Genetic predisposition may not improve prediction of cardiac surgery-associated acute kidney injury.
Genetic predisposition may not improve prediction of cardiac surgery-associated acute kidney injury.
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DOI：
10.3389/fgene.2023.1094908
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发表时间：
2023
影响因子：
3.7
通讯作者：
Kertai, Miklos D.
中科院分区：
文献类型：
--
作者：
Douville, Nicholas J.;Larach, Daniel B.;Lewis, Adam;Bastarache, Lisa;Pandit, Anita;He, Jing;Heung, Michael;Mathis, Michael;Wanderer, Jonathan P.;Kheterpal, Sachin;Surakka, Ida;Kertai, Miklos D.
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背景资料：最近基因组数据与电子健康记录的整合使得对各种围手术期并发症的大规模基因组研究成为可能，但对急性肾损伤的全基因组关联研究在规模上受到限制或受到复合结局的混淆。全基因组关联研究可以用来创建多基因风险评分，然后将其与传统的临床风险因素相结合，以更好地预测术后并发症，如急性肾损伤。 研究方法：利用来自两个学术生物库的综合遗传数据，我们对心脏手术相关的急性肾损伤进行了全基因组关联研究。接下来，我们开发了一个多基因风险评分，并在控制年龄、性别、主成分、术前血清肌酐以及一系列患者、临床和手术风险因素的回归中测试预测效用。最后，我们使用遗传混合模型估计加性变异遗传力。 结果如下：在范德比尔特大学医学中心的1,014例合格手术和密歇根医学中心的478例合格手术中，分别有348例（34.3%）和121例（25.3%）发生了阿基。没有变异超过全基因组显著性（p < 5 × 10−8）阈值，然而，6个以前未报告的变异超过了提示阈值（p < 1 × 10−6）。检测到的显著变体包括：1）rs74637005，位于NFU 1的外显子区域; 2）rs 17438465，位于EVX 1和HIBADH之间。我们未能从先前的术后急性肾损伤无偏倚研究中复制出变异体。在任何模型中，多基因风险与术后急性肾损伤均无显著相关性，然而，（aOR = 1.002，95% CI 1.000-1.003，p = 0.013），糖尿病在全模型中，心血管疾病（aOR = 2.025，95% CI 1.320-3.103，p = 0.001）和瓣膜疾病（aOR = 0.558，95% CI 0.372-0.835，p = 0.005）具有显著性。 结论：多基因风险评分与心脏手术相关的急性肾损伤无显著相关性，急性肾损伤在该人群中可能具有较低的遗传力。这些结果表明，易感性仅受基线遗传易感性的影响最小，并且临床风险因素（其中一些是可改变的）可能在预测这种并发症中发挥更大的影响作用。与临床风险因素相比，遗传学对心脏手术相关急性肾损伤总体风险的总体影响可能很小。
Background: The recent integration of genomic data with electronic health records has enabled large scale genomic studies on a variety of perioperative complications, yet genome-wide association studies on acute kidney injury have been limited in size or confounded by composite outcomes. Genome-wide association studies can be leveraged to create a polygenic risk score which can then be integrated with traditional clinical risk factors to better predict postoperative complications, like acute kidney injury. Methods: Using integrated genetic data from two academic biorepositories, we conduct a genome-wide association study on cardiac surgery-associated acute kidney injury. Next, we develop a polygenic risk score and test the predictive utility within regressions controlling for age, gender, principal components, preoperative serum creatinine, and a range of patient, clinical, and procedural risk factors. Finally, we estimate additive variant heritability using genetic mixed models. Results: Among 1,014 qualifying procedures at Vanderbilt University Medical Center and 478 at Michigan Medicine, 348 (34.3%) and 121 (25.3%) developed AKI, respectively. No variants exceeded genome-wide significance (p < 5 × 10−8) threshold, however, six previously unreported variants exceeded the suggestive threshold (p < 1 × 10−6). Notable variants detected include: 1) rs74637005, located in the exonic region of NFU1 and 2) rs17438465, located between EVX1 and HIBADH. We failed to replicate variants from prior unbiased studies of post-surgical acute kidney injury. Polygenic risk was not significantly associated with post-surgical acute kidney injury in any of the models, however, case duration (aOR = 1.002, 95% CI 1.000–1.003, p = 0.013), diabetes mellitus (aOR = 2.025, 95% CI 1.320–3.103, p = 0.001), and valvular disease (aOR = 0.558, 95% CI 0.372–0.835, p = 0.005) were significant in the full model. Conclusion: Polygenic risk score was not significantly associated with cardiac surgery-associated acute kidney injury and acute kidney injury may have a low heritability in this population. These results suggest that susceptibility is only minimally influenced by baseline genetic predisposition and that clinical risk factors, some of which are modifiable, may play a more influential role in predicting this complication. The overall impact of genetics in overall risk for cardiac surgery-associated acute kidney injury may be small compared to clinical risk factors.
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影响因子：
3.6
作者：
Zivotic, Maja;Dundjerovic, Dusko;Naumovic, Radomir;Kovacevic, Sanjin;Ivanov, Milan;Karanovic, Danijela;Nikolic, Gorana;Markovic-Lipkovski, Jasmina;Skodric, Sanja Radojevic;Ostojic, Jelena Nesovic
通讯作者：
Ostojic, Jelena Nesovic
影响因子：
2.1
作者：
Dudbridge F
通讯作者：
Dudbridge F
DOI：
10.1161/circgen.120.003269
发表时间：
2021-04
期刊：
Circulation. Genomic and precision medicine
影响因子：
--
作者：
Kertai MD;Mosley JD;He J;Ramakrishnan A;Abdelmalak MJ;Hong Y;Shoemaker MB;Roden DM;Bastarache L
通讯作者：
Bastarache L
影响因子：
3
作者：
Elixhauser, A;Steiner, C;Coffey, RN
通讯作者：
Coffey, RN
影响因子：
9.8
作者：
Douville, Nicholas J.;Kheterpal, Sachin;Douville, Christopher B.
通讯作者：
Douville, Christopher B.