Association between Alzheimer’s disease and COVID-19: A bidirectional Mendelian randomization

Liu, Di; Zhang, Xiaoyu; Cao, Weijie; Zhang, Jie; Song, Manshu; Xing, Weijia; Wang, Wei; Meng, Qun; Wang, Youxin

doi:10.1101/2020.07.27.20163212

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…Future genetic analyses with larger sample sizes or clinical experiments are required to fully identify the relationship between smoking and COVID-19. The genetically predicted late-onset AD was also shown to be significantly associated with a higher risk of infection based on both UKBB and HGI report, which is not observed in another recent MR analysis 64 . This is possibly due to the larger case number (35,274 compared with 17,008) was included in late-onset AD GWAS, thus increased the power of the MR analysis.…”

Section: Discussionmentioning

confidence: 78%

Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

Ying

Zhai

Pyrkov

et al. 2020

Preprint

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Epidemiological studies have revealed that the elderly and those with co-morbidities are most susceptible to COVID-19. To understand the genetic link between aging and the risk of COVID-19, we conducted a multi-instrument Mendelian randomization analysis and found that the genetic variation that leads to a longer lifespan is significantly associated with a lower risk of COVID-19 infection. The odds ratio is 0.32 (95% CI: 0.18 to 0.57; P = 1.3 × 10-4) per additional 10 years of life, and 0.62 (95% CI: 0.51 to 0.77; P = 7.2 × 10-6) per unit higher log odds of surviving to the 90th percentile age. On the other hand, there was no association between COVID-19 susceptibility and healthspan (the lifespan free of the top seven age-related morbidities). To examine the relationship at the phenotypic level, we applied various biological aging clock models and detected an association between the biological age acceleration and future incidence and severity of COVID-19 infection for all subjects as well as for the individuals free of chronic disease. Biological age acceleration was also significantly associated with the risk of death in COVID-19 patients. Our findings suggest a causal relationship between aging and COVID-19, defined by genetic variance, the rate of aging, and the burden of chronic diseases.

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Section: Discussionmentioning

confidence: 78%

Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

Ying

Zhai

Pyrkov

et al. 2020

Preprint

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“…82 Another study that was published in a peer-reviewed journal showed accelerated ageing was associated with higher COVID-19 risk, although the publication was not indexed in PubMed. 102 However, there were methodological concerns in some studies, such as interpreting liability as the effect of disease diagnosis, 87 the lack of comprehensive assessment of IV assumptions 96 and insufficient details for replication. 100 …”

Section: Resultsmentioning

confidence: 99%

Identifying factors contributing to increased susceptibility to COVID-19 risk: a systematic review of Mendelian randomization studies

Luo

Liang

Wong

et al. 2022

International Journal of Epidemiology

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Background To summarize modifiable factors for coronavirus disease 2019 (COVID-19) suggested by Mendelian randomization studies. Methods In this systematic review, we searched PubMed, EMBASE and MEDLINE, from inception to 15 November 2021, for Mendelian randomization studies in English. We selected studies that assessed associations of genetically predicted exposures with COVID-19-related outcomes (severity, hospitalization and susceptibility). Risk of bias of the included studies was evaluated based on the consideration of the three main assumptions for instrumental variable analyses. Results We identified 700 studies through systematic search, of which 50 Mendelian randomization studies were included. Included studies have explored a wide range of socio-demographic factors, lifestyle attributes, anthropometrics and biomarkers, predisposition to diseases and druggable targets in COVID-19 risk. Mendelian randomization studies suggested that increases in smoking, obesity and inflammatory factors were associated with higher risk of COVID-19. Predisposition to ischaemic stroke, combined bipolar disorder and schizophrenia, attention-deficit and hyperactivity disorder, chronic kidney disease and idiopathic pulmonary fibrosis was potentially associated with higher COVID-19 risk. Druggable targets, such as higher protein expression of histo-blood group ABO system transferase (ABO), interleukin (IL)-6 and lower protein expression of 2′-5′ oligoadenylate synthetase 1 (OAS1) were associated with higher risk of COVID-19. There was no strong genetic evidence supporting the role of vitamin D, glycaemic traits and predisposition to cardiometabolic diseases in COVID-19 risk. Conclusion This review summarizes modifiable factors for intervention (e.g. smoking, obesity and inflammatory factors) and proteomic signatures (e.g. OAS1 and IL-6) that could help identify drugs for treating COVID-19.

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“…For instance, BMI and smoking are associated with an increased COVID-19 risk, while no evidence of causal effects was found for circulating 25-hydroxyvitamin D (25OHD) levels [18][19][20] . However, inconsistent results were also reported for some factors, such as Alzheimer's disease, blood lipids, and physical activity 18,19,[21][22][23][24][25][26] . Some of these inconsistencies are likely due to the usage of early genome-wide association studies (GWAS) of COVID-19, which have small sample sizes.…”

Section: Introductionmentioning

confidence: 99%

Prioritizing Causal Risk Factors for Severe COVID-19: An Exhaustive Mendelian Randomization Study

Sun¹,

Zhou²,

Ye³

2021

Preprint

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Identifying causal risk factors for severe coronavirus disease 2019 (COVID-19) is critical for its prevention and treatment. Many associated pre-existing conditions and biomarkers have been reported, but these observational associations suffer from confounding and reverse causation. Here, we perform a large-scale two-sample Mendelian randomization (MR) analysis to evaluate the causal roles of many traits in severe COVID-19. Our results highlight multiple body mass index (BMI)-related traits as risk-increasing: BMI (OR:1.89, 95% CI:1.51–2.37), hip circumference (OR:1.46, 1.15–1.85), and waist circumference (OR:1.82, 1.36–2.43). Our multivariable MR analysis further shows that the BMI-related effect is driven by fat mass (OR:1.63, 1.03–2.58), but not fat-free mass (OR:1.00, 0.61–1.66). Several white blood cell counts are negatively associated with severe COVID-19, including those of neutrophils (OR:0.76, 0.61–0.94), granulocytes (OR:0.75, 0.601–0.93), and myeloid white blood cells (OR:0.77, 0.62–0.96). Furthermore, some circulating proteins are associated with an increased risk of (e.g., zinc-alpha-2-glycoprotein) or protection from severe COVID-19 (e.g., interleukin-3/6 receptor subunit alpha). Our study shows that fat mass and white blood cells underlie the etiology of severe COVID-19. It also identifies risk and protective factors that could serve as drug targets and guide the effective protection of high-risk individuals.

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Association between Alzheimer’s disease and COVID-19: A bidirectional Mendelian randomization

Cited by 4 publications

References 33 publications

Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

Identifying factors contributing to increased susceptibility to COVID-19 risk: a systematic review of Mendelian randomization studies

Prioritizing Causal Risk Factors for Severe COVID-19: An Exhaustive Mendelian Randomization Study

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Association between Alzheimer’s disease and COVID-19: A bidirectional Mendelian randomization

Cited by 4 publications

References 33 publications

Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

Identifying factors contributing to increased susceptibility to COVID-19 risk: a systematic review of Mendelian randomization studies

Prioritizing Causal Risk Factors for Severe&nbsp;COVID-19: An Exhaustive Mendelian Randomization Study

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Product

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Prioritizing Causal Risk Factors for Severe COVID-19: An Exhaustive Mendelian Randomization Study