Genome-Wide Association Study of Absolute QRS Voltage Identifies Common Variants of TBX3 as Genetic Determinants of Left Ventricular Mass in a Healthy Japanese Population.
Genome-Wide Association Study of Absolute QRS Voltage Identifies Common Variants of TBX3 as Genetic Determinants of Left Ventricular Mass in a Healthy Japanese Population.
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DOI：
10.1371/journal.pone.0155550
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Japan Pharmacogenomics Data Science Consortium (JPDSC)
中科院分区：
文献类型：
--
作者：
Sano M;Kamitsuji S;Kamatani N;Tabara Y;Kawaguchi T;Matsuda F;Yamagishi H;Fukuda K;Japan Pharmacogenomics Data Science Consortium (JPDSC)
左心室肥厚（LVH）是导致心力衰竭的常见最终途径。我们在健康的日本人群中使用绝对心电图QRS电压值寻找左心室（LV）质量的遗传决定因素。在调整协变量后，对日本药物基因组学数据科学联盟（JPDSC）数据库中2994名健康志愿者V1和V5导联校正后的S波和R波电压进行全基因组关联研究。潜在的关联通过一项计算机复制研究得到验证，该研究使用的是来自Nagahama综合人类生物科学前瞻性基因组队列的独立日本人群。我们发现了日本人V5导联R波电压与SNP rs7301743之间的新关联[G]，该SNP位于编码T-box转录因子Tbx3的基因附近。对两个独立的日本数据集的荟萃分析显示，TBX3|MED13L中SNP rs7301743与每个小等位基因拷贝的V5导联R波振幅缩短0.071 mV （95% CI, 0.038-0.11 mV）存在边际显著相关（P = 7.635 x 10−8）。转录抑制因子TBX3被认为可以抑制工作心室心肌的发育。我们的研究结果表明，在健康的日本人群中，Tbx3基因变异与左室质量有关。
Left ventricular hypertrophy (LVH) represents a common final pathway leading to heart failure. We have searched for genetic determinants of left ventricular (LV) mass using values for absolute electrocardiographic QRS voltage in a healthy Japanese population. After adjusting for covariates, the corrected S and R wave voltages in leads V1 and V5 from 2,994 healthy volunteers in the Japan Pharmacogenomics Data Science Consortium (JPDSC) database were subjected to a genome-wide association study. Potential associations were validated by an in silico replication study using an independent Japanese population obtained from the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience. We identified a novel association between the lead V5, R wave voltage in Japanese individuals and SNP rs7301743[G], which maps near the gene encoding T-box transcription factor Tbx3. Meta-analysis of two independent Japanese datasets demonstrated a marginally significant association of SNP rs7301743 in TBX3|MED13L with a 0.071 mV (95% CI, 0.038–0.11 mV) shorter R wave amplitude in the V5 lead per minor allele copy (P = 7.635 x 10−8). The transcriptional repressor, TBX3, is proposed to suppress the development of working ventricular myocardium. Our findings suggest that genetic variation of Tbx3 is associated with LV mass in a healthy Japanese population.