A genome-wide association study for highly sensitive cardiac troponin T levels identified a novel genetic variation near a RBAK-ZNF890P locus in the Japanese general population
A genome-wide association study for highly sensitive cardiac troponin T levels identified a novel genetic variation near a RBAK-ZNF890P locus in the Japanese general population
复制标题
一项针对高度敏感的心肌肌钙蛋白 T 水平的全基因组关联研究在日本普通人群中发现了 RBAK-ZNF890P 基因座附近的一种新的遗传变异
DOI：
10.1016/j.ijcard.2020.12.019
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Sasaki M.
中科院分区：
文献类型：
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作者：
Nasu T;Satoh M;Hachiya T;Sutoh Y;Ohmomo H;Hitomi S;Taguchi S;Kikuchi H;Kobayashi T;Takahashi Y;Osaki T;Morino Y;Sobue K;Shimizu A;Sasaki M.
背景心血管疾病(CVD)是世界范围内导致死亡的主要原因。高敏感性心肌肌钙蛋白T(hs-cTnT)由于心肌细胞损伤而释放到血流中，与心血管疾病的高风险相关。这项研究旨在调查hs-cTnT相关的遗传变异，并检验这是否是日本普通人群中心血管疾病的相关危险因素。方法这是一项基于2013年东北医学巨库计划社区研究的队列的全基因组关联研究。使用具有914,035个常染色体单核苷酸多态的HumanOmniExpressExome珠芯片阵列进行GWAS。应用Framingham风险评分和Suita评分对CVD的未来风险进行评估。结果GWA10个基因座在发现队列中达到提示意义。复制分析证实，10个基因座中的一个rs7798496与hs-cTnT水平升高有关。在发现和复制队列中，rs7798496和hs-cTnT水平之间的关联的组合P值为3.4x 10−8，这表明新的变体达到了基因组范围的意义。Rs7798496位于视网膜母细胞瘤基因产物(RB)相关的Krüppell相关框(KRAB)锌指、锌指蛋白890和假基因(ZNF890P)之间的基因间隔区。Logistic回归分析显示，rs7798496T等位基因的存在与心血管疾病的高风险密切相关。结论本研究揭示了rs7798269的T等位基因与日本普通人群中升高的hs-cTnT水平之间的关联。
BackgroundCardiovascular disease (CVD) is a major cause of mortality worldwide. High-sensitivity cardiac troponin T (hs-cTnT) is released into the bloodstream due to cardiomyocyte damage and is associated with a high CVD risk. This study aimed to investigate hs-cTnT-related genetic variation and to examine whether this is an associated risk factor for CVD in the Japanese general population.MethodsThis was a genome-wide association study (GWAS) based on a cohort from the 2013 Tohoku Medical Megabank Project community study. The GWAS was performed using a HumanOmniExpressExome BeadChip array with 914,035 autosomal single-nucleotide polymorphisms. The Framingham Risk Score and the Suita score were used to evaluate the future risk of CVD.ResultsThe GWAS identified 10 loci reaching suggestive significance in the discovery cohort. A replication analysis confirmed that one of the 10 loci, rs7798496, is associated with elevated hs-cTnT levels. The combinedPvalue in the discovery and replication cohorts for the association between the rs7798496 and hs-cTnT levels was 3.4 × 10−8, which indicates that the novel variant reached genome-wide significance. The rs7798496 loci was located at an intergenic region between the retinoblastoma gene product (RB)-associated Krüppell-associated box (KRAB) zinc finger, zinc finger protein 890, and pseudogene (ZNF890P). Logistic regression analysis revealed that the presence of the rs7798496 T allele was strongly associated with a high risk for CVD.ConclusionsThis study provides insights into a link between a novel genetic variant, T allele of rs7798269, and elevated hs-cTnT levels as a future risk for CVD in the general Japanese population.