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Polygenic Risk Prediction in Diverticulitis.
De Roo, Ana C; Chen, Yanhua; Du, Xiaomeng; Handelman, Samuel; Byrnes, Mary; Regenbogen, Scott E; Speliotes, Elizabeth K; Maguire, Lillias H.
Afiliação
  • De Roo AC; Department of Surgery, University of Michigan, Ann Arbor, MI.
  • Chen Y; Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI.
  • Du X; Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI.
  • Handelman S; Eli Lilly and Company, Indianapolis, IN.
  • Byrnes M; Department of Surgery, University of Michigan, Ann Arbor, MI.
  • Regenbogen SE; Department of Surgery, University of Michigan, Ann Arbor, MI.
  • Speliotes EK; Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI.
  • Maguire LH; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI.
Ann Surg ; 277(6): e1262-e1268, 2023 06 01.
Article em En | MEDLINE | ID: mdl-35876359
OBJECTIVE: To derive and validate a polygenic risk score (PRS) to predict the occurrence and severity of diverticulitis and to understand the potential for incorporation of a PRS in current decision-making. BACKGROUND: PRS quantifies genetic variation into a continuous measure of risk. There is a need for improved risk stratification to guide surgical decision-making that could be fulfilled by PRS. It is unknown how surgeons might integrate PRS in decision-making. METHODS: We derived a PRS with 44 single-nucleotide polymorphisms associated with diverticular disease in the UK Biobank and validated this score in the Michigan Genomics Initiative (MGI). We performed a discrete choice experiment of practicing colorectal surgeons. Surgeons rated the influence of clinical factors and a hypothetical polygenic risk prediction tool. RESULTS: Among 2812 MGI participants with diverticular disease, 1964 were asymptomatic, 574 had mild disease, and 274 had severe disease. PRS was associated with occurrence and severity. Patients in the highest PRS decile were more likely to have diverticulitis [odds ratio (OR)=1.84; 95% confidence interval (CI), 1.42-2.38)] and more likely to have severe diverticulitis (OR=1.61; 95% CI, 1.04-2.51) than the bottom 50%. Among 213 surveyed surgeons, extreme disease-specific factors had the largest utility (3 episodes in the last year, +74.4; percutaneous drain, + 69.4). Factors with strongest influence against surgery included 1 lifetime episode (-63.3), outpatient management (-54.9), and patient preference (-39.6). PRS was predicted to have high utility (+71). CONCLUSIONS: A PRS derived from a large national biobank was externally validated, and found to be associated with the incidence and severity of diverticulitis. Surgeons have clear guidance at clinical extremes, but demonstrate equipoise in intermediate scenarios. Surgeons are receptive to PRS, which may be most useful in marginal clinical situations. Given the current lack of accurate prognostication in recurrent diverticulitis, PRS may provide a novel approach for improving patient counseling and decision-making.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Diverticulite Tipo de estudo: Etiology_studies / Guideline / Prognostic_studies / Qualitative_research / Risk_factors_studies Limite: Humans País como assunto: America do norte Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Diverticulite Tipo de estudo: Etiology_studies / Guideline / Prognostic_studies / Qualitative_research / Risk_factors_studies Limite: Humans País como assunto: America do norte Idioma: En Ano de publicação: 2023 Tipo de documento: Article