Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study
BackgroundCross-sectional observational studies have reported obesity and cardiometabolic co-morbidities as important predictors of coronavirus disease 2019 (COVID-19) hospitalization. The causal impact of these risk factors is unknown at present.MethodsWe conducted multivariable logistic regression...
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doaj-77c12008f6104b81b678c912f90e41112020-11-25T04:09:51ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-11-011110.3389/fgene.2020.586308586308Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization StudyNay Aung0Nay Aung1Mohammed Y. Khanji2Mohammed Y. Khanji3Patricia B. Munroe4Patricia B. Munroe5Steffen E. Petersen6Steffen E. Petersen7Barts Heart Centre, Barts Health NHS Trust, London, United KingdomWilliam Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, United KingdomBarts Heart Centre, Barts Health NHS Trust, London, United KingdomWilliam Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, United KingdomBarts Heart Centre, Barts Health NHS Trust, London, United KingdomWilliam Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, United KingdomBarts Heart Centre, Barts Health NHS Trust, London, United KingdomWilliam Harvey Research Institute, NIHR Barts Biomedical Research Centre, Queen Mary University of London, London, United KingdomBackgroundCross-sectional observational studies have reported obesity and cardiometabolic co-morbidities as important predictors of coronavirus disease 2019 (COVID-19) hospitalization. The causal impact of these risk factors is unknown at present.MethodsWe conducted multivariable logistic regression to evaluate the observational associations between obesity traits (body mass index [BMI], waist circumference [WC]), quantitative cardiometabolic parameters (systolic blood pressure [SBP], serum glucose, serum glycated hemoglobin [HbA1c], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and SARS-CoV-2 positivity in the UK Biobank cohort. One-sample MR was performed by using the genetic risk scores of obesity and cardiometabolic traits constructed from independent datasets and the genotype and phenotype data from the UK Biobank. Two-sample MR was performed using the summary statistics from COVID-19 host genetics initiative. Cox proportional hazard models were fitted to assess the risk conferred by different genetic quintiles of causative exposure traits.ResultsThe study comprised 1,211 European participants who were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 387,079 participants who were either untested or tested negative between 16 March 2020 to 31 May 2020. Observationally, higher BMI, WC, HbA1c and lower HDL-cholesterol were associated with higher odds of COVID-19 infection. One-sample MR analyses found causal associations between higher genetically determined BMI and LDL cholesterol and increased risk of COVID-19 (odds ratio [OR]: 1.15, confidence interval [CI]: 1.05–1.26 and OR: 1.58, CI: 1.21–2.06, per 1 standard deviation increment in BMI and LDL cholesterol respectively). Two-sample MR produced concordant results. Cox models indicated that individuals in the higher genetic risk score quintiles of BMI and LDL were more predisposed to COVID-19 (hazard ratio [HR]: 1.24, CI: 1.03–1.49 and HR: 1.37, CI: 1.14–1.65, for the top vs the bottom quintile for BMI and LDL cholesterol, respectively).ConclusionWe identified causal associations between BMI, LDL cholesterol and susceptibility to COVID-19. In particular, individuals in higher genetic risk categories were predisposed to SARS-CoV-2 infection. These findings support the integration of BMI into the risk assessment of COVID-19 and allude to a potential role of lipid modification in the prevention and treatment.https://www.frontiersin.org/articles/10.3389/fgene.2020.586308/fullobesitylipid profilemendelian randomizationCOVID-19SARS-CoV-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nay Aung Nay Aung Mohammed Y. Khanji Mohammed Y. Khanji Patricia B. Munroe Patricia B. Munroe Steffen E. Petersen Steffen E. Petersen |
spellingShingle |
Nay Aung Nay Aung Mohammed Y. Khanji Mohammed Y. Khanji Patricia B. Munroe Patricia B. Munroe Steffen E. Petersen Steffen E. Petersen Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study Frontiers in Genetics obesity lipid profile mendelian randomization COVID-19 SARS-CoV-2 |
author_facet |
Nay Aung Nay Aung Mohammed Y. Khanji Mohammed Y. Khanji Patricia B. Munroe Patricia B. Munroe Steffen E. Petersen Steffen E. Petersen |
author_sort |
Nay Aung |
title |
Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study |
title_short |
Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study |
title_full |
Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study |
title_fullStr |
Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study |
title_full_unstemmed |
Causal Inference for Genetic Obesity, Cardiometabolic Profile and COVID-19 Susceptibility: A Mendelian Randomization Study |
title_sort |
causal inference for genetic obesity, cardiometabolic profile and covid-19 susceptibility: a mendelian randomization study |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Genetics |
issn |
1664-8021 |
publishDate |
2020-11-01 |
description |
BackgroundCross-sectional observational studies have reported obesity and cardiometabolic co-morbidities as important predictors of coronavirus disease 2019 (COVID-19) hospitalization. The causal impact of these risk factors is unknown at present.MethodsWe conducted multivariable logistic regression to evaluate the observational associations between obesity traits (body mass index [BMI], waist circumference [WC]), quantitative cardiometabolic parameters (systolic blood pressure [SBP], serum glucose, serum glycated hemoglobin [HbA1c], low-density lipoprotein [LDL] cholesterol, high-density lipoprotein [HDL] cholesterol and triglycerides [TG]) and SARS-CoV-2 positivity in the UK Biobank cohort. One-sample MR was performed by using the genetic risk scores of obesity and cardiometabolic traits constructed from independent datasets and the genotype and phenotype data from the UK Biobank. Two-sample MR was performed using the summary statistics from COVID-19 host genetics initiative. Cox proportional hazard models were fitted to assess the risk conferred by different genetic quintiles of causative exposure traits.ResultsThe study comprised 1,211 European participants who were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 387,079 participants who were either untested or tested negative between 16 March 2020 to 31 May 2020. Observationally, higher BMI, WC, HbA1c and lower HDL-cholesterol were associated with higher odds of COVID-19 infection. One-sample MR analyses found causal associations between higher genetically determined BMI and LDL cholesterol and increased risk of COVID-19 (odds ratio [OR]: 1.15, confidence interval [CI]: 1.05–1.26 and OR: 1.58, CI: 1.21–2.06, per 1 standard deviation increment in BMI and LDL cholesterol respectively). Two-sample MR produced concordant results. Cox models indicated that individuals in the higher genetic risk score quintiles of BMI and LDL were more predisposed to COVID-19 (hazard ratio [HR]: 1.24, CI: 1.03–1.49 and HR: 1.37, CI: 1.14–1.65, for the top vs the bottom quintile for BMI and LDL cholesterol, respectively).ConclusionWe identified causal associations between BMI, LDL cholesterol and susceptibility to COVID-19. In particular, individuals in higher genetic risk categories were predisposed to SARS-CoV-2 infection. These findings support the integration of BMI into the risk assessment of COVID-19 and allude to a potential role of lipid modification in the prevention and treatment. |
topic |
obesity lipid profile mendelian randomization COVID-19 SARS-CoV-2 |
url |
https://www.frontiersin.org/articles/10.3389/fgene.2020.586308/full |
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