Department of Surgery, University of Michigan, Ann Arbor, MI.
Division of Gastroenterology and Hepatology, University of Michigan Health System, Ann Arbor, MI.
Ann Surg. 2023 Jun 1;277(6):e1262-e1268. doi: 10.1097/SLA.0000000000005623. Epub 2022 Jul 25.
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.
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.
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.
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).
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.
推导并验证一种多基因风险评分（PRS），以预测憩室炎的发生和严重程度，并了解将 PRS 纳入当前决策的潜力。
PRS 将遗传变异量化为风险的连续衡量标准。需要改进风险分层来指导可能通过 PRS 实现的手术决策。尚不清楚外科医生如何将 PRS 纳入决策。
我们使用英国生物银行中与憩室疾病相关的 44 个单核苷酸多态性推导了一个 PRS，并在密歇根基因组倡议（MGI）中对该评分进行了验证。我们对进行了结肠直肠外科医生的离散选择实验。外科医生对临床因素和假设的多基因风险预测工具的影响进行了评分。
在 2812 名患有憩室疾病的 MGI 参与者中，1964 名无症状，574 名轻度疾病，274 名患有严重疾病。PRS 与发病和严重程度相关。PRS 最高十分位数的患者更有可能患憩室炎[比值比（OR）=1.84；95%置信区间（CI），1.42-2.38)]，并且更有可能患有严重憩室炎（OR=1.61；95%CI，1.04-2.51) 比底部 50%。在接受调查的 213 名外科医生中，极端疾病特异性因素具有最大的效用（过去一年中 3 次发作，+74.4；经皮引流，+69.4）。对手术影响最大的因素包括 1 次终生发作（-63.3）、门诊治疗（-54.9）和患者偏好（-39.6）。PRS 预计将具有较高的效用（+71）。
从大型国家生物库中推导的 PRS 经过外部验证，与憩室炎的发生和严重程度相关。外科医生在临床极端情况下有明确的指导，但在中间情况下表现出均衡。外科医生对 PRS 持接受态度，这可能在边缘临床情况下最有用。鉴于目前在复发性憩室炎中缺乏准确的预后预测，PRS 可能为改善患者咨询和决策提供一种新方法。
