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Genome-wide analysis in 756,646 individuals provides first genetic evidence that ACE2 expression influences COVID-19 risk and yields genetic risk scores predictive of severe disease
medRxiv - Genetic and Genomic Medicine Pub Date : 2021-06-10 , DOI: 10.1101/2020.12.14.20248176 J E Horowitz 1 , J A Kosmicki 1 , A Damask 1 , D Sharma 1 , G H L Roberts 2 , A E Justice 3 , N Banerjee 1 , M V Coignet 2 , A Yadav 1 , J B Leader 3 , A Marcketta 1 , D S Park 2 , R Lanche 1 , E Maxwell 1 , S C Knight 2 , X Bai 1 , H Guturu 2 , D Sun 1 , A Baltzell 2 , F S P Kury 1 , J D Backman 1 , A R Girshick 2 , C O'Dushlaine 1 , S R McCurdy 2 , R Partha 2 , A J Mansfield 1 , D A Turissini 2 , A H Li 1 , M Zhang 2 , J Mbatchou 1 , K Watanabe 1 , L Gurski 1 , S E McCarthy 1 , H M Kang 1 , L Dobbyn 1 , E Stahl 1 , A Verma 4 , G Sirugo 4 , , M D Ritchie 4 , M Jones 1 , S Balasubramanian 1 , K Siminovitch 1 , W J Salerno 1 , A R Shuldiner 1 , D J Rader 4 , T Mirshahi 3 , A E Locke 1 , J Marchini 1 , J D Overton 1 , D J Carey 3 , L Habegger 1 , M N Cantor 1 , K A Rand 2 , E L Hong 2 , J G Reid 1 , C A Ball 2 , A Baras 1 , G R Abecasis 1 , M A Ferreira 1
medRxiv - Genetic and Genomic Medicine Pub Date : 2021-06-10 , DOI: 10.1101/2020.12.14.20248176 J E Horowitz 1 , J A Kosmicki 1 , A Damask 1 , D Sharma 1 , G H L Roberts 2 , A E Justice 3 , N Banerjee 1 , M V Coignet 2 , A Yadav 1 , J B Leader 3 , A Marcketta 1 , D S Park 2 , R Lanche 1 , E Maxwell 1 , S C Knight 2 , X Bai 1 , H Guturu 2 , D Sun 1 , A Baltzell 2 , F S P Kury 1 , J D Backman 1 , A R Girshick 2 , C O'Dushlaine 1 , S R McCurdy 2 , R Partha 2 , A J Mansfield 1 , D A Turissini 2 , A H Li 1 , M Zhang 2 , J Mbatchou 1 , K Watanabe 1 , L Gurski 1 , S E McCarthy 1 , H M Kang 1 , L Dobbyn 1 , E Stahl 1 , A Verma 4 , G Sirugo 4 , , M D Ritchie 4 , M Jones 1 , S Balasubramanian 1 , K Siminovitch 1 , W J Salerno 1 , A R Shuldiner 1 , D J Rader 4 , T Mirshahi 3 , A E Locke 1 , J Marchini 1 , J D Overton 1 , D J Carey 3 , L Habegger 1 , M N Cantor 1 , K A Rand 2 , E L Hong 2 , J G Reid 1 , C A Ball 2 , A Baras 1 , G R Abecasis 1 , M A Ferreira 1
Affiliation
SARS-CoV-2 enters host cells by binding angiotensin-converting enzyme 2 (ACE2). Through a genome-wide association study, we show that a rare variant (MAF = 0.3%, odds ratio 0.60, P=4.5x10-13) that down-regulates ACE2 expression reduces risk of COVID-19 disease, providing human genetics support for the hypothesis that ACE2 levels influence COVID-19 risk. Further, we show that common genetic variants define a risk score that predicts severe disease among COVID-19 cases.
中文翻译：
对 756,646 名个体的全基因组分析提供了第一个遗传证据，表明 ACE2 表达影响 COVID-19 风险并产生预测严重疾病的遗传风险评分
SARS-CoV-2 通过结合血管紧张素转换酶 2 (ACE2) 进入宿主细胞。通过全基因组关联研究，我们表明下调 ACE2 表达的罕见变异（MAF = 0.3%，优势比 0.60，P=4.5x10-13）可降低 COVID-19 疾病的风险，为人类遗传学提供支持ACE2 水平影响 COVID-19 风险的假设。此外，我们表明，常见的遗传变异定义了一个风险评分，可预测 COVID-19 病例中的严重疾病。
更新日期：2021-06-11
中文翻译：
对 756,646 名个体的全基因组分析提供了第一个遗传证据，表明 ACE2 表达影响 COVID-19 风险并产生预测严重疾病的遗传风险评分
SARS-CoV-2 通过结合血管紧张素转换酶 2 (ACE2) 进入宿主细胞。通过全基因组关联研究，我们表明下调 ACE2 表达的罕见变异（MAF = 0.3%，优势比 0.60，P=4.5x10-13）可降低 COVID-19 疾病的风险，为人类遗传学提供支持ACE2 水平影响 COVID-19 风险的假设。此外，我们表明，常见的遗传变异定义了一个风险评分，可预测 COVID-19 病例中的严重疾病。
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