Last updated: 2024-05-28

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Knit directory: multigroup_ctwas_analysis/

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Overview

Traits

aFib, IBD, LDL, SBP, SCZ, WBC

details

Tissues

The independent tissues are selected by single tissue analysis

Omics

eQTL, sQTL weights are from GTEx PredictDB

apaQTL wetights are from https://www.nature.com/articles/s41467-024-46064-7#Sec2. Top 10 SNPs with largest abs(weights) were selected after harmonization

Settings

  1. Weight processing:

PredictDB:

  • drop_strand_ambig = TRUE,
  • scale_by_ld_variance = TRUE,
  • load_predictdb_LD = T,

FUSION:

  • method_FUSION = “enet”,
  • fusion_top_n_snps = 10,
  • drop_strand_ambig = TRUE,
  • scale_by_ld_variance = F,
  • load_predictdb_LD = F,
  1. Parameter estimation and fine-mapping
  • niter_prefit = 5,
  • niter = 60,
  • L = 3,
  • group_prior_var_structure = “shared_type”,
  • maxSNP = 20000,
  • min_nonSNP_PIP = 0.5,

Results

Results from multi-group analysis

The results are summarized by

  1. Heritability contribution by contexts: we aggregate the PVE values by omics and tissues, making it easier to understand the distribution of PVE across different genetic contexts.

  2. Combined PIP by omics: we aggregate the Susie PIPs by omics

  3. Combined PIP by contexts: we aggregate the Susie PIPs by tissues, making it easier to understand the distribution of PIP across different genetic contexts.

  4. Specific molecular traits of top genes: we creates a pie chart to visualize the proportion of genes classified into different categories based on their PIPs contributed by each genetics contexts. The categories are based on the proportion of each QTL type relative to the combined PIP value:

  • by eQTL: Number of genes where the ratio of eQTL to combined PIP is greater than 0.8.
  • by sQTL: Number of genes where the ratio of sQTL to combined PIP is greater than 0.8.
  • by apaQTL: Number of genes where the ratio of apaQTL to combined PIP is greater than 0.8.
  • by sQTL+apaQTL: Number of genes where the combined ratio of apaQTL and sQTL to combined PIP is greater than 0.8, but neither apaQTL nor sQTL individually exceed 0.8.
  • unspecified: Number of genes not classified into any of the above categories.

Comparing with single group eQTL results

Please not that the ealier single group eQTL analyses were performed under L=5 but the current analyses were under L=3

We compared number of significant genes, overlapping genes and the changes in PVE for eQTLs across five tissues reported by single eQTL analysi

aFib

TO DO

IBD

Results from multi-group analysis

Version Author Date
4f4541b XSun 2024-05-27

Comparing with single group eQTL results

[1] "the top tissues from single group analyses are Cells_Cultured_fibroblasts,Whole_Blood,Adipose_Subcutaneous,Esophagus_Mucosa,Heart_Left_Ventricle"

LDL

Results from multi-group analysis

Version Author Date
d7e59bb XSun 2024-05-27
4f4541b XSun 2024-05-27

Comparing with single group eQTL results

[1] "the top tissues from single group analyses are Liver,Spleen,Adipose_Subcutaneous,Adrenal_Gland,Esophagus_Mucosa"

SBP

Results from multi-group analysis

Version Author Date
d7e59bb XSun 2024-05-27
4f4541b XSun 2024-05-27

Comparing with single group eQTL results

[1] "the top tissues from single group analyses are Artery_Tibial,Adipose_Subcutaneous,Brain_Cortex,Heart_Left_Ventricle,Spleen"

SCZ

Results from multi-group analysis

Version Author Date
d7e59bb XSun 2024-05-27

Comparing with single group eQTL results

[1] "the top tissues from single group analyses are Heart_Left_Ventricle,Adrenal_Gland,Artery_Coronary,Brain_Cerebellum,Stomach"

WBC

Results from multi-group analysis

Version Author Date
d7e59bb XSun 2024-05-27

Comparing with single group eQTL results

[1] "the top tissues from single group analyses are Whole_Blood,Adipose_Subcutaneous,Artery_Aorta,Skin_Sun_Exposed_Lower_leg,Spleen"

sessionInfo()
R version 4.2.0 (2022-04-22)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: CentOS Linux 7 (Core)

Matrix products: default
BLAS/LAPACK: /software/openblas-0.3.13-el7-x86_64/lib/libopenblas_haswellp-r0.3.13.so

locale:
[1] C

attached base packages:
[1] stats     graphics  grDevices utils     datasets  methods   base     

other attached packages:
 [1] RColorBrewer_1.1-3 forcats_0.5.1      stringr_1.5.1      dplyr_1.1.4       
 [5] purrr_1.0.2        readr_2.1.2        tidyr_1.3.0        tibble_3.2.1      
 [9] ggplot2_3.5.1      tidyverse_1.3.1    data.table_1.14.2  ctwas_0.2.1.9000  

loaded via a namespace (and not attached):
  [1] colorspace_2.0-3            rjson_0.2.21               
  [3] ellipsis_0.3.2              rprojroot_2.0.3            
  [5] XVector_0.36.0              locuszoomr_0.2.1           
  [7] GenomicRanges_1.48.0        fs_1.5.2                   
  [9] rstudioapi_0.13             farver_2.1.0               
 [11] DT_0.22                     ggrepel_0.9.1              
 [13] bit64_4.0.5                 lubridate_1.8.0            
 [15] AnnotationDbi_1.58.0        fansi_1.0.3                
 [17] xml2_1.3.3                  codetools_0.2-18           
 [19] logging_0.10-108            cachem_1.0.6               
 [21] knitr_1.39                  jsonlite_1.8.0             
 [23] workflowr_1.7.0             Rsamtools_2.12.0           
 [25] broom_0.8.0                 dbplyr_2.1.1               
 [27] png_0.1-7                   compiler_4.2.0             
 [29] httr_1.4.3                  backports_1.4.1            
 [31] assertthat_0.2.1            Matrix_1.5-3               
 [33] fastmap_1.1.0               lazyeval_0.2.2             
 [35] cli_3.6.1                   later_1.3.0                
 [37] htmltools_0.5.2             prettyunits_1.1.1          
 [39] tools_4.2.0                 gtable_0.3.0               
 [41] glue_1.6.2                  GenomeInfoDbData_1.2.8     
 [43] rappdirs_0.3.3              Rcpp_1.0.8.3               
 [45] Biobase_2.56.0              cellranger_1.1.0           
 [47] jquerylib_0.1.4             vctrs_0.6.5                
 [49] Biostrings_2.64.0           rtracklayer_1.56.0         
 [51] crosstalk_1.2.0             xfun_0.41                  
 [53] rvest_1.0.2                 lifecycle_1.0.4            
 [55] irlba_2.3.5                 restfulr_0.0.14            
 [57] ensembldb_2.20.2            XML_3.99-0.14              
 [59] zlibbioc_1.42.0             zoo_1.8-10                 
 [61] scales_1.3.0                gggrid_0.2-0               
 [63] hms_1.1.1                   promises_1.2.0.1           
 [65] MatrixGenerics_1.8.0        ProtGenerics_1.28.0        
 [67] parallel_4.2.0              SummarizedExperiment_1.26.1
 [69] AnnotationFilter_1.20.0     LDlinkR_1.2.3              
 [71] yaml_2.3.5                  curl_4.3.2                 
 [73] memoise_2.0.1               sass_0.4.1                 
 [75] biomaRt_2.54.1              stringi_1.7.6              
 [77] RSQLite_2.3.1               highr_0.9                  
 [79] S4Vectors_0.34.0            BiocIO_1.6.0               
 [81] GenomicFeatures_1.48.3      BiocGenerics_0.42.0        
 [83] filelock_1.0.2              BiocParallel_1.30.3        
 [85] GenomeInfoDb_1.39.9         rlang_1.1.2                
 [87] pkgconfig_2.0.3             matrixStats_0.62.0         
 [89] bitops_1.0-7                evaluate_0.15              
 [91] lattice_0.20-45             labeling_0.4.2             
 [93] GenomicAlignments_1.32.0    htmlwidgets_1.5.4          
 [95] cowplot_1.1.1               bit_4.0.4                  
 [97] tidyselect_1.2.0            plyr_1.8.7                 
 [99] magrittr_2.0.3              R6_2.5.1                   
[101] IRanges_2.30.0              generics_0.1.2             
[103] DelayedArray_0.22.0         DBI_1.2.2                  
[105] withr_2.5.0                 haven_2.5.0                
[107] pgenlibr_0.3.3              pillar_1.9.0               
[109] whisker_0.4                 KEGGREST_1.36.3            
[111] RCurl_1.98-1.7              mixsqp_0.3-43              
[113] modelr_0.1.8                crayon_1.5.1               
[115] utf8_1.2.2                  BiocFileCache_2.4.0        
[117] plotly_4.10.0               tzdb_0.4.0                 
[119] rmarkdown_2.25              progress_1.2.2             
[121] readxl_1.4.0                grid_4.2.0                 
[123] blob_1.2.3                  git2r_0.30.1               
[125] reprex_2.0.1                digest_0.6.29              
[127] httpuv_1.6.5                stats4_4.2.0               
[129] munsell_0.5.0               viridisLite_0.4.0          
[131] bslib_0.3.1