tetano
Editor, Senior Moderator
CNS Neurosci Ther
. 2024 Jul;30(7):e14873.
doi: 10.1111/cns.14873. Shared genetics and causal association between plasma levels of SARS-CoV-2 entry receptor ACE2 and Alzheimer's disease
Yan Zhang[SUP] 1 [/SUP], Fang Xu[SUP] 2 [/SUP], Tao Wang[SUP] 3 4 [/SUP], Zhifa Han[SUP] 5 [/SUP], Hong Shang[SUP] 6 [/SUP], Kevin Han[SUP] 7 [/SUP], Ping Zhu[SUP] 8 [/SUP], Shan Gao[SUP] 8 [/SUP], Xiaojie Wang[SUP] 9 [/SUP], Yanli Xue[SUP] 10 [/SUP], Chen Huang[SUP] 11 [/SUP], Yan Chen[SUP] 12 13 [/SUP], Guiyou Liu[SUP] 8 12 13 14 15 16 [/SUP]
Affiliations
Background: Alzheimer's disease (AD) is the highest risk of COVID-19 infection, hospitalization, and mortality. However, it remains largely unclear about the link between AD and COVID-19 outcomes. ACE2 is an entry receptor for SARS-CoV-2. Circulating ACE2 is a novel biomarker of death and associated with COVID-19 outcomes.
Methods: Here, we explored the shared genetics and causal association between AD and plasma ACE2 levels using large-scale genome-wide association study, gene expression, expression quantitative trait loci, and high-throughput plasma proteomic profiling datasets.
Results: We found a significant causal effect of genetically increased circulating ACE2 on increased risk of AD. Cross-trait association analysis identified 19 shared genetic variants, and three variants rs3104412, rs2395166, and rs3135344 at chromosome 6p21.32 were associated with COVID-19 infection, hospitalization, and severity. We mapped 19 variants to 117 genes, which were significantly upregulated in lung, spleen, and small intestine, downregulated in brain tissues, and involved in immune system, immune disease, and infectious disease pathways. The plasma proteins corresponding to LST1, AGER, TNXB, and APOC1 were predominantly associated with COVID-19 infection, ventilation, and death.
Conclusion: Together, our findings suggest the shared genetics and causal association between AD and plasma ACE2 levels, which may partially explain the link between AD and COVID-19.
Keywords: ACE2; Alzheimer's disease; COVID‐19; SARS‐CoV‐2; expression quantitative trait loci; gene expression; genome‐wide association study.
. 2024 Jul;30(7):e14873.
doi: 10.1111/cns.14873. Shared genetics and causal association between plasma levels of SARS-CoV-2 entry receptor ACE2 and Alzheimer's disease
Yan Zhang[SUP] 1 [/SUP], Fang Xu[SUP] 2 [/SUP], Tao Wang[SUP] 3 4 [/SUP], Zhifa Han[SUP] 5 [/SUP], Hong Shang[SUP] 6 [/SUP], Kevin Han[SUP] 7 [/SUP], Ping Zhu[SUP] 8 [/SUP], Shan Gao[SUP] 8 [/SUP], Xiaojie Wang[SUP] 9 [/SUP], Yanli Xue[SUP] 10 [/SUP], Chen Huang[SUP] 11 [/SUP], Yan Chen[SUP] 12 13 [/SUP], Guiyou Liu[SUP] 8 12 13 14 15 16 [/SUP]
Affiliations
- PMID: 39056224
- PMCID: PMC11273102
- DOI: 10.1111/cns.14873
Background: Alzheimer's disease (AD) is the highest risk of COVID-19 infection, hospitalization, and mortality. However, it remains largely unclear about the link between AD and COVID-19 outcomes. ACE2 is an entry receptor for SARS-CoV-2. Circulating ACE2 is a novel biomarker of death and associated with COVID-19 outcomes.
Methods: Here, we explored the shared genetics and causal association between AD and plasma ACE2 levels using large-scale genome-wide association study, gene expression, expression quantitative trait loci, and high-throughput plasma proteomic profiling datasets.
Results: We found a significant causal effect of genetically increased circulating ACE2 on increased risk of AD. Cross-trait association analysis identified 19 shared genetic variants, and three variants rs3104412, rs2395166, and rs3135344 at chromosome 6p21.32 were associated with COVID-19 infection, hospitalization, and severity. We mapped 19 variants to 117 genes, which were significantly upregulated in lung, spleen, and small intestine, downregulated in brain tissues, and involved in immune system, immune disease, and infectious disease pathways. The plasma proteins corresponding to LST1, AGER, TNXB, and APOC1 were predominantly associated with COVID-19 infection, ventilation, and death.
Conclusion: Together, our findings suggest the shared genetics and causal association between AD and plasma ACE2 levels, which may partially explain the link between AD and COVID-19.
Keywords: ACE2; Alzheimer's disease; COVID‐19; SARS‐CoV‐2; expression quantitative trait loci; gene expression; genome‐wide association study.