Genome-Wide Analysis of Left Ventricular Image-Derived Phenotypes Identifies Fourteen Loci Associated With Cardiac Morphogenesis and Heart Failure Development
Genome-Wide Analysis of Left Ventricular Image-Derived Phenotypes Identifies Fourteen Loci Associated With Cardiac Morphogenesis and Heart Failure Development
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DOI：
10.1161/circulationaha.119.041161
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发表时间：
2019-10-15
期刊：
影响因子：
37.8
通讯作者：
Petersen, Steffen E.
中科院分区：
文献类型：
--
作者：
Aung, Nay;Vargas, Jose D.;Petersen, Steffen E.
背景资料：左心室（LV）图像衍生表型的遗传基础，在心血管疾病的诊断，管理和危险分层中起着至关重要的作用，目前尚不清楚。方法：左室参数的测量来自英国生物库的心血管磁共振研究。基因分型是使用Affyssin阵列进行的，并通过插补进行增强。我们对6个左心室特征-左心室舒张末期容积、左心室收缩末期容积、左心室每搏输出量、左心室射血分数、左心室质量和左心室质量与舒张末期容积比进行了全基因组关联研究。在梅萨研究（动脉粥样硬化多种族研究）中进行了重复分析。我们在广泛的生物信息学分析的基础上确定了全基因组显著位点的候选基因。根据LV全基因组关联研究的汇总统计量构建多基因风险评分，以预测心力衰竭事件。结果如下：该研究包括16923名欧洲英国生物样本库参与者（平均年龄62.5岁; 45.8%为男性），无心肌梗死或心力衰竭。我们发现了14个全基因组显著性位点（左心室舒张末期容积、左心室收缩末期容积和左心室质量与舒张末期容积比各3个位点;左心室射血分数4个位点，左心室质量1个位点），
Background: The genetic basis of left ventricular (LV) image-derived phenotypes, which play a vital role in the diagnosis, management, and risk stratification of cardiovascular diseases, is unclear at present. Methods: The LV parameters were measured from the cardiovascular magnetic resonance studies of the UK Biobank. Genotyping was done using Affymetrix arrays, augmented by imputation. We performed genome-wide association studies of 6 LV traits-LV end-diastolic volume, LV end-systolic volume, LV stroke volume, LV ejection fraction, LV mass, and LV mass to end-diastolic volume ratio. The replication analysis was performed in the MESA study (Multi-Ethnic Study of Atherosclerosis). We identified the candidate genes at genome-wide significant loci based on the evidence from extensive bioinformatic analyses. Polygenic risk scores were constructed from the summary statistics of LV genome-wide association studies to predict the heart failure events. Results: The study comprised 16 923 European UK Biobank participants (mean age 62.5 years; 45.8% men) without prevalent myocardial infarction or heart failure. We discovered 14 genome-wide significant loci (3 loci each for LV end-diastolic volume, LV end-systolic volume, and LV mass to end-diastolic volume ratio; 4 loci for LV ejection fraction, and 1 locus for LV mass) at a stringent P