Contents

1 Introduction

This R package provides access to the Qtlizer web server. Qtlizer annotates lists of common small variants (mainly SNPs) and genes in humans with associated changes in gene expression using the most comprehensive database of published quantitative trait loci (QTLs).

2 Installation

if(!requireNamespace("BiocManager", quietly = TRUE))
    install.packages("BiocManager")
BiocManager::install("Qtlizer")

3 Loading package

library(Qtlizer)
#> 
#>   ---------
#>   
#>   For example usage please run: vignette('Qtlizer')
#>   
#>   Web-based GUI: http://genehopper.de/qtlizer
#>   Documentation: http://genehopper.de/help#qtlizer_docu
#>   Github Repo: https://github.com/matmu/Qtlizer
#>   
#>   Citation appreciated:
#>   Munz M, Wohlers I, Simon E, Reinberger T, Busch H, Schaefer A and Erdmann J (2020) Qtlizer: comprehensive QTL annotation of GWAS results. Scientific Reports. doi:10.1038/s41598-020-75770-7
#>   
#>   ---------

4 Example function calls

The Qtlizer database can be queried with the function get_qtls. Accepted query terms are variant and gene identifiers of the form

# Call get_qtls with a variant as a single query term
get_qtls("rs4284742")
#> 1 unique query term(s) found
#> Retrieving QTL information from Qtlizer...
#> 10 data point(s) received
#>    query_type query_term  sentinel proxy_variant corr ld_method corr_thr chr
#> 1     Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#> 2     Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#> 3     Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#> 4     Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#> 5     Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#> 6     Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#> 7     Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#> 8     Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#> 9     Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#> 10    Variant  rs4284742 rs4284742          <NA> <NA>      <NA>     <NA>  19
#>    var_pos_hg19 var_pos_hg38 type     gene          ensgid colocalization
#> 1      52131733     51628480 eQTL   SHANK1 ENSG00000161681          trans
#> 2      52131733     51628480 eQTL     CD33 ENSG00000105383            cis
#> 3      52131733     51628480 eQTL  SIGLEC5 ENSG00000105501            cis
#> 4      52131733     51628480 eQTL  SIGLEC5 ENSG00000105501            cis
#> 5      52131733     51628480 eQTL  RPL9P33 ENSG00000244071            cis
#> 6      52131733     51628480 eQTL SIGLEC14 ENSG00000254415            cis
#> 7      52131733     51628480 eQTL   ZNF813 ENSG00000198346          trans
#> 8      52131733     51628480 eQTL   NDUFA3 ENSG00000170906          trans
#> 9      52131733     51628480 eQTL     SYT5 ENSG00000129990          trans
#> 10     52131733     51628480 eQTL   ZNF787 ENSG00000142409          trans
#>    distance                            tissue       p       sign_info      beta
#> 1     909.0                            Spleen 6.9e-07          FDR<5% -0.394972
#> 2     384.6 Cells - Lymphoblastoid cell lines 1.2e-01 Q-value; FDR<5%      <NA>
#> 3       0.0                  Peripheral blood 7.7e-14          FDR<5%      <NA>
#> 4       0.0                       Whole blood 3.3e-05          FDR<5%   -0.1105
#> 5       6.8                       Whole blood 2.2e-06          FDR<5% -0.181466
#> 6      14.1                         Pituitary 2.0e-05          FDR<5% -0.297989
#> 7    1839.3                Brain - Cerebellum 4.5e-03         FWER<5%      <NA>
#> 8    2474.2             Brain - Parietal lobe 4.3e-03         FWER<5%      <NA>
#> 9    3542.7             Brain - Parietal lobe 8.7e-03         FWER<5%      <NA>
#> 10   4458.9             Brain - Parietal lobe 6.4e-03         FWER<5%      <NA>
#>      ea  nea             source          pmid is_sign is_best n_qtls n_best
#> 1     G    A            GTEx v8 PMID:23715323    true    true      1      1
#> 2  <NA> <NA>             seeQTL PMID:22171328   false   false      8      0
#> 3     A    G Blood eQTL Browser PMID:24013639    true   false    151      0
#> 4     G    A            GTEx v8 PMID:23715323    true   false     87      0
#> 5     G    A            GTEx v8 PMID:23715323    true   false     31      0
#> 6     G    A            GTEx v8 PMID:23715323    true   false     32      0
#> 7  <NA> <NA>             ScanDB PMID:19933162   false   false     18      0
#> 8  <NA> <NA>             ScanDB PMID:19933162   false   false      8      0
#> 9  <NA> <NA>             ScanDB PMID:19933162   false   false      9      0
#> 10 <NA> <NA>             ScanDB PMID:19933162   false   false     21      0
#>    n_sw_sign n_occ
#> 1          1     1
#> 2          0     1
#> 3          2     2
#> 4          2     2
#> 5          1     1
#> 6          1     1
#> 7          0     1
#> 8          0     1
#> 9          0     1
#> 10         0     1

Common seperators (space, comma, space + comma, …) are accepted. Multiple terms can be passed in a single string, each term separated by comma, whitespace or both:

# Call get_qtls with multiple query terms in single string
df = get_qtls("rs4284742, rs2070901")
#> 2 unique query term(s) found
#> Retrieving QTL information from Qtlizer...
#> 45 data point(s) received

Alternatively, terms can be passed as a vector:

# Call get_qtls with multiple query terms as vector
df = get_qtls(c("rs4284742", "DEFA1"))
#> 2 unique query term(s) found
#> Retrieving QTL information from Qtlizer...
#> 221 data point(s) received

Input variants can be enriched by variants in linkage disequilibrium (LD). The correlation method to be used can be set with ld_method. Default is “r2”, alternatively “dprime” can be used. The correlation threshold, above which other correlated variants should be included, can be set with corr and ranges between 0 and 1. Default is “NA”

# Use parameters corr and ld_method
df = get_qtls(c("rs4284742", "DEFA1"), corr = 0.8, ld_method = "r2")
#> 2 unique query term(s) found
#> Retrieving QTL information from Qtlizer...
#> 221 data point(s) received

Also, column descriptions can be viewed:

# View meta info
df = get_qtls("rs4284742")
#> 1 unique query term(s) found
#> Retrieving QTL information from Qtlizer...
#> 10 data point(s) received
comment(df)
#>  [1] "# query_type:Query type"                                                                                                                              
#>  [2] "# query_term:Query term"                                                                                                                              
#>  [3] "# sentinel:Index variant"                                                                                                                             
#>  [4] "# chr: Chromosome name of sentinel/proxy variant on reference genome"                                                                                 
#>  [5] "# var_pos_hg19: Position of sentinel (or proxy if defined) variant on reference genome hg19"                                                          
#>  [6] "# var_pos_hg38: Position of sentinel (or proxy if defined) variant on reference genome hg38"                                                          
#>  [7] "# type:QTL type"                                                                                                                                      
#>  [8] "# gene:Gene"                                                                                                                                          
#>  [9] "# ensgid:Ensembl Gene ID"                                                                                                                             
#> [10] "# colocalization:Co-localization;Cis indicates, if index/proxy variant and gene are located in the same topologically associated domain, trans if not"
#> [11] "# distance:Distance;Distance between index/proxy variant and gene in kilobases"                                                                       
#> [12] "# tissue:Tissue"                                                                                                                                      
#> [13] "# p:P-value"                                                                                                                                          
#> [14] "# sign_info:Significance info"                                                                                                                        
#> [15] "# beta:Beta;Effect size and direction with respect to effect allele"                                                                                  
#> [16] "# ea:EA;Effect allele"                                                                                                                                
#> [17] "# nea:NEA;Non-effect allele"                                                                                                                          
#> [18] "# source:Source"                                                                                                                                      
#> [19] "# pmid:PMID"                                                                                                                                          
#> [20] "# is_sign:Is sign"                                                                                                                                    
#> [21] "# is_best:Is best"                                                                                                                                    
#> [22] "# n_qtls:N QTLs"                                                                                                                                      
#> [23] "# n_best:N best"                                                                                                                                      
#> [24] "# n_sign:N sign"                                                                                                                                      
#> [25] "# n_occ:N occ"

The QTL results is returned as data frame by default or as GenomicRanges::GRanges object. To return the results as GenomicRanges::GRanges object, return_obj is set to “granges”. If return_obj is set to “granges”, parameter ref_version sets the reference version in which the GRange object is returned. Allowed values are “hg19” (GRCh37) by default and “hg38” (GRCh38).

# Return result as GRange object with ref_version hg38
granges = get_qtls("rs4284742", return_obj = "granges", ref_version = "hg38")
#> 1 unique query term(s) found
#> Retrieving QTL information from Qtlizer...
#> 10 data point(s) received

5 Output of Session Info

The output of sessionInfo() on the system on which this document was compiled:

sessionInfo()
#> R Under development (unstable) (2022-10-25 r83175)
#> Platform: x86_64-pc-linux-gnu (64-bit)
#> Running under: Ubuntu 22.04.1 LTS
#> 
#> Matrix products: default
#> BLAS:   /home/biocbuild/bbs-3.17-bioc/R/lib/libRblas.so
#> LAPACK: /usr/lib/x86_64-linux-gnu/lapack/liblapack.so.3.10.0
#> 
#> locale:
#>  [1] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
#>  [3] LC_TIME=en_GB              LC_COLLATE=C              
#>  [5] LC_MONETARY=en_US.UTF-8    LC_MESSAGES=en_US.UTF-8   
#>  [7] LC_PAPER=en_US.UTF-8       LC_NAME=C                 
#>  [9] LC_ADDRESS=C               LC_TELEPHONE=C            
#> [11] LC_MEASUREMENT=en_US.UTF-8 LC_IDENTIFICATION=C       
#> 
#> attached base packages:
#> [1] stats     graphics  grDevices utils     datasets  methods   base     
#> 
#> other attached packages:
#> [1] Qtlizer_1.13.0   BiocStyle_2.27.0
#> 
#> loaded via a namespace (and not attached):
#>  [1] httr_1.4.4             cli_3.4.1              knitr_1.40            
#>  [4] rlang_1.0.6            xfun_0.34              stringi_1.7.8         
#>  [7] jsonlite_1.8.3         S4Vectors_0.37.0       RCurl_1.98-1.9        
#> [10] htmltools_0.5.3        sass_0.4.2             stats4_4.3.0          
#> [13] rmarkdown_2.17         evaluate_0.17          jquerylib_0.1.4       
#> [16] bitops_1.0-7           fastmap_1.1.0          GenomeInfoDb_1.35.0   
#> [19] IRanges_2.33.0         yaml_2.3.6             bookdown_0.29         
#> [22] BiocManager_1.30.19    stringr_1.4.1          compiler_4.3.0        
#> [25] XVector_0.39.0         digest_0.6.30          R6_2.5.1              
#> [28] GenomeInfoDbData_1.2.9 curl_4.3.3             GenomicRanges_1.51.0  
#> [31] magrittr_2.0.3         bslib_0.4.0            tools_4.3.0           
#> [34] zlibbioc_1.45.0        BiocGenerics_0.45.0    cachem_1.0.6