Department of Biostatistics, Yale University, New Haven, Connecticut, USA.
Genet Epidemiol. 2023 Apr;47(3):215-230. doi: 10.1002/gepi.22515. Epub 2023 Jan 24.
Analysis of host genetic components provides insights into the susceptibility and response to viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). To reveal genetic determinants of susceptibility to COVID-19 related mortality, we train a deep learning model to identify groups of genetic variants and their interactions that contribute to the COVID-19 related mortality risk using the UK Biobank data (28,097 affected cases and 1656 deaths). We refer to such groups of variants as super variants. We identify 15 super variants with various levels of significance as susceptibility loci for COVID-19 mortality. Specifically, we identify a super variant (odds ratio [OR] = 1.594, p = 5.47 × 10 ) on Chromosome 7 that consists of the minor allele of rs76398985, rs6943608, rs2052130, 7:150989011_CT_C, rs118033050, and rs12540488. We also discover a super variant (OR = 1.353, p = 2.87 × 10 ) on Chromosome 5 that contains rs12517344, rs72733036, rs190052994, rs34723029, rs72734818, 5:9305797_GTA_G, and rs180899355.
分析宿主遗传成分可以深入了解易感性和对病毒感染的反应，例如严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2），它会引起 2019 年冠状病毒病（COVID-19）。为了揭示与 COVID-19 相关死亡率相关的遗传决定因素，我们使用英国生物银行数据（28097 例受影响病例和 1656 例死亡），训练一个深度学习模型来识别导致 COVID-19 相关死亡率风险的遗传变异组及其相互作用。我们将此类变异组称为超级变异体。我们确定了 15 个具有不同显著水平的超级变体，作为 COVID-19 死亡率的易感性基因座。具体来说，我们确定了一个超级变体（优势比[OR] = 1.594，p = 5.47 × 10 ）位于 7 号染色体上，由 rs76398985、rs6943608、rs2052130、7:150989011_CT_C、rs118033050 和 rs12540488 的次要等位基因组成。我们还在 5 号染色体上发现了一个超级变体（OR = 1.353，p = 2.87 × 10 ），其中包含 rs12517344、rs72733036、rs190052994、rs34723029、rs72734818、5:9305797_GTA_G 和 rs180899355。
