OBJECTIVE The 2-year risk of psychosis in persons who meet research criteria for a high-risk syndrome is about 15%-25%; improvements in risk prediction accuracy would benefit the development and implementation of preventive interventions. The authors sought to assess polygenic risk score (PRS) prediction of subsequent psychosis in persons at high risk and to determine the impact of adding the PRS to a previously validated psychosis risk calculator. METHODS Persons meeting research criteria for psychosis high risk (N=764) and unaffected individuals (N=279) were followed for up to 2 years. The PRS was based on the latest schizophrenia and bipolar genome-wide association studies. Variables in the psychosis risk calculator included stressful life events, trauma, disordered thought content, verbal learning, information processing speed, and family history of psychosis. RESULTS For Europeans, the PRS varied significantly by group and was higher in the psychosis converter group compared with both the nonconverter and unaffected groups, but was similar for the nonconverter group compared with the unaffected group. For non-Europeans, the PRS varied significantly by group; the difference between the converters and nonconverters was not significant, but the PRS was significantly higher in converters than in unaffected individuals, and it did not differ between nonconverters and unaffected individuals. The R2liability (R2 adjusted for the rate of disease risk in the population being studied, here assuming a 2-year psychosis risk between 10% and 30%) for Europeans varied between 9.2% and 12.3% and for non-Europeans between 3.5% and 4.8%. The amount of risk prediction information contributed by the addition of the PRS to the risk calculator was less than severity of disordered thoughts and similar to or greater than for other variables. For Europeans, the PRS was correlated with risk calculator variables of information processing speed and verbal memory. CONCLUSIONS The PRS discriminates psychosis converters from nonconverters and modestly improves individualized psychosis risk prediction when added to a psychosis risk calculator. The schizophrenia PRS shows promise in enhancing risk prediction in persons at high risk for psychosis, although its potential utility is limited by poor performance in persons of non-European ancestry.

中文翻译：

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多基因风险评分对临床高危人群目标人群精神病预测的贡献。

目标 符合高危综合征研究标准的人的 2 年精神病风险约为 15%-25%；风险预测准确性的提高将有利于预防性干预措施的制定和实施。作者试图评估多基因风险评分 (PRS) 对高危人群后续精神病的预测，并确定将 PRS 添加到先前验证的精神病风险计算器的影响。方法 对符合精神病高风险研究标准的人（N=764）和未受影响的人（N=279）进行长达 2 年的随访。PRS 基于最新的精神分裂症和双极全基因组关联研究。精神病风险计算器中的变量包括压力性生活事件、创伤、思维内容混乱、语言学习、信息处理速度、和精神病家族史。结果 对于欧洲人来说，不同组的 PRS 差异显着，与未转变者组和未受影响组相比，精神病转变者组的 PRS 较高，但与未受影响组相比，未转变者组的 PRS 相似。对于非欧洲人，PRS 因群体而异；转化者和非转化者之间的差异不显着，但转化者的 PRS 显着高于未受影响的个体，并且在非转化者和未受影响的个体之间没有差异。欧洲人的 R2 负债率（根据所研究人群的疾病风险率调整后的 R2，这里假设 2 年精神病风险在 10% 和 30% 之间）在 9.2% 和 12.3% 之间，非欧洲人在 3.5% 和 3.5% 之间。 4.8%。通过将 PRS 添加到风险计算器中所贡献的风险预测信息量低于思维混乱的严重程度，并且与其他变量相似或更大。对于欧洲人，PRS 与信息处理速度和语言记忆的风险计算器变量相关。结论 PRS 将精神病转化者与非转化者区分开来，并在添加到精神病风险计算器时适度提高个体化精神病风险预测。精神分裂症 PRS 在提高精神病高风险人群的风险预测方面显示出希望，尽管其潜在效用受到非欧洲血统人群表现不佳的限制。对于欧洲人，PRS 与信息处理速度和语言记忆的风险计算器变量相关。结论 PRS 将精神病转化者与非转化者区分开来，并在添加到精神病风险计算器时适度提高个体化精神病风险预测。精神分裂症 PRS 在提高精神病高风险人群的风险预测方面显示出希望，尽管其潜在效用受到非欧洲血统人群表现不佳的限制。对于欧洲人，PRS 与信息处理速度和语言记忆的风险计算器变量相关。结论 PRS 将精神病转化者与非转化者区分开来，并在添加到精神病风险计算器时适度提高个体化精神病风险预测。精神分裂症 PRS 在提高精神病高风险人群的风险预测方面显示出希望，尽管其潜在效用受到非欧洲血统人群表现不佳的限制。