How people undergoing genomic sequencing interpret and react to varied secondary findings with limited actionability

To investigate patient reactions to and understanding of secondary genomic findings with limited to no medical actionability (LMA-SFs) from diagnostic genome sequencing. We analyzed LMA-SFs returned to 47 adults who elected to receive a broad set of these results from 6 categories. Findings indicated elevated risk (reportable/positive) or not (negative/normal). Most participants (<i>N</i> = 43) also completed surveys to report their distress, decision regret, expected health anxiety, and whether and how they perceived results as reassuring or troubling. Most participants received some reportable LMA-SFs for common risk, pharmacogenetic, and carrier status variants. Fewer received reportable <i>APOE</i> haplotype or monogenetic condition variants. None received results indicating high risk for severe neurological disease. Overall, participants (76.7% female, 97.7% White) had low distress, decision regret, and expected health anxiety. None described negative/normal findings as troubling. However, their interpretations of reportable/positive results varied. Even within the same result type, some participants found them troubling, while others found them reassuring based on their perception of the results’ utility. Participants’ short-term well-being was not reduced by receiving LMA-SFs. Their interpretations suggested varied personal utilities and the need for post-test resources to aid understanding of these types of results and their health significance. Genomic sequencing can find a diagnosis for people who have symptoms that suggest they may have a hereditary disease. It can also find results that do not change medical treatment for most people. This study looks at whether people feel distressed when they get secondary findings that will give them little to no medically useful information. Because these findings can be hard to understand, we also asked people to explain what their findings meant to them. We found that learning these findings did not make people feel distressed. Also, people who received the same or similar results felt differently about the results they received. Some felt their results were good news, while others were worried. Even when they learned about higher health risk, some people felt it was useful because it helps them plan. In sum, we found NO/LITTLE evidence that secondary findings caused distress in patients. We should learn more about how personal understanding influences future health decisions.

本研究旨在探究患者对诊断性基因组测序所得的医学可操作性有限或无医学可操作性的次要基因组发现（secondary genomic findings with limited to no medical actionability, LMA-SFs）的反应与认知。我们分析了47名自愿接收6大类共多项此类检出结果的成年受试者所获的LMA-SFs。此类结果分为两类：提示风险升高（可报告/阳性）与未提示风险（阴性/正常）。多数受试者（N=43）还完成了调查问卷，用以评估其心理痛苦程度、决策后悔感、预期健康焦虑水平，以及他们如何将该结果感知为安心提示或困扰来源。
多数受试者获得了针对常见风险、药物基因组学及携带者状态变异的可报告LMA-SFs；少数受试者获得了可报告的APOE单倍型或单基因疾病相关变异。无受试者获得提示重度神经系统疾病高风险的检出结果。
整体而言，受试者中女性占比76.7%，白人占比97.7%，其心理痛苦、决策后悔感与预期健康焦虑水平均较低。无受试者将阴性/正常结果视为困扰来源，但受试者对可报告/阳性结果的解读存在差异。即便针对同一类结果，部分受试者认为其带来困扰，而另一部分受试者则因感知到结果的实用价值而感到安心。接收LMA-SFs并未降低受试者的短期幸福感。受试者的不同解读反映出其个体实用价值感知存在差异，同时也提示亟需检测后支持资源，以帮助受试者理解此类结果及其健康意义。
基因组测序可为存在疑似遗传性疾病症状的患者明确诊断，但同时也可能检出对多数患者而言不会改变临床诊疗方案的结果。本研究聚焦于：当患者获得几乎无医学实用价值的次要基因组发现时，是否会产生心理痛苦。鉴于此类结果往往难以理解，本研究同时要求受试者阐释其对自身检出结果的认知。
研究结果显示，获知此类结果并未导致受试者产生心理痛苦。此外，即便接收了相同或相似结果的受试者，对其检出结果的感受也存在差异：部分受试者认为这是好消息，而另一部分则感到担忧。即便获知自身健康风险升高，部分受试者仍认为此类结果具有实用价值，因其可帮助其进行健康规划。
综上，本研究未发现或仅发现极少证据表明次要基因组发现会引发患者心理痛苦。未来仍需进一步探究个体认知如何影响其后续健康决策。