重大精神疾病的多基因风险评分的低稳定性和特异性限制了它们的临床实用性
Josephine Mollon1, Laura M Schultz2, Emma E M Knowles1
1Department of Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Biological psychiatry
|March 20, 2025
概括
多基因风险评分 (PRSs) 在主要抑郁症,酒精使用障碍,2型糖尿病和精神分裂症的不同措施中显示出有限的稳定性和低的特异性. 这些发现表明,目前PRS在精神病学应用中缺乏临床实用性.
科学领域:
- 遗传学和生物信息学 遗传学和生物信息学
- 精神疾病 精神疾病
- 精准医学是一门精准的医学.
背景情况:
- 关于多基因风险评分 (PRS) 的稳定性和有效性的研究有限.
- 评估一个PRS确定为高风险的个体是否被另一个PRS一致识别至关重要.
- 评估高风险状态与实际疾病患病率之间的关联对于PRS实用性至关重要.
研究的目的:
- 检查多基因风险评分 (PRSs) 对主要抑郁症 (MDD),酒精使用障碍 (AUD),2型糖尿病 (T2D) 和精神分裂症 (SCZ) 的稳定性和有效性.
- 确定同一疾病的不同PRS中高风险个体识别的一致性.
- 评估PRS对这些条件的预测准确性 (灵敏度和特异性).
主要方法:
- 利用了来自408,853名英国白人 (年龄在37-73岁之间) 的英国生物库数据.
- 使用PRS连续收缩 (CS) 计算了MDD,AUD,T2D和SCZ的多个PRS.
- 通过相关性和一致的高风险识别 (前5%);通过敏感性和特异性评估有效性.
主要成果:
- PRS的稳定性各不相同,同一疾病的不同PRS之间存在低至高的相关性.
- 在所有疾病中,对高风险个体 (前5%) 的一致识别通常低于50%.
- 敏感度为中度至良好,但所有PRS的特异性始终低 (50.7%-56.4%).
结论:
- 该研究强调了当前PRS的有限稳定性和低特异性.
- 这些局限性表明,目前PRS在精神病学实践中缺乏足够的临床实用性.
- 需要进一步开发以提高PRS在临床应用中的可靠性和准确性.
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