Interplay between demographic, clinical and polygenic risk factors for severe COVID-19.
Interplay between demographic, clinical and polygenic risk factors for severe COVID-19.
复制标题
DOI：
10.1093/ije/dyac137
复制
发表时间：
2022-10-13
影响因子：
7.7
通讯作者：
中科院分区：
文献类型：
--
作者：
我们的目的是确定一般人群中严重 COVID-19（住院、重症监护入院或死亡）的临床、社会人口和遗传风险因素。在这项观察性研究中，我们确定了 2020 年期间诊断出患有 COVID-19 的 9560 名英国生物银行参与者。使用公开的欧洲和跨种族 COVID-19 全基因组摘要统计数据得出并优化了严重 COVID-19 的多基因风险评分 (PRS)。我们估计了 COVID-19 诊断后 28 天内住院或重症监护室入院或 100 天内死亡的风险，并评估了与社会人口因素、免疫抑制剂的使用以及英国生物银行入组（2006-2010 年）和 PRS 中报告的发病率的关联。为了提高生物学理解，使用包含 PRS 的遗传变异进行通路分析。我们纳入了 9560 名患者，自 COVID-19 诊断以来，随访时间中位数为 61 天（四分位数间距 = 34-88）天。患严重 COVID-19 的风险随着年龄和肥胖而增加，男性、当前吸烟者、生活在社会经济贫困地区的人、历史上使用过免疫抑制剂的人以及患有疾病和合并症计数较高的个人的风险更高。优化的 PRS 富含多种免疫相关途径中的单核苷酸多态性，包括“寡腺苷酸合成酶抗病毒反应”和“白细胞介素 10 信号传导”途径，与严重的 COVID-19 相关（调整后的比值比为 1.32，与最低 PRS 五分位相比，最高的比值比为 1.11-1.58）。这项研究是在 SARS-CoV-2 疫苗接种之前进行的，强调了通过使用遗传数据以及普遍考虑的临床和社会人口因素来获得新的见解，以更好地了解严重的 COVID-19 结果的生物学知识。
We aimed to identify clinical, socio-demographic and genetic risk factors for severe COVID-19 (hospitalization, critical care admission or death) in the general population. In this observational study, we identified 9560 UK Biobank participants diagnosed with COVID-19 during 2020. A polygenic risk score (PRS) for severe COVID-19 was derived and optimized using publicly available European and trans-ethnic COVID-19 genome-wide summary statistics. We estimated the risk of hospital or critical care admission within 28 days or death within 100 days following COVID-19 diagnosis, and assessed associations with socio-demographic factors, immunosuppressant use and morbidities reported at UK Biobank enrolment (2006–2010) and the PRS. To improve biological understanding, pathway analysis was performed using genetic variants comprising the PRS. We included 9560 patients followed for a median of 61 (interquartile range = 34–88) days since COVID-19 diagnosis. The risk of severe COVID-19 increased with age and obesity, and was higher in men, current smokers, those living in socio-economically deprived areas, those with historic immunosuppressant use and individuals with morbidities and higher co-morbidity count. An optimized PRS, enriched for single-nucleotide polymorphisms in multiple immune-related pathways, including the ‘oligoadenylate synthetase antiviral response’ and ‘interleukin-10 signalling’ pathways, was associated with severe COVID-19 (adjusted odds ratio 1.32, 95% CI 1.11–1.58 for the highest compared with the lowest PRS quintile). This study conducted in the pre-SARS-CoV-2-vaccination era, emphasizes the novel insights to be gained from using genetic data alongside commonly considered clinical and socio-demographic factors to develop greater biological understanding of severe COVID-19 outcomes.
登录
查看更多内容
增强流行病学观察研究的报告（Strobe）陈述：报告观察性研究的指南。
影响因子：
15.8
作者：
通讯作者：
--
影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
影响因子：
3.7
作者：
Dite GS;Murphy NM;Allman R
通讯作者：
Allman R
影响因子：
64.8
作者：
COVID-19 Host Genetics Initiative
通讯作者：
COVID-19 Host Genetics Initiative
影响因子：
9.2
作者：
Choi, Shing Wan;O'Reilly, Paul F.
通讯作者：
O'Reilly, Paul F.