PMID- 33140059
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240216
DP  - 2020 Oct 28
TI  - ACE2 Netlas: In-silico functional characterization and drug-gene interactions of 
      ACE2 gene network to understand its potential involvement in COVID-19 
      susceptibility.
LID - 2020.10.27.20220665 [pii]
LID - 10.1101/2020.10.27.20220665 [doi]
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 a multi-level characterization 
      of genes that interact with ACE2 (ACE2-gene network) for their over-represented 
      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 characterized functional consequences (among others) using miRNA binding-site 
      targets. MiRNAs affected by ACE2-network variants revealed statistical 
      over-representation of inflammation, aging, diabetes, and heart conditions. With 
      respect to variants mapped to the ACE2-network, we observed COVID-19 related 
      associations in RORA, SLC12A6 and SLC6A19 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/.
FAU - Pathak, Gita A
AU  - Pathak GA
AD  - Yale School of Medicine, Department of Psychiatry, Division of Human Genetics, 
      New Haven, CT Veteran Affairs Connecticut Healthcare System, West Haven, CT.
FAU - Wendt, Frank R
AU  - Wendt FR
AD  - Yale School of Medicine, Department of Psychiatry, Division of Human Genetics, 
      New Haven, CT Veteran Affairs Connecticut Healthcare System, West Haven, CT.
FAU - Goswami, Aranyak
AU  - Goswami A
AD  - Yale School of Medicine, Department of Psychiatry, Division of Human Genetics, 
      New Haven, CT Veteran Affairs Connecticut Healthcare System, West Haven, CT.
FAU - Angelis, Flavio De
AU  - Angelis F
AD  - Yale School of Medicine, Department of Psychiatry, Division of Human Genetics, 
      New Haven, CT Veteran Affairs Connecticut Healthcare System, West Haven, CT.
CN  - COVID-19 Human Genetics Initiative
FAU - Polimanti, Renato
AU  - Polimanti R
AD  - Yale School of Medicine, Department of Psychiatry, Division of Human Genetics, 
      New Haven, CT Veteran Affairs Connecticut Healthcare System, West Haven, CT.
LA  - eng
GR  - F32 MH122058/MH/NIMH NIH HHS/United States
GR  - R01 DA012690/DA/NIDA NIH HHS/United States
GR  - R21 DA047527/DA/NIDA NIH HHS/United States
GR  - R21 DC018098/DC/NIDCD NIH HHS/United States
PT  - Preprint
DEP - 20201028
PL  - United States
TA  - medRxiv
JT  - medRxiv : the preprint server for health sciences
JID - 101767986
UIN - Front Genet. 2021 Aug 27;12:698033. PMID: 34512723
PMC - PMC7605570
COIS- Competing Interests The authors have no competing interests.
EDAT- 2020/11/04 06:00
MHDA- 2020/11/04 06:01
PMCR- 2020/11/02
CRDT- 2020/11/03 05:47
PHST- 2020/11/03 05:47 [entrez]
PHST- 2020/11/04 06:00 [pubmed]
PHST- 2020/11/04 06:01 [medline]
PHST- 2020/11/02 00:00 [pmc-release]
AID - 2020.10.27.20220665 [pii]
AID - 10.1101/2020.10.27.20220665 [doi]
PST - epublish
SO  - medRxiv [Preprint]. 2020 Oct 28:2020.10.27.20220665. doi: 
      10.1101/2020.10.27.20220665.