Nucleic Acids Research, 2023, 1–8

https://doi.org/10.1093/nar/gkad832
Database issue

PharmGWAS: a GWAS-based knowledgebase for drug

repurposing
1 ,2
Hongen Kang , Siyu Pan1 ,2 , Shiqi Lin1 ,2 , Yin-Ying Wang1 , Na Yuan 1
and Peilin Jia 1 ,2 ,3 ,
*

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1
CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and China National
Center for Bioinformation, Beijing 100101, China
2
University of Chinese Academy of Sciences, Beijing 100049, China
3
National Genomics Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation,
Beijing 100101, China
*
To whom correspondence should be addressed. Tel: +86 10 84097798; Email: pjia@big.ac.cn

Abstract
Leveraging genetics insights to promote drug repurposing has become a promising and active strategy in pharmacology. Indeed, among the
50 drugs approved by FDA in 2021, two-thirds have genetically supported evidence. In this regard, the increasing amount of widely available
genome-wide association studies (GWAS) datasets have provided substantial opportunities for drug repurposing based on genetics discoveries.
Here, we developed PharmGWAS, a comprehensive knowledgebase designed to identify candidate drugs through the integration of GWAS data.
PharmGWAS focuses on novel connections between diseases and small-molecule compounds derived using a reverse relationship between the
genetically-regulated expression signature and the drug-induced signature. Specifically, we collected and processed 1929 GWAS datasets across
a diverse spectrum of diseases and 724 485 perturbation signatures pertaining to a substantial 33609 molecular compounds. To obtain reliable and
robust predictions for the reverse connections, we implemented six distinct connectivity methods. In the current version, PharmGWAS deposits
a total of 740 227 genetically-informed disease-drug pairs derived from drug-perturbation signatures, presenting a valuable and comprehensive
catalog. Further equipped with its user-friendly web design, PharmGWAS is expected to greatly aid the discovery of novel drugs, the exploration
of drug combination therapies and the identification of drug resistance or side effects. PharmGWAS is available at https://ngdc.cncb.ac.cn/
pharmgwas.

Graphical abstract
Genetically regulated Drug induced
expression profiles expression profiles

GWA
W S summary
statistics

S-PrediXcan

Connectivity
methods

Drug repurposing candidates

Introduction existing medications or drugs, offering accelerated timelines,

The development of novel drugs is a daunting and time- and
cost-consuming process, which severely impedes the transla-
tion of scientific breakthroughs into clinical applications (1,2).
To address this challenge, drug repurposing, also known as
drug repositioning, has emerged as a promising strategy. Drug
repurposing seeks to identify novel clinical applications for
reduced risks and lower expenses compared to the traditional
de novo drug discovery pipeline.
Diverse computational approaches have been developed to
aid the identification of repurposing candidates, such as sig-
nature matching, molecular docking and retrospective clini-
cal analysis and so on (3). Among these, the signature match-

Received: August 14, 2023. Revised: September 12, 2023. Editorial Decision: September 19, 2023. Accepted: September 21, 2023
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License
(http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the
original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
2 Nucleic Acids Research, 2023

ing approach, also called the connectivity approach, has been
proven particularly effective in discovering new drug repur-
posing candidates across a wide spectrum of therapeutic do-
mains, even at the level of single-cell resolution (4–10). It usu-
ally involves the comparison of the signature of a drug, often
derived through differential gene expression analysis before
and after drug treatment, with that of another disease pheno-
type. The degree of inverse correlation between the two sig-
natures can provide insights into whether the drug may re-
vert the disease phenotype itself. Specifically, representative
signature-based methods, or connectivity methods, included
diseases and candidate drugs. PharmGWAS thus provides a
valuable reference resource by leveraging genetic evidence to
aid the discovery of novel drugs, the exploration of drug com-
bination therapies and the identification of drug resistance or
side effects.
Materials and methods
Data collection
GWAS summary statistics. We downloaded GWAS sum-

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mary statistics mainly from three sources: GWAS Cat-
the Connectivity Score, which was based on Kolmogorov-
alog (32), UK BioBank (UKBB) (33) and large con-
Smirnov (KS) statistics and was first implemented by the Con-
sortiums dedicated to diverse diseases, including Coro-
nectivity Map (CMap) project (11). Later, other methods were
nary ARtery DIsease Genome wide Replication and Meta-
reported not only measuring the strength of the inverse con-
analysis (CARDIoGRAM) plus The Coronary Artery Disease
nections but also assessing the statistical significance of the
(C4D) Genetics Consortium (34), Cerebrovascular Disease
connections (12,13), such as the Connection Strength Score
Knowledge Portal/International Stroke Genetics Consortium
(CSS) and eXtreme sum (XSum) score.
(CDKP/ISGC) (35), Common Metabolic Diseases Knowledge
Recently, advances in genome-wide association studies
Portal (CMDKP) (36), Cardiovascular Disease Knowledge
(GWAS) have revealed important biological insights into com-
Portal (CVDKP) (37,38), Reproductive Genetics Consortium
plex diseases. These genetics discoveries can assist in identi-
(RGC) (39), Psychiatric Genomic Consortium (PGC) (40) and
fying compounds suitable for tailored treatments to the re-
Sleep Disorder Knowledge Portal (SDKP) (41). According to
spective diseases (14–16). Indeed, among the 50 drugs ap-
the Experimental Factor Ontology (EFO) provided by GWAS
proved by FDA in 2021, two-thirds have genetically supported
Catalog, we filtered out the GWAS data where the trait de-
evidence (17). Traditionally, GWAS signals may provide op-
scription did not map to the disease terms in the EFO. Also,
portunities for selecting candidate drug targets by identify-
we only retained disease-related GWAS data for UKBB ac-
ing the causal variants and genes with large effect sizes (18–
cording to the international classification of diseases (ICD-
20). For example, IL23R was identified by GWAS as a re-
10), cancer code and non-cancer illness code. Considering that
purposing candidate for Crohn’s disease (21), and the corre-
the TWAS prediction models were built based on reference
sponding drug, ustekinumab, had been shown to have a sig-
data of European ancestry (42), we only kept the GWAS data
nificant therapeutic effect on IL23R (22). However, the ma-
from European ancestry in our current version of PharmG-
jority of significant variants are located in the non-coding
WAS. Redundant datasets were removed. We also collected
regions of the genome, making it quite challenging to iden-
metadata such as sample size, ancestry and release year of the
tify the causal genes. Furthermore, the majority of common
datasets from GWAS Catalog or manually reviewed the orig-
variants identified in GWAS had small to modest individ-
inal publications. The summary of GWAS datasets is shown
ual effects on traits, which may not be substantial enough
in Table 1.
for therapeutic intervention. On the contrary, the combined
Drug perturbation signatures. The drug-induced gene ex-
polygenic effect of many such variants could be considerably
pression profiles were retrieved from two sources: the Ex-
large and constitute a significant portion of the overall trait
panded CMap LINCS Resource 2020 (hereafter referred to
heritability (23–26). To leverage the discovery power of the
as CMap2.0) and the SigCom LINCS resource (30,31). For
vast majority of common variants, GWAS summary statis-
CMap2.0, we downloaded the level 5 data of small molecule
tics can be used to impute the genetically regulated expres-
compounds along with the metadata including information of
sion (GReX) profile and then compare with the drug-induced
compounds, dosage, time, genes and cell lines. SigCom LINCS
gene expression profiles, such as those generated by the Con-
is a webserver that provides service to process and analyze
nectivity Map project (11). Such extended signature matching
over a million gene expression signatures. We downloaded
strategies had been successfully applied in psychiatric disor-
the level 5 data from the SigCom LINCS resource (file name:
ders (27,28), blood traits (29) among others. However, there
Automatic Human GEO RNA-seq Signatures; access date:
is still a lack of a systematic and comprehensive knowledge-
29 May 2023), which included 4269 signatures that could also
base for genetically-informed drug repurposing for a wide
be used for connectivity analyses.
range of complex diseases.
To address this issue, we developed PharmGWAS, a knowl-
edgebase for GWAS-informed drug repurposing across a Data analysis workflow
diverse spectrum of diseases. We constructed a standard We constructed a standard pipeline to infer genetically-
computational inference workflow to first implement the informed drugs. First, because gene expression data could be
transcriptome-wide association study (TWAS) strategy and quite tissue-specific, we defined disease-associated genes us-
impute the GReX signatures in disease-relevant tissues for ing the GWAS data and conducted tissue-specific enrichment
each GWAS dataset. We also curated a comprehensive list of analysis (TSEA) to identify disease-relevant tissues for TWAS
drug-induced gene expression profiles from the CMap project analyses. Second, we applied TWAS in the predicted tissues
and the Gene Expression Omnibus (GEO) database (30,31). and obtained the imputed GReX. Third, we conducted con-
We then implemented six computational methods to search nectivity analyses to infer drug candidates by integrating the
for the drug-induced signatures that had a negative correla- GWAS-informed signature (GReX) and drug-induced signa-
tion with the GReX signature. These methods have been well- tures. Finally, we defined candidate disease-drug pairs by com-
reported and evaluated in literature to successfully connect bining the results of the six connectivity methods.
Nucleic Acids Research, 2023 3

Table 1. Summary of GWAS datasets

Source Datasets URL

UK Biobank 1551 http://www.nealelab.is/uk-biobank

GWAS Catalog 340 https://www.ebi.ac.uk/gwas/home
CARDIoGRAMplusC4D 2 http://www.cardiogramplusc4d.org/data-downloads/
CDKP/ISGC 4 https://cd.hugeamp.org/downloads.html
CMDKP 13 https://hugeamp.org/downloads.html
CVDKP 3 https://cvd.hugeamp.org/downloads.html
RGC 1 http://www.reprogen.org/data_download.html
PGC 13 https://www.med.unc.edu/pgc/results- and- downloads

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SDKP 2 https://sleep.hugeamp.org/downloads.html
CARDIoGRAMplusC4D: Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D)
Genetics, CDKP/ISGC: Cerebrovascular Disease Knowledge Portal/International Stroke Genetics Consortium, CMDKP: Common Metabolic Diseases Knowl-
edge Portal, CVDKP: Cardiovascular Disease Knowledge Portal, RGC: Reproductive Genetics Consortium, PGC: Psychiatric Genomic Consortium, SDKP:
Sleep Disorder Knowledge Portal.

Tissue-specific enrichment analysis 

NS

We used Multi-marker Analysis of GenoMic Annotation cssmax (NR, NS ) = (NR − i + 1 )

(MAGMA v1.10) (43) to calculate gene-based p-values us- i=1

ing GWAS summary statistics. We defined disease-associated

genes as those with MAGMA P < 0.05 and conducted TSEA
by using the deTS algorithm to infer disease-relevant tissues
(44). For each GWAS dataset, deTS identified the top three tis-
sues that were most relevant to the disease and had P < 0.05.
We used these tissues for the following analysis.
Transcriptome-wide association study
To impute the GReX signatures in disease-relevant tissues,
we used the TWAS method S-PrediXcan in this study (45).
We chose Multivariate adaptive shrinkage (Mashr) models
trained using the GTEx data (release v8) as the transcrip-
tome prediction models. For each GWAS dataset, we used S-
PrediXcan to impute GReX in the top 3 disease-relevant tis-
sues as determined by deTS. In addition, we imputed GReX in
the whole blood tissue for all diseases regardless of their tissue
specific context.
Connectivity methods and filtering criteria
We devised and implemented six distinct connectivity meth-
ods to infer drug candidates based on several previous bench-
mark and retrospective studies (13,46–48). They were the
Weighted Connectivity Score (WTCS), Connection Strength
Score (CSS), eXtreme Sum score (XSum) and three types of
correlation measurements (Spearman, Pearson and Cosine).
The method WTCS is used in CMap2.0 and employs the
Enrichment Score (ES) used in Gene Set Enrichment Analysis
(GSEA) (30). WTCS is defined as follows:
 compound-induced genes in the set XDownInDisease
(E Sup −E Sdown )  
WTCS = 2
, i f sign E Sup = sign (E Sdown )
0, otherwise
where E Sup and E Sdown are the ESs for upregulated and down-
regulated gene sets, respectively. The sizes of these gene sets are
uniformly defined as 50.
The method CSS measures the strength of the correlation
based on the signed ranks of genes in the disease signature and
the drug-induced signature. CSS had been shown to perform
superior to other methods when evaluated to assess drug–drug
similarities using L1000 data (46). CSS is defined as follows:
  NS 
 XSpearman: eXtreme Spearman rank correlation; XCosine:
css R, S = rabs
drug (gsi ) × signdrug (gsi )
i=1
 
css R, S
CSS =
cssmax (NR, NS )
where R  is the rank-ordered drug list, S is the unordered dis-
ease signature (50 upregulated genes and 50 downregulated
genes), NS is the number of genes in S that appears in R  , gsi is
the ith gene in the set S, rabs
drug
( gs i ) is the absolute-value-based
ranks of gsi in the drug profile, signdrug (gsi ) is the sign of gsi in
 , and NR is the number of genes in R
R  . To generate the non-
parametric P value of CSS, we randomly select NS genes in S
and perform 10 000 permutations.
The method XSum focuses on top- or bottom-ranked genes
and has been shown to perform better than other methods in
the inference of drug-indication using the CMap data (13).
The XSum score is defined as follows:
ChangeByCompound = top N upregulated ∪ top N down-
regulated genes (compound-treated versus no compound-
treated)
XUpInDisease = N disease-upregulated genes
∩ChangeByCompound
XDownInDisease = N disease-downregulated genes
∩ChangeByCompound
Sum(XUpInDisease) = sum of Z scores (level 5 data) of
compound-induced genes in the set XUpInDisease
Sum(XDownInDisease) = sum of Z scores (level 5 data) of
XSum = Sum(XUpInDisease) - Sum(XDownInDisease)
Similarly, we calculate the p value of XSum by 10 000 per-
mutations of XUpInDisease and XDownInDisease. In this
study, we set N to 50.
In addition, we calculate three metrics of correlation: Spear-
man Correlation Coefficient (SCC), Pearson Correlation Co-
efficient (PCC) and Cosine Correlation Score (CCS) using
all shared genes between drug-induced profiles and disease-
induced profiles. These three metrics can also be extended to
the extremely shared genes between the sets of genes most per-
turbed (50 upregulated genes + 50 downregulated genes) by
the drug and disease (XPearson: eXtreme Pearson correlation;
eXtreme Cosine correlation).
4 Nucleic Acids Research, 2023
With the results of all the six connectivity methods, we de-
fine the candidate disease-drug pairs to be included in our
database according to the following criteria:
WTCS < 0 & CSS < 0 & CSS p < 0.05 & XSum < 0 &
XSum p < 0.05 & SCC < 0 & PCC < 0 & CCS < 0.
Furthermore, to amalgamate the significance derived from
all six connectivity methods, we propose a meta-score calcu-
lated as the count of methods that identify the correlation with
high priority. Specifically, for each dataset-tissue pair, we rank
all candidate drugs by their scores from each method. A drug
is considered identified with high priority by a method if it is
ranked among the top 5% of all candidates by the correspond-
ing method. As a result, each drug receives 6 labels, each indi-
cating whether it is of high priority or not according to each
of the six methods. Notably, the range of the meta-score is
between 0 and 6 for a total of 6 methods.
Database implementation
PharmGWAS was deployed in a virtual machine with a Cen-
tOS 7.9 environment. Nginx v1.20.1 (https://nginx.org/en/)
was used as an HTTP and reverse proxy server. We used
MySQL (https://www.mysql.com) as the database engine. The
backend RESTful web service was built with Java Spring Boot
framework (https://spring.io/projects/spring-boot). The fron-
tend of the web interface was developed using React (https:
//reactjs.org) and organized using the UMI (https://umijs.org)
framework. For the user interface (UI) library, we chose Ant
Design (https://ant.design), which contained a set of high-
quality components that could be easily extended to build
rich and interactive user interfaces. In addition, the interac-
tive visualization of charts was achieved by using different li-
braries such as HighCharts (https://www.highcharts.com) and
ECharts (https://echarts.apache.org).
Database content and usage
Overview of PharmGWAS
PharmGWAS aims to translate GWAS signals into clini-
cal practice. Currently, PharmGWAS contains 1929 GWAS
datasets curated from GWAS Catalog, UKBB and several
large consortiums. Moreover, 720216 compound-perturbed
gene expression signatures were collected from CMap2.0 and
an additional 4269 perturbed signatures were collected from
GEO. We implemented our standard pipeline to infer candi-
date disease-drug pairs for each GWAS dataset. The outline
of PharmGWAS is illustrated in Figure 1. Currently, PharmG-
WAS deposits a total of 732947 genetically-informed disease-
drug pairs derived from CMap signatures and 7280 pairs from
GEO signatures, totaling 740227 (732947 + 7280) disease-
drug pairs. Among them, 81.58% (603 874) have a meta-score
of 0, 11.40% (84411) have a meta-score of 1, 3.52% (26 021)
have 2, 2.89% (21 370) have 3, 0.49% (3652) have 4, 838
have 5, and 61 have 6. In all web pages, the default rule for
sorting results is based on the meta-score in descending order.
To the best of our knowledge, PharmGWAS is the first system-
atic and comprehensive database to identify drug repurposing
candidates for nearly all available disease traits.
Web interface
PharmGWAS provides a user-friendly interface that allows
users to intuitively search, browse and download any results
in the database (Figure 2). The search function available in the
homepage supports keyword-based quick queries for multiple
forms of items, such as names of diseases, CMap signatures,
or GEO signatures (Figure 2A). Meanwhile, users can navigate
the entire database through three featured modules: Browse,
CMap Results and GEO Results. All processed data in Phar-
mGWAS are freely accessible.
The Browse module comprises three pages to facilitate ex-
ploration of GWAS datasets, CMap signatures and GEO sig-
natures. A series of extended interactive functional modules,
such as multi-criteria search and download, are designed to
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enable users to quickly retrieve relevant data of interest (Fig-
ure 2B). The Browse page of ‘GWAS datasets’ stores a large
amount of key meta information, including data source, dis-
ease name, publish year, the sample size of GWAS, the num-
ber of cases, the number of controls and so on. The Browse
pages of ‘CMap signatures’ and ‘GEO signatures’ also con-
tain a lot of meta information, such as signature name, mech-
anism of action (MOA), Canonical SMILES, InChiKey, cell
line, dose and GEO accession ID and so on. It is worth noting
that clicking on the corresponding ‘Dataset Name’ or ‘Sig-
nature ID’ button on the row of interest would direct users
to a new ‘detail page’ to view detailed results for a specific
GWAS dataset or signature. The detail page for a GWAS
dataset displays the meta-information about the study, the
disease-relevant tissues identified by deTS and the drug can-
didates derived from CMap signatures and GEO signatures
(Figure 2C). Furthermore, users can filter the results by en-
tering and selecting keywords about the tissue, CMap name,
or GEO accession ID. More explanatory information about
the column can be viewed by hovering over each entry of ta-
ble headers and clicking on the header will sort the table by
the selected column. By clicking on the ‘CMap Name’ col-
umn, users can access the details of the corresponding com-
pound in PubChem (49), such as chemical and physical prop-
erties, clinical trials, consolidated references, patents and so
on. By clicking on the ‘Association ID’ column, users will
be directed to a dedicated page with detailed results and
charts for the item (Figure 2C).
The ‘detail page’ about individual disease-drug pairs con-
tains five sections (Figure 2D). First, meta-information about
the corresponding disease and drug is shown at the top of the
page. Second, we use a radargram to provide an overview of
the results from all six connectivity methods. The larger the
area enclosed by the results of the six methods, the more reli-
able the drug candidate is. Third, to assess whether the disease-
upregulated genes appear toward the bottom of drug-induced
profiles and disease-downregulated genes appear toward the
top of drug-induced profiles, the GSEA plots of disease upreg-
ulated and downregulated genes in the pre-ranked list of drug
signature are provided. Next, the reverse intersection anal-
ysis of disease-upregulated genes with drug-downregulated
genes is illustrated in Venn diagrams, and similarly for disease-
downregulated genes with drug-upregulated genes. Finally,
the corresponding Z scores of upregulated and downregu-
lated genes in disease and drug signatures are displayed in the
histograms.
The modules for ‘CMap Results’ and ‘GEO Results’ pro-
vide an opportunity to directly search for disease-drug pairs
across datasets and signatures (Figure 2E). An advanced
search function has also been provided. Users can jump to
the detail page of disease-drug pairs by clicking on the ‘As-
Nucleic Acids Research, 2023 5

GWA
W S Summary Statistics Connectivity Map GEO

TSEA

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Disease-relevant Tissues

TWAS

Disease Gene
Expression Signatures Drug-induced Expression Signatures

Connectivity Methods

WTCS CSS XSum Spearman Pearson Cosine

Genetically-informed Drug Candidates

Figure 1. Schematic overview of PharmGWAS. TSEA: Tissue-Specific Enrichment Analysis. TWAS: Transcriptome Wide Association Studies. GEO: Gene
Expression Omnibus. WTCS: Weighted Connectivity Score. CSS: Connection Strength Score. XSum: The eXtreme Sum score.

sociation ID’ in the CMap Results and GEO Results pages. In
addition, all processed results can be freely downloaded.
Application of PharmGWAS: coronary artery
disease as an example
We take the GWAS dataset of coronary artery disease (CAD)
reported by Webb et al. (50) as a case study to demonstrate the
application of PharmGWAS (Figure 2C and D). CAD is a lead-
ing cause of death worldwide with a major heritable compo-
nent and GWAS has identified ∼60 loci explaining ∼15% of
the heritability. The three tissues mostly associated with CAD
as determined by using MAGMA and deTS were artery coro-
nary (P = 0.0070), liver (P = 0.0242) and spleen (P = 0.0242).
We calculated GReX in these three tissues as well as in the
whole blood. After connectivity analyses with CMap2.0 sig-
natures, the top-ranked drug candidate was lisofylline (WTCS
= −0.5730, XSum = −9.3722, XSum P < 1 × 10−5 , CSS =
−0.1464, CSS P = 0.0101, SCC = −0.1478, PCC = −0.1996,
CCS = −0.1998) in artery coronary (Figure 2C). Lisofylline
was originally designed as an anti-inflammatory agent and
had been investigated for the therapy of diabetes (51). It had
been reported to have suppressive effects on the serum-free
fatty acids (52), a risk factor of atherosclerosis and atheroscle-
rosis was a major complication of diabetes (53). Besides, pen-
toxifylline, a methylxanthine derivative of lisofylline, had been
proven to have therapeutic benefits on atherosclerosis (54).
Taken together, lisofylline is a reliable candidate drug for the
treatment of CAD. These results suggested PharmGWAS could
serve as a valuable resource for drug repurposing by leverag-
ing the discovery power of human genetics data.
Discussion and future developments
In this study, we developed PharmGWAS, a GWAS-based
knowledgebase for drug repurposing by incorporating hu-
man genetics data and drug perturbation data. To the best
of our knowledge, PharmGWAS is the first valuable refer-
ence resource that provides the analysis results processed by a
unified drug repurposing workflow for thousands of publicly
available disease-relevant GWAS datasets. In addition to the
wide range of disease types covered by GWAS datasets from
multiple sources, the drug perturbation data retrieved from
CMap2.0 and the GEO RNA-seq signatures extracted from
SigCom LINCS are among the most comprehensive. Our re-
sults shed new light on drug discovery, drug combination, drug
resistance and drug side effects from the human genetics per-
spective.
With the accumulation of new GWAS datasets with increas-
ing amounts of samples, PharmGWAS will be continuously
updated by collecting and processing the latest available ge-
6 Nucleic Acids Research, 2023

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Figure 2. Screenshots of the major web pages for PharmGWAS. (A) The homepage search function allows users to quickly query for multiple items
including GWAS datasets, CMap signatures and GEO signatures. (B) The browse module provides multi-criteria search function to further filter the data
of interest. (C) Detailed browse page for an individual GWAS dataset. Clicking on the ‘Association ID’ will direct users to view the detailed results and
charts for corresponding item and clicking on the ‘CMap Name’ will lead to the PubChem for specific information. (D) The detail results page for each
candidate disease–drug pair. (E) The CMap Results and GEO Results modules.
Nucleic Acids Research, 2023
netic data. In particular, our results are restricted solely to sci-
entific studies and do not constitute any clinical recommen-
dations. Because of the varying quality of the GWAS datasets
and imputed GReX, caution is required in interpreting our re-
sults. Moreover, because CMap data are limited to a selection
of cell lines rather than tissues, further efforts to expand the
repertoire of tissues will enhance the reliability of our results.
Lastly, population-scale applications of single-cell sequencing
is becoming possible with the development of single-cell se-
quencing technology and decreasing costs (55–57). Thus, we
anticipate that our framework for drug repurposing based on
the TWAS concept will expand at single-cell resolution in the
future.
Data availability
PharmGWAS is available at https://ngdc.cncb.ac.cn/
pharmgwas. Users can freely access all processed data
and results through the web service.
Acknowledgements
We thank National Genomics Data Center (NGDC) for pro-
viding support in database deployment. We are grateful to all
members of the Laboratory for Precision Health (LPH) for
their valuable comments.
Funding
National Natural Science Foundation of China [32270706];
Strategic Priority Research Program of the Chinese Academy
of Sciences [XDB38010400]; Startup Research Fund of
Henan Academy of Sciences [232016009]. Funding for open
access charge: National Natural Science Foundation of China
[32270706] and Strategic Priority Research Program of Chi-
nese Academy of Sciences [XDB38010400 to P.J.].
Conflict of interest statement
None declared.
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