Last updated: 2025-09-08

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Knit directory: genomics_ancest_disease_dispar/

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Rmd b209d1f IJbeasley 2025-09-05 Even more trait collapsing

1 Set up

library(dplyr)
library(data.table)
library(ggplot2)
library(stringr)
gwas_study_info <- fread(here::here("output/gwas_study_info_trait_ontology_info.csv"))

2 Initial summary

2.1 Objectives of this analysis:

  • Collapsing and standardizing disease trait terms in GWAS study metadata without relying on ontology mappings.
  • Initial harmonization of disease trait terms (fixing spelling, collapsing studies that study different aspects of the same disease)

3 Number of studies per trait - before any grouping

Let’s look at the number of studies associated with each unique disease/trait term before any grouping or collapsing.

n_studies_trait = gwas_study_info |>
  dplyr::filter(DISEASE_STUDY == T) |>
  dplyr::select(all_disease_terms, PUBMED_ID) |>
  dplyr::distinct() |>
  dplyr::group_by(all_disease_terms) |>
  dplyr::summarise(n_studies = dplyr::n()) |>
  dplyr::arrange(desc(n_studies))

head(n_studies_trait)
# A tibble: 6 × 2
  all_disease_terms         n_studies
  <chr>                         <int>
1 type 2 diabetes mellitus        148
2 major depressive disorder       110
3 alzheimer disease               108
4 schizophrenia                   102
5 breast carcinoma                101
6 asthma                          100
dim(n_studies_trait)
[1] 2709    2

4 Disease trait collapsing and cleaning

# Basic cleaning of disease terms
# Removes trailing commas, 
gwas_study_info$all_disease_terms = sub(",$", "", gwas_study_info$all_disease_terms)

# trims whitespace
gwas_study_info$all_disease_terms = stringr::str_trim(gwas_study_info$all_disease_terms)

# remove apostrophes
gwas_study_info$all_disease_terms = stringr::str_remove_all(gwas_study_info$all_disease_terms, "'|’")

# initializes a new column (collected_all_disease_terms) to standardized traits
# collapse more traits 
gwas_study_info = gwas_study_info |> 
  mutate(collected_all_disease_terms = all_disease_terms)

4.1 Where a study investigates a given aspect of of disease, reduce this to a study of this disease

4.1.1 e.g Susceptibility to X measurement, X disorder measurement etc.

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
        str_replace(collected_all_disease_terms, 
                    "^susceptibility to (.*?) measurement$", "\\1")

         ) |>
    mutate(collected_all_disease_terms = 
        str_replace(collected_all_disease_terms, 
                    "^susceptibility to (.*?) (.*?) measurement$", "\\1")

         ) |>
      mutate(collected_all_disease_terms = 
        str_replace(collected_all_disease_terms, 
                    "^susceptibility to (.*?) (.*?) infection$", "\\1")

         ) 


gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
        str_replace(collected_all_disease_terms, 
                    "susceptibility to viral and mycobacterial infections",
                    "viral and mycobacterial infections")

         ) |>
    mutate(collected_all_disease_terms = 
        str_replace(collected_all_disease_terms, 
                    "susceptibility to strep throat",
                    "strep throat")
         )




gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
          stringr::str_remove(collected_all_disease_terms, " symptom severity measurement")
         ) |>
  mutate(collected_all_disease_terms = 
          stringr::str_remove(collected_all_disease_terms, " severity measurement| exacerbation measurement")
         ) 



gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms =
           str_replace_all(collected_all_disease_terms,
                           "\\bdependence\\s+measurement\\b",
                           "dependence")) |> 
  mutate(collected_all_disease_terms =
           str_replace_all(collected_all_disease_terms,
                           "\\ballergy\\s+measurement\\b",
                           "allergy")) |> 
  mutate(collected_all_disease_terms =
           str_replace_all(collected_all_disease_terms,
                           "\\baddiction\\s+measurement\\b",
                           "addiction")) |> 
      mutate(collected_all_disease_terms =
           str_replace_all(collected_all_disease_terms,
                           "\\bsyndrome\\s+measurement\\b",
                           "syndrome")) |> 
      mutate(collected_all_disease_terms =
           str_replace_all(collected_all_disease_terms,
                           "\\bdisorder\\s+measurement\\b",
                           "disorder"))

4.1.2 e.g age of onset of

gwas_study_info = gwas_study_info |>
      mutate(collected_all_disease_terms = 
         stringr::str_remove(collected_all_disease_terms,
                         pattern = "age of onset of "))


gwas_study_info = 
gwas_study_info |> 
 mutate(collected_all_disease_terms  = 
          stringr::str_replace_all(collected_all_disease_terms ,
                                  pattern = "age of onset of type 2 diabetes mellitus",
                                   "type 2 diabetes mellitus"
                          )  
        )

4.1.3 e.g. Family history of

gwas_study_info = gwas_study_info |>
      mutate(collected_all_disease_terms = 
         stringr::str_remove(collected_all_disease_terms,
                         pattern = "family history of "))


gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "family history of alzheimer’s disease",
                          "alzheimers disease"
         ))

4.1.4 Time to remission

4.1.4.1 COVID

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "time to remission of covid-19 symptoms",
                          "covid-19"
         ))

4.1.5 Symptom measurement

4.1.5.1 ADHD

gwas_study_info = gwas_study_info |> 
  mutate(collected_all_disease_terms = 
           stringr::str_replace_all(collected_all_disease_terms,
                            "adhd symptom measurement",
                            "adhd")
         )

4.1.5.2 Agoraphobia

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "agoraphobia symptom measurement",
                          "agoraphobia"
         ))

4.1.5.3 Alzheimer’s disease - neuropathological change

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "alzheimer disease neuropathological",
                          "alzheimers disease"
         ))

4.1.5.4 Asthma

gwas_study_info = gwas_study_info |> 
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "asthma exacerbation measurement",
                          "asthma"
         )) |>
  mutate(collected_all_disease_terms = 
           stringr::str_replace_all(collected_all_disease_terms,
                            "asthma symptoms measurement",
                            "asthma"
           ))

4.1.5.5 COVID symptoms

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "covid-19 symptoms measurement",
                          "covid-19")
  )

4.1.5.6 Irritable bowel syndrome

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "irritable bowel syndrome symptom measurement",
                          "irritable bowel syndrome"
         ))

4.1.6 Obsessive compulsive disorder

4.1.6.1 Parkinson’s disease

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "parkinsons disease symptom measurement",
                          "parkinsons disease"
         ))

4.1.6.2 PTSD

gwas_study_info = gwas_study_info |> 
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "post-traumatic stress disorder symptom measurement",
                          "post-traumatic stress disorder"
         ))

4.1.6.3 Respiratory symptom change

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "respiratory symptom change measurement" ,
                          "respiratory symptom measurement" 
         ))

4.1.7 Measurement

4.1.7.1 Anxiety disorder

gwas_study_info = gwas_study_info |> 
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "anxiety disorder measurement",
                          "anxiety disorder"
         ))

4.1.7.2 Coronary atherosclerosis

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "coronary atherosclerosis measurement",
                          "coronary atherosclerosis")
  )

4.1.8 Insommnia

gwas_study_info = gwas_study_info |> 
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "insomnia measurement",
                          "insomnia"
         ))

4.1.8.1 Lewy body dementia

gwas_study_info = gwas_study_info |> 
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "lewy body dementia measurement",
                          "lewy body dementia"
         ))

4.1.8.2 Psychosis predisposition

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
        stringr::str_replace_all(collected_all_disease_terms,
                         "psychosis predisposition measurement",
                         "psychosis predisposition")
        )

4.1.8.3 Sleep apnea measurement

gwas_study_info = gwas_study_info |>
        mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "sleep apnea measurement",
                          "sleep apnea"
         ))

4.1.8.4 Susceptibility to infectious disease

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
        str_replace(collected_all_disease_terms, 
                    "susceptibility to infectious disease measurement",
                    "susceptibility to infectious disease")
         )

4.1.9 Substance abuse measurement

4.1.9.1 Alcohol

gwas_study_info = gwas_study_info |> 
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "alcohol dependence measurement",
                          "alcohol dependence"
         ))

4.1.9.2 Cannibis

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "cannabis dependence measurement",
                          "cannabis dependence"
         ))

4.1.9.3 Cocaine

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "cocaine use disorder|cocaine dependence",
                          "cocaine-related disorders"
         ))

4.1.9.4 Nicotine

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "nicotine dependence symptom count",
                          "nicotine dependence"
         ))

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "nicotine withdrawal symptom count|nicotine withdrawal measurement",
                          "nicotine withdrawal"
         ))

4.2 Deal with basic synonyms

4.2.1 Carcinoma = Cancer

gwas_study_info = gwas_study_info |>
      mutate(collected_all_disease_terms = 
           stringr::str_replace_all(collected_all_disease_terms,
                            "\\bcarcinoma",
                            "cancer")
         )

gwas_study_info = gwas_study_info |>
      mutate(collected_all_disease_terms = 
           stringr::str_replace_all(collected_all_disease_terms,
                            "triple-negative breast cancer",
                            "breast cancer"
           ))

4.2.2 Coronary artery disease = coronary atherosclerosis

https://www.ebi.ac.uk/ols4/ontologies/efo/classes/http%253A%252F%252Fwww.ebi.ac.uk%252Fefo%252FEFO_0001645

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "coronary atherosclerosis",
                          "coronary artery disease"
         ))

4.2.3 Head and neck cancer = head and neck malignant neoplasia

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "head and neck malignant neoplasia",
                          "head and neck cancer"
         ))

4.2.4 Hepatitis virus infection = hepatitis infection

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "hepatitis a virus infection",
                          "hepatitis a infection"
         )) |>
      mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "hepatitis b virus infection",
                          "hepatitis b infection"
         )) |>
        mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "hepatitis c virus infection",
                          "hepatitis c infection"
         ))

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "chronic hepatitis c virus infection",
                          "chronic hepatitis, hepatitis c infection"
         )) |>
      mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "chronic hepatitis b virus infection",
                          "chronic hepatitis, hepatitis b infection"
         ))

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "hepatitis virus-related liver cancer",
                          "hepatitis, liver cancer"
         ))

4.2.5 HIV

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "hiv-1 infection",
                          "hiv infection"
         ))

4.2.6 Mumps virus infection = mumps

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "mumps virus infectious disease",
                          "mumps"
         ))

4.2.7 Renal cancer = kidney cancer

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "renal cancer",
                          "kidney cancer"
         ))

4.2.8 Rubella infect = rubella

gwas_study_info = gwas_study_info |>
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "rubella infection",
                          "rubella"
         ))
gwas_study_info = gwas_study_info |> 
    mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "multiple sclerosis symptom measurement",
                          "multiple sclerosis"
         ))

4.2.9 Autism = Autism Spectrum Disorder = Asperger Syndrome

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
        stringr::str_replace_all(collected_all_disease_terms,
                         "autism spectrum disorder",
                         "autism")
        ) |>
    mutate(collected_all_disease_terms = 
        stringr::str_replace_all(collected_all_disease_terms,
                         "asperger syndrome",
                         "autism")
        )

4.3 Type 1 diabetes = type 1 diabetes mellitus

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
        stringr::str_replace_all(collected_all_disease_terms,
                         "type 1 diabetes mellitus",
                         "type 1 diabetes")
        ) |>
    mutate(collected_all_disease_terms = 
        stringr::str_replace_all(collected_all_disease_terms,
                         "type 1 diabetes",
                         "type 1 diabetes mellitus")
        )

4.3.1 ADHD = attention deficit hyperactivity disorder

gwas_study_info = gwas_study_info |> 
    mutate(collected_all_disease_terms = 
           stringr::str_replace_all(collected_all_disease_terms,
                            "attention deficit hyperactivity disorder",
                            "adhd"
         ))

4.4 Narcolepsy = Narcolepsy without cataplexy

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms = 
         stringr::str_replace_all(collected_all_disease_terms,
                          "narcolepsy without cataplexy",
                          "narcolepsy"
         ))

4.5 Typos

4.5.1 Alzheimer -> alzheimers

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms =
         stringr::str_replace_all(collected_all_disease_terms,
                          "alzheimer disease",
                          "alzheimers disease"
         ))

4.5.2 Parkinson -> parkinsons

gwas_study_info = gwas_study_info |>
  mutate(collected_all_disease_terms =
         stringr::str_replace_all(collected_all_disease_terms,
                          "parkinson disease",
                          "parkinsons disease"
         ))

5 Putting it all together

gwas_study_info = gwas_study_info |>
  rowwise() |>
  mutate(
    collected_all_disease_terms = paste0(
      unique(unlist(stringr::str_split(collected_all_disease_terms, ", "))),
      collapse = ", "
    )
  ) |>
  ungroup()

           
gwas_study_info$collected_all_disease_terms = stringr::str_trim(gwas_study_info$collected_all_disease_terms)
gwas_study_info$collected_all_disease_terms = sub(",$", "", gwas_study_info$collected_all_disease_terms)

5.1 Final summary - number of studies per trait - after harmonization

n_studies_trait = gwas_study_info |>
  dplyr::filter(DISEASE_STUDY == T) |>
  dplyr::select(collected_all_disease_terms, PUBMED_ID) |>
  dplyr::distinct() |>
  dplyr::group_by(collected_all_disease_terms) |>
  dplyr::summarise(n_studies = dplyr::n()) |>
  dplyr::arrange(desc(n_studies))

head(n_studies_trait)
# A tibble: 6 × 2
  collected_all_disease_terms n_studies
  <chr>                           <int>
1 type 2 diabetes mellitus          149
2 alzheimers disease                117
3 breast cancer                     115
4 asthma                            111
5 major depressive disorder         110
6 schizophrenia                     106
dim(n_studies_trait)
[1] 2602    2
diseases <- stringr::str_split(pattern = ", ", 
                               gwas_study_info$collected_all_disease_terms)  |> 
            unlist() |>
            stringr::str_trim()

length(unique(diseases))
[1] 1832

5.1.1 Save the updated gwas_study_info with harmonized disease terms

gwas_study_info <- fwrite(gwas_study_info,
                          here::here("output/gwas_study_info_trait_ontology_info.csv"))

sessionInfo()
R version 4.3.1 (2023-06-16)
Platform: aarch64-apple-darwin20 (64-bit)
Running under: macOS 15.6.1

Matrix products: default
BLAS:   /Library/Frameworks/R.framework/Versions/4.3-arm64/Resources/lib/libRblas.0.dylib 
LAPACK: /Library/Frameworks/R.framework/Versions/4.3-arm64/Resources/lib/libRlapack.dylib;  LAPACK version 3.11.0

locale:
[1] en_US.UTF-8/en_US.UTF-8/en_US.UTF-8/C/en_US.UTF-8/en_US.UTF-8

time zone: America/Los_Angeles
tzcode source: internal

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

other attached packages:
[1] stringr_1.5.1     ggplot2_3.5.2     data.table_1.17.8 dplyr_1.1.4      
[5] workflowr_1.7.1  

loaded via a namespace (and not attached):
 [1] gtable_0.3.6       jsonlite_2.0.0     compiler_4.3.1     renv_1.0.3        
 [5] promises_1.3.3     tidyselect_1.2.1   Rcpp_1.1.0         git2r_0.36.2      
 [9] callr_3.7.6        later_1.4.2        jquerylib_0.1.4    scales_1.4.0      
[13] yaml_2.3.10        fastmap_1.2.0      here_1.0.1         R6_2.6.1          
[17] generics_0.1.4     knitr_1.50         tibble_3.3.0       rprojroot_2.1.0   
[21] RColorBrewer_1.1-3 bslib_0.9.0        pillar_1.11.0      rlang_1.1.6       
[25] utf8_1.2.6         cachem_1.1.0       stringi_1.8.7      httpuv_1.6.16     
[29] xfun_0.52          getPass_0.2-4      fs_1.6.6           sass_0.4.10       
[33] cli_3.6.5          withr_3.0.2        magrittr_2.0.3     ps_1.9.1          
[37] grid_4.3.1         digest_0.6.37      processx_3.8.6     rstudioapi_0.17.1 
[41] lifecycle_1.0.4    vctrs_0.6.5        evaluate_1.0.4     glue_1.8.0        
[45] farver_2.1.2       whisker_0.4.1      rmarkdown_2.29     httr_1.4.7        
[49] tools_4.3.1        pkgconfig_2.0.3    htmltools_0.5.8.1