Multi-ancestry genome- and phenome-wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm.
<h4>Objective</h4>Diverticular disease (DD) is one of the most prevalent conditions encountered by gastroenterologists, affecting ~50% of Americans before the age of 60. Our aim was to identify genetic risk variants and clinical phenotypes associated with DD, leveraging multiple electron...
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2023-01-01
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| author | Yoonjung Yoonie Joo Jennifer A Pacheco William K Thompson Laura J Rasmussen-Torvik Luke V Rasmussen Frederick T J Lin Mariza de Andrade Kenneth M Borthwick Erwin Bottinger Andrew Cagan David S Carrell Joshua C Denny Stephen B Ellis Omri Gottesman James G Linneman Jyotishman Pathak Peggy L Peissig Ning Shang Gerard Tromp Annapoorani Veerappan Maureen E Smith Rex L Chisholm Andrew J Gawron M Geoffrey Hayes Abel N Kho |
| author_facet | Yoonjung Yoonie Joo Jennifer A Pacheco William K Thompson Laura J Rasmussen-Torvik Luke V Rasmussen Frederick T J Lin Mariza de Andrade Kenneth M Borthwick Erwin Bottinger Andrew Cagan David S Carrell Joshua C Denny Stephen B Ellis Omri Gottesman James G Linneman Jyotishman Pathak Peggy L Peissig Ning Shang Gerard Tromp Annapoorani Veerappan Maureen E Smith Rex L Chisholm Andrew J Gawron M Geoffrey Hayes Abel N Kho |
| author_sort | Yoonjung Yoonie Joo |
| collection | DOAJ |
| description | <h4>Objective</h4>Diverticular disease (DD) is one of the most prevalent conditions encountered by gastroenterologists, affecting ~50% of Americans before the age of 60. Our aim was to identify genetic risk variants and clinical phenotypes associated with DD, leveraging multiple electronic health record (EHR) data sources of 91,166 multi-ancestry participants with a Natural Language Processing (NLP) technique.<h4>Materials and methods</h4>We developed a NLP-enriched phenotyping algorithm that incorporated colonoscopy or abdominal imaging reports to identify patients with diverticulosis and diverticulitis from multicenter EHRs. We performed genome-wide association studies (GWAS) of DD in European, African and multi-ancestry participants, followed by phenome-wide association studies (PheWAS) of the risk variants to identify their potential comorbid/pleiotropic effects in clinical phenotypes.<h4>Results</h4>Our developed algorithm showed a significant improvement in patient classification performance for DD analysis (algorithm PPVs ≥ 0.94), with up to a 3.5 fold increase in terms of the number of identified patients than the traditional method. Ancestry-stratified analyses of diverticulosis and diverticulitis of the identified subjects replicated the well-established associations between ARHGAP15 loci with DD, showing overall intensified GWAS signals in diverticulitis patients compared to diverticulosis patients. Our PheWAS analyses identified significant associations between the DD GWAS variants and circulatory system, genitourinary, and neoplastic EHR phenotypes.<h4>Discussion</h4>As the first multi-ancestry GWAS-PheWAS study, we showcased that heterogenous EHR data can be mapped through an integrative analytical pipeline and reveal significant genotype-phenotype associations with clinical interpretation.<h4>Conclusion</h4>A systematic framework to process unstructured EHR data with NLP could advance a deep and scalable phenotyping for better patient identification and facilitate etiological investigation of a disease with multilayered data. |
| format | Article |
| id | doaj-art-78f28682110648cfbe41e76d4bf5e28c |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-78f28682110648cfbe41e76d4bf5e28c2025-08-20T02:36:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01185e028355310.1371/journal.pone.0283553Multi-ancestry genome- and phenome-wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm.Yoonjung Yoonie JooJennifer A PachecoWilliam K ThompsonLaura J Rasmussen-TorvikLuke V RasmussenFrederick T J LinMariza de AndradeKenneth M BorthwickErwin BottingerAndrew CaganDavid S CarrellJoshua C DennyStephen B EllisOmri GottesmanJames G LinnemanJyotishman PathakPeggy L PeissigNing ShangGerard TrompAnnapoorani VeerappanMaureen E SmithRex L ChisholmAndrew J GawronM Geoffrey HayesAbel N Kho<h4>Objective</h4>Diverticular disease (DD) is one of the most prevalent conditions encountered by gastroenterologists, affecting ~50% of Americans before the age of 60. Our aim was to identify genetic risk variants and clinical phenotypes associated with DD, leveraging multiple electronic health record (EHR) data sources of 91,166 multi-ancestry participants with a Natural Language Processing (NLP) technique.<h4>Materials and methods</h4>We developed a NLP-enriched phenotyping algorithm that incorporated colonoscopy or abdominal imaging reports to identify patients with diverticulosis and diverticulitis from multicenter EHRs. We performed genome-wide association studies (GWAS) of DD in European, African and multi-ancestry participants, followed by phenome-wide association studies (PheWAS) of the risk variants to identify their potential comorbid/pleiotropic effects in clinical phenotypes.<h4>Results</h4>Our developed algorithm showed a significant improvement in patient classification performance for DD analysis (algorithm PPVs ≥ 0.94), with up to a 3.5 fold increase in terms of the number of identified patients than the traditional method. Ancestry-stratified analyses of diverticulosis and diverticulitis of the identified subjects replicated the well-established associations between ARHGAP15 loci with DD, showing overall intensified GWAS signals in diverticulitis patients compared to diverticulosis patients. Our PheWAS analyses identified significant associations between the DD GWAS variants and circulatory system, genitourinary, and neoplastic EHR phenotypes.<h4>Discussion</h4>As the first multi-ancestry GWAS-PheWAS study, we showcased that heterogenous EHR data can be mapped through an integrative analytical pipeline and reveal significant genotype-phenotype associations with clinical interpretation.<h4>Conclusion</h4>A systematic framework to process unstructured EHR data with NLP could advance a deep and scalable phenotyping for better patient identification and facilitate etiological investigation of a disease with multilayered data.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0283553&type=printable |
| spellingShingle | Yoonjung Yoonie Joo Jennifer A Pacheco William K Thompson Laura J Rasmussen-Torvik Luke V Rasmussen Frederick T J Lin Mariza de Andrade Kenneth M Borthwick Erwin Bottinger Andrew Cagan David S Carrell Joshua C Denny Stephen B Ellis Omri Gottesman James G Linneman Jyotishman Pathak Peggy L Peissig Ning Shang Gerard Tromp Annapoorani Veerappan Maureen E Smith Rex L Chisholm Andrew J Gawron M Geoffrey Hayes Abel N Kho Multi-ancestry genome- and phenome-wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm. PLoS ONE |
| title | Multi-ancestry genome- and phenome-wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm. |
| title_full | Multi-ancestry genome- and phenome-wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm. |
| title_fullStr | Multi-ancestry genome- and phenome-wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm. |
| title_full_unstemmed | Multi-ancestry genome- and phenome-wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm. |
| title_short | Multi-ancestry genome- and phenome-wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm. |
| title_sort | multi ancestry genome and phenome wide association studies of diverticular disease in electronic health records with natural language processing enriched phenotyping algorithm |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0283553&type=printable |
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