S;Roberts R;Salomaa V;Shah SH;Schreiber S;Siegbahn A;Thorsteinsdottir U;Veronesi G;Wareham N;Willer CJ;Zalloua PA;Erdmann J;Deloukas P;Watkins H;Schunkert H;Danesh J;Thompson JR;Samani NJ;CARDIoGRAM+C4D Consortium
成人身高与冠状动脉疾病（CAD）风险之间负相关的性质和潜在机制尚不清楚。我们使用遗传学方法来研究身高和CAD之间的关联，使用180个身高相关的遗传变异。我们在65，066例病例和128，383例对照中检测了遗传决定的身高变化1 SD（6.5 cm）与CAD风险之间的关系。使用来自18，249人的个体水平基因型数据，我们还检查了与不同数量的身高相关等位基因存在相关的CAD风险。为了确定假定的机制，我们分析了遗传决定的身高是否与已知的心血管危险因素相关，并对身高相关基因进行了途径分析。我们观察到遗传决定的身高每降低1个标准差，CAD风险相对增加13.5%（95%置信区间[CI]，5.4 ~ 22.1; P<0.001）。身高增高变异数量增加与CAD风险降低之间存在分级关系（身高四分位数4与四分位数1的比值比为0.74; 95%CI为0.68 - 0.84; P<0.001）。在我们研究的12个风险因素中，我们观察到仅与低密度脂蛋白胆固醇和甘油三酯水平显著相关（约占相关性的30%）。我们确定了几个重叠的途径，涉及与发育和动脉粥样硬化相关的基因。遗传决定的较矮身高与CAD风险增加之间存在主要关联，这种关联部分可以通过较矮身高与不良血脂之间的关联来解释。决定身高和动脉粥样硬化发展的共同生物学过程可能解释了一些相关性。
The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association.