Gene-Environment Interaction Analysis Incorporating Sex, Cardiometabolic Diseases, and Multiple Deprivation Index Reveals Novel Genetic Associations With COVID-19 Severity.
Gene-Environment Interaction Analysis Incorporating Sex, Cardiometabolic Diseases, and Multiple Deprivation Index Reveals Novel Genetic Associations With COVID-19 Severity.
复制标题
DOI：
10.3389/fgene.2021.782172
复制
发表时间：
2021
影响因子：
3.7
通讯作者：
Manning AK
中科院分区：
文献类型：
--
作者：
Westerman KE;Lin J;Sevilla-Gonzalez MDR;Tadess B;Marchek C;Manning AK
越来越多的证据表明，特定的遗传变异会影响感染COVID-19后结果的严重程度。然而，目前尚不清楚这些遗传因素的影响是否独立于由于更确定的非遗传人口统计学和代谢风险因素，如男性，心脏代谢健康状况差，社会经济地位低的风险。我们试图通过英国生物库的全基因组相互作用研究，确定影响COVID-19严重程度的遗传变异和非遗传风险因素之间的相互作用。在378，051名欧洲血统的无关个体中，2，402人被归类为经历了严重的COVID-19，定义为因COVID-19住院或死亡。暴露包括性别、心脏代谢风险因素[肥胖和2型糖尿病（T2 D），联合检测]和多重剥夺指数。使用逻辑回归模型测试乘法交互作用，进行交互作用测试和遗传主效应和交互作用的联合测试。五个独立的变异在联合测试中达到全基因组显著性，其中一个在相互作用测试中也达到显著性。其中之一，胎盘生长因子（PGF）基因中的rs 2268616，在男性和T2 D患者中表现出更强的作用。在COVID-19宿主遗传学倡议的查找中，这五种变体都没有对类似定义的表型产生影响。这些结果揭示了导致COVID-19严重程度的潜在额外遗传位点，并证明了在遗传发现的相互作用测试方法中包括非遗传风险因素的价值。
Increasing evidence indicates that specific genetic variants influence the severity of outcomes after infection with COVID-19. However, it is not clear whether the effect of these genetic factors is independent of the risk due to more established non-genetic demographic and metabolic risk factors such as male sex, poor cardiometabolic health, and low socioeconomic status. We sought to identify interactions between genetic variants and non-genetic risk factors influencing COVID-19 severity via a genome-wide interaction study in the UK Biobank. Of 378,051 unrelated individuals of European ancestry, 2,402 were classified as having experienced severe COVID-19, defined as hospitalization or death due to COVID-19. Exposures included sex, cardiometabolic risk factors [obesity and type 2 diabetes (T2D), tested jointly], and multiple deprivation index. Multiplicative interaction was tested using a logistic regression model, conducting both an interaction test and a joint test of genetic main and interaction effects. Five independent variants reached genome-wide significance in the joint test, one of which also reached significance in the interaction test. One of these, rs2268616 in the placental growth factor (PGF) gene, showed stronger effects in males and in individuals with T2D. None of the five variants showed effects on a similarly-defined phenotype in a lookup in the COVID-19 Host Genetics Initiative. These results reveal potential additional genetic loci contributing to COVID-19 severity and demonstrate the value of including non-genetic risk factors in an interaction testing approach for genetic discovery.
登录
查看更多内容
影响因子：
11.8
作者：
Tai, Don Bambino Geno;Shah, Aditya;Wieland, Mark L.
通讯作者：
Wieland, Mark L.
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
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：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
3.7
作者：
Lau ES;McNeill JN;Paniagua SM;Liu EE;Wang JK;Bassett IV;Selvaggi CA;Lubitz SA;Foulkes AS;Ho JE
通讯作者：
Ho JE