Last updated: 2024-11-24

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Knit directory: multigroup_ctwas_analysis/

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Fusion Lasso model of DNA methylation

I built lasso model of DNA methylation with FUSION for Whole Blood and Colon Transverse. Similar to meQTL mapping, for each CpG site, I extracted surrounding 50kb genptypes and train lasso models with cross validation. With heritability cutoff p<0.0001, I have about 16,000 and 48,000 CpG sites in whole blood and colon transverse. Among which, 5,000 and 40,000 CpG sites are also in QTL mapping. Colon have more overlaps than whole blood. The average cross-validation R2 for lasso in whole blood and colon transverse are 0.393 and 0.248 In the single QTL approach (qval < 0.001), we have 7,720 and 91,466 CpG sites.

Version Author Date
c3e7a9f sq-96 2024-10-25
919465c sq-96 2024-10-23

IBD results

cTWAS parameters with methylation lasso models (50kb, h2 pvalue<0.00001)

Version Author Date
c3e7a9f sq-96 2024-10-25
f8b659f sq-96 2024-10-23
b3ff842 sq-96 2024-10-23
919465c sq-96 2024-10-23

Percent of heritability with methylation lasso models

Version Author Date
c3e7a9f sq-96 2024-10-25
2db1bdc sq-96 2024-10-23
919465c sq-96 2024-10-23

Top cTWAS genes with methylation lasso models

2024-11-24 12:02:38 INFO::Annotating susie alpha result ...
2024-11-24 12:02:38 INFO::Map molecular traits to genes
2024-11-24 12:02:39 INFO::Split PIPs for molecular traits mapped to multiple genes

Top cTWAS genes from single tissue models

2024-11-24 12:03:21 INFO::Annotating fine-mapping result ...
2024-11-24 12:03:21 INFO::Map molecular traits to genes
2024-11-24 12:03:27 INFO::Add gene positions
2024-11-24 12:03:27 INFO::Add SNP positions
2024-11-24 12:04:01 INFO::Annotating fine-mapping result ...
2024-11-24 12:04:01 INFO::Map molecular traits to genes
2024-11-24 12:04:02 INFO::Split PIPs for molecular traits mapped to multiple genes
2024-11-24 12:04:03 INFO::Add gene positions
2024-11-24 12:04:04 INFO::Add SNP positions
2024-11-24 12:04:27 INFO::Annotating fine-mapping result ...
2024-11-24 12:04:27 INFO::Map molecular traits to genes
2024-11-24 12:04:29 INFO::Add gene positions
2024-11-24 12:04:30 INFO::Add SNP positions
2024-11-24 12:04:55 INFO::Annotating fine-mapping result ...
2024-11-24 12:04:55 INFO::Map molecular traits to genes
2024-11-24 12:04:55 INFO::Split PIPs for molecular traits mapped to multiple genes
2024-11-24 12:04:57 INFO::Add gene positions
2024-11-24 12:04:58 INFO::Add SNP positions

2024-11-24 12:05:16 INFO::Annotating susie alpha result ...
2024-11-24 12:05:16 INFO::Map molecular traits to genes
2024-11-24 12:05:16 INFO::Split PIPs for molecular traits mapped to multiple genes
2024-11-24 12:05:23 INFO::Annotating susie alpha result ...
2024-11-24 12:05:23 INFO::Map molecular traits to genes
2024-11-24 12:05:30 INFO::Annotating susie alpha result ...
2024-11-24 12:05:30 INFO::Map molecular traits to genes
2024-11-24 12:05:31 INFO::Split PIPs for molecular traits mapped to multiple genes

Adding meQTL to eQTL identifies an additional 11 high PIP genes

Version Author Date
c3e7a9f sq-96 2024-10-25

Adding eQTL to meQTL identifies an additional 16 high PIP genes

  1. 12/17 meQTL genes still have combined PIP > 0.8 after adding eQTL
  2. 3/17 meQTL genes have decreased combined PIP < 0.8 after adding eQTL
  3. 2/17 meQTL genes are lost, due to region selection after adding eQTL
  4. Among the 12 overalpped genes:
  • One gene (BRD7) is mediation (meQTL pip decreases from 0.96 to 0.09, eQTL pip=0.90).
  • Two genes (TNFSF15 and ATG16L1) are competition (eQTL pip = 0.2 and meQTL pip is decreased by 0.2).
  • Nine genes are meQTL alone (no eQTL pip).

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] LC_CTYPE=en_US.UTF-8       LC_NUMERIC=C              
 [3] LC_TIME=en_US.UTF-8        LC_COLLATE=en_US.UTF-8    
 [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] grid      stats     graphics  grDevices utils     datasets  methods  
[8] base     

other attached packages:
 [1] VennDiagram_1.7.3   futile.logger_1.4.3 RColorBrewer_1.1-3 
 [4] pheatmap_1.0.12     magrittr_2.0.3      RSQLite_2.3.7      
 [7] lubridate_1.9.3     forcats_1.0.0       stringr_1.5.1      
[10] dplyr_1.1.4         purrr_1.0.2         readr_2.1.5        
[13] tidyr_1.3.1         tibble_3.2.1        tidyverse_2.0.0    
[16] ctwas_0.4.15        data.table_1.16.0   gridExtra_2.3      
[19] ggVennDiagram_1.5.2 ggplot2_3.5.1       workflowr_1.7.0    

loaded via a namespace (and not attached):
  [1] BiocFileCache_2.6.1         lazyeval_0.2.2             
  [3] crosstalk_1.2.1             BiocParallel_1.32.6        
  [5] GenomeInfoDb_1.34.9         LDlinkR_1.4.0              
  [7] digest_0.6.37               yulab.utils_0.1.7          
  [9] ensembldb_2.22.0            htmltools_0.5.8.1          
 [11] fansi_1.0.6                 memoise_2.0.1              
 [13] tzdb_0.4.0                  Biostrings_2.66.0          
 [15] matrixStats_1.4.1           locuszoomr_0.3.5           
 [17] timechange_0.3.0            prettyunits_1.2.0          
 [19] colorspace_2.1-1            blob_1.2.4                 
 [21] rappdirs_0.3.3              ggrepel_0.9.6              
 [23] xfun_0.47                   callr_3.7.2                
 [25] crayon_1.5.3                RCurl_1.98-1.16            
 [27] jsonlite_1.8.9              zoo_1.8-12                 
 [29] glue_1.7.0                  gtable_0.3.5               
 [31] zlibbioc_1.44.0             XVector_0.38.0             
 [33] DelayedArray_0.24.0         BiocGenerics_0.44.0        
 [35] scales_1.3.0                futile.options_1.0.1       
 [37] DBI_1.2.3                   Rcpp_1.0.13                
 [39] viridisLite_0.4.2           progress_1.2.3             
 [41] gridGraphics_0.5-1          bit_4.5.0                  
 [43] DT_0.22                     stats4_4.2.0               
 [45] htmlwidgets_1.6.4           httr_1.4.7                 
 [47] pkgconfig_2.0.3             XML_3.99-0.14              
 [49] farver_2.1.2                sass_0.4.9                 
 [51] dbplyr_2.5.0                utf8_1.2.4                 
 [53] ggplotify_0.1.2             tidyselect_1.2.1           
 [55] labeling_0.4.3              rlang_1.1.4                
 [57] later_1.3.2                 AnnotationDbi_1.60.2       
 [59] munsell_0.5.1               pgenlibr_0.3.7             
 [61] tools_4.2.0                 cachem_1.1.0               
 [63] cli_3.6.3                   generics_0.1.3             
 [65] evaluate_1.0.0              fastmap_1.2.0              
 [67] yaml_2.3.10                 processx_3.7.0             
 [69] knitr_1.48                  bit64_4.5.2                
 [71] fs_1.6.4                    KEGGREST_1.38.0            
 [73] AnnotationFilter_1.22.0     whisker_0.4                
 [75] formatR_1.14                aplot_0.2.3                
 [77] xml2_1.3.3                  biomaRt_2.54.1             
 [79] compiler_4.2.0              rstudioapi_0.14            
 [81] plotly_4.10.4               filelock_1.0.3             
 [83] curl_5.2.3                  png_0.1-7                  
 [85] bslib_0.8.0                 stringi_1.8.4              
 [87] highr_0.11                  ps_1.7.1                   
 [89] GenomicFeatures_1.50.4      lattice_0.20-45            
 [91] ProtGenerics_1.30.0         Matrix_1.5-3               
 [93] vctrs_0.6.5                 pillar_1.9.0               
 [95] lifecycle_1.0.4             jquerylib_0.1.4            
 [97] cowplot_1.1.3               bitops_1.0-8               
 [99] irlba_2.3.5.1               httpuv_1.6.5               
[101] patchwork_1.3.0             rtracklayer_1.58.0         
[103] GenomicRanges_1.50.2        R6_2.5.1                   
[105] BiocIO_1.8.0                promises_1.3.0             
[107] IRanges_2.32.0              codetools_0.2-18           
[109] lambda.r_1.2.4              SummarizedExperiment_1.28.0
[111] rprojroot_2.0.3             rjson_0.2.23               
[113] withr_3.0.1                 GenomicAlignments_1.34.1   
[115] Rsamtools_2.14.0            S4Vectors_0.36.2           
[117] GenomeInfoDbData_1.2.9      parallel_4.2.0             
[119] hms_1.1.3                   ggfun_0.1.6                
[121] gggrid_0.2-0                rmarkdown_2.28             
[123] MatrixGenerics_1.10.0       logging_0.10-108           
[125] git2r_0.30.1                mixsqp_0.3-54              
[127] getPass_0.2-2               Biobase_2.58.0             
[129] restfulr_0.0.15