PMID- 34512723
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231102
IS  - 1664-8021 (Print)
IS  - 1664-8021 (Electronic)
IS  - 1664-8021 (Linking)
VI  - 12
DP  - 2021
TI  - ACE2 Netlas: In silico Functional Characterization and Drug-Gene Interactions of 
      ACE2 Gene Network to Understand Its Potential Involvement in COVID-19 
      Susceptibility.
PG  - 698033
LID - 10.3389/fgene.2021.698033 [doi]
LID - 698033
AB  - Angiotensin-converting enzyme-2 (ACE2) receptor has been identified as the key 
      adhesion molecule for the transmission of the SARS-CoV-2. However, there is no 
      evidence that human genetic variation in ACE2 is singularly responsible for 
      COVID-19 susceptibility. Therefore, we performed an integrative multi-level 
      characterization of genes that interact with ACE2 (ACE2-gene network) for their 
      statistically enriched biological properties in the context of COVID-19. The 
      phenome-wide association of 51 genes including ACE2 with 4,756 traits categorized 
      into 26 phenotype categories, showed enrichment of immunological, respiratory, 
      environmental, skeletal, dermatological, and metabolic domains (p < 4e-4). 
      Transcriptomic regulation of ACE2-gene network was enriched for 
      tissue-specificity in kidney, small intestine, and colon (p < 4.7e-4). Leveraging 
      the drug-gene interaction database we identified 47 drugs, including 
      dexamethasone and spironolactone, among others. Considering genetic variants 
      within +/- 10 kb of ACE2-network genes we identified miRNAs whose binding sites may 
      be altered as a consequence of genetic variation. The identified miRNAs revealed 
      statistical over-representation of inflammation, aging, diabetes, and heart 
      conditions. The genetic variant associations in RORA, SLC12A6, and SLC6A19 genes 
      were observed in genome-wide association study (GWAS) of COVID-19 susceptibility. 
      We also report the GWAS-identified variant in 3p21.31 locus, serves as trans-QTL 
      for RORA and RORC genes. Overall, functional characterization of ACE2-gene 
      network highlights several potential mechanisms in COVID-19 susceptibility. The 
      data can also be accessed at https://gpwhiz.github.io/ACE2Netlas/.
CI  - Copyright (c) 2021 Pathak, Wendt, Goswami, Koller, De Angelis, COVID-19 Host 
      Genetics Initiative and Polimanti.
FAU - Pathak, Gita A
AU  - Pathak GA
AD  - Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, 
      New Haven, CT, United States.
AD  - Veteran Affairs Connecticut Healthcare System, West Haven, CT, United States.
FAU - Wendt, Frank R
AU  - Wendt FR
AD  - Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, 
      New Haven, CT, United States.
AD  - Veteran Affairs Connecticut Healthcare System, West Haven, CT, United States.
FAU - Goswami, Aranyak
AU  - Goswami A
AD  - Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, 
      New Haven, CT, United States.
AD  - Veteran Affairs Connecticut Healthcare System, West Haven, CT, United States.
FAU - Koller, Dora
AU  - Koller D
AD  - Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, 
      New Haven, CT, United States.
AD  - Veteran Affairs Connecticut Healthcare System, West Haven, CT, United States.
FAU - De Angelis, Flavio
AU  - De Angelis F
AD  - Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, 
      New Haven, CT, United States.
AD  - Veteran Affairs Connecticut Healthcare System, West Haven, CT, United States.
CN  - COVID-19 Host Genetics Initiative
FAU - Polimanti, Renato
AU  - Polimanti R
AD  - Division of Human Genetics, Department of Psychiatry, Yale School of Medicine, 
      New Haven, CT, United States.
AD  - Veteran Affairs Connecticut Healthcare System, West Haven, CT, United States.
LA  - eng
GR  - F32 MH122058/MH/NIMH NIH HHS/United States
GR  - R21 DA047527/DA/NIDA NIH HHS/United States
GR  - R21 DC018098/DC/NIDCD NIH HHS/United States
PT  - Journal Article
DEP - 20210827
PL  - Switzerland
TA  - Front Genet
JT  - Frontiers in genetics
JID - 101560621
UOF - medRxiv. 2020 Oct 28;:. PMID: 33140059
PMC - PMC8429844
OTO - NOTNLM
OT  - ACE2
OT  - COVID-19
OT  - immune response
OT  - miRNA
OT  - network
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/09/14 06:00
MHDA- 2021/09/14 06:01
PMCR- 2021/08/27
CRDT- 2021/09/13 06:44
PHST- 2021/05/07 00:00 [received]
PHST- 2021/07/29 00:00 [accepted]
PHST- 2021/09/13 06:44 [entrez]
PHST- 2021/09/14 06:00 [pubmed]
PHST- 2021/09/14 06:01 [medline]
PHST- 2021/08/27 00:00 [pmc-release]
AID - 10.3389/fgene.2021.698033 [doi]
PST - epublish
SO  - Front Genet. 2021 Aug 27;12:698033. doi: 10.3389/fgene.2021.698033. eCollection 
      2021.