Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
Age-dependent impact of the major common genetic risk factor for COVID-19 on severity and mortality
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DOI：
10.1172/jci152386
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发表时间：
2021-12-01
影响因子：
15.9
通讯作者：
Ganna, Andrea
中科院分区：
文献类型：
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作者：
Nakanishi, Tomoko;Pigazzini, Sara;Ganna, Andrea
背景。在年轻人中，COVID-19的结果存在相当大的差异，其中一些差异可能是由于遗传易感性。方法。我们结合来自9个国家17个队列的13888名COVID-19患者（n = 7185名住院患者）的个体水平数据，评估主要常见的COVID-19遗传危险因素（rs10490770标记的3号染色体位点）与死亡率、COVID-19相关并发症和实验室值的关系。接下来，我们使用FinnGen和哥伦比亚大学COVID-19生物银行进行了荟萃分析。结果。我们发现rs10490770风险等位基因携带者的全因死亡风险增加（HR, 1.4; 95% CI, 1.2-1.7）。风险等位基因携带者发生几种COVID-19并发症的几率增加：严重呼吸衰竭（OR, 2.1; 95% CI, 1.6-2.6）、静脉血栓栓塞（OR, 1.7; 95% CI, 1.2-2.4）和肝损伤（OR, 1.5; 95% CI, 1.2-2.0）。与60岁以上（or, 1.5; 95% CI, 1.2-1.8；相互作用，P = 0.038）的患者相比，60岁及以下的风险等位基因携带者死亡或严重呼吸衰竭的几率更高（or, 2.7; 95% CI, 1.8-3.9）。在60岁及以下死亡或经历严重呼吸衰竭的个体中，32.3%是风险变异携带者，而没有经历这些结果的个体中有13.9%是风险变异携带者。这一风险变异改善了死亡或严重呼吸衰竭的预测，与大多数已确定的临床风险因素相似，甚至更好。结论。COVID-19常见的主要遗传风险因素与发病率和死亡率风险增加有关，这在60岁或以下的个体中更为明显。这种影响在程度上与大多数已确定的临床风险因素相似，并且更为常见，这提示了对未来临床风险管理的潜在影响。
BACKGROUND. There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition. METHODS. We combined individual level data from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank. RESULTS. We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors. CONCLUSIONS. The major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.