dc.contributor.author | Tragante, V | |
dc.contributor.author | Hemerich, D | |
dc.contributor.author | Alshabeeb, M | |
dc.contributor.author | Braenne, I | |
dc.contributor.author | Lempiaeinen, H | |
dc.contributor.author | Patel, RS | |
dc.contributor.author | den Ruijter, HM | |
dc.contributor.author | Barnes, MR | |
dc.contributor.author | Moore, JH | |
dc.contributor.author | Schunkert, H | |
dc.contributor.author | Erdmann, J | |
dc.contributor.author | Asselbergs, FW | |
dc.date.accessioned | 2019-08-13T07:41:24Z | |
dc.date.available | 2018-08-12 | |
dc.date.available | 2019-08-13T07:41:24Z | |
dc.date.issued | 2018-08-13 | |
dc.identifier.issn | 2574-8300 | |
dc.identifier.other | UNSP e001977 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/59036 | |
dc.description.abstract | Background:
Genome-wide association studies have identified multiple loci associated with coronary artery disease and myocardial infarction, but only a few of these loci are current targets for on-market medications. To identify drugs suitable for repurposing and their targets, we created 2 unique pipelines integrating public data on 49 coronary artery disease/myocardial infarction–genome-wide association studies loci, drug-gene interactions, side effects, and chemical interactions.
Methods:
We first used publicly available genome-wide association studies results on all phenotypes to predict relevant side effects, identified drug-gene interactions, and prioritized candidates for repurposing among existing drugs. Second, we prioritized gene product targets by calculating a druggability score to estimate how accessible pockets of coronary artery disease/myocardial infarction–associated gene products are, then used again the genome-wide association studies results to predict side effects, excluded loci with widespread cross-tissue expression to avoid housekeeping and genes involved in vital processes and accordingly ranked the remaining gene products.
Results:
These pipelines ultimately led to 3 suggestions for drug repurposing: pentolinium, adenosine triphosphate, and riociguat (to target CHRNB4, ACSS2, and GUCY1A3, respectively); and 3 proteins for drug development: LMOD1 (leiomodin 1), HIP1 (huntingtin-interacting protein 1), and PPP2R3A (protein phosphatase 2, regulatory subunit b-double prime, α). Most current therapies for coronary artery disease/myocardial infarction treatment were also rediscovered.
Conclusions:
Integration of genomic and pharmacological data may prove beneficial for drug repurposing and development, as evidence from our pipelines suggests. | en_US |
dc.publisher | American Heart Association, Inc. | en_US |
dc.relation.ispartof | CIRCULATION-GENOMIC AND PRECISION MEDICINE | |
dc.subject | coronary artery disease | en_US |
dc.subject | drug interactions | en_US |
dc.subject | genome-wide | en_US |
dc.subject | association study | en_US |
dc.subject | myocardial infarction | en_US |
dc.subject | pharmacogenetics | en_US |
dc.title | Druggability of Coronary Artery Disease Risk Loci | en_US |
dc.type | Article | en_US |
dc.rights.holder | © 2018 American Heart Association, Inc. | |
dc.identifier.doi | 10.1161/CIRCGEN.117.001977 | |
pubs.author-url | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000444529200002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a | en_US |
pubs.issue | 8 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.publisher-url | https://doi.org/10.1161/CIRCGEN.117.001977 | |
pubs.volume | 11 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |