Polygenic Scores and Onset of Major Mood or Psychotic Disorders Among Offspring of Affected Parents.
Polygenic Scores and Onset of Major Mood or Psychotic Disorders Among Offspring of Affected Parents.
复制标题
受影响父母的后代的多基因评分和主要情绪或精神障碍的发作。
DOI：
10.1176/appi.ajp.20220476
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Sugranye
中科院分区：
文献类型：
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作者：
Zwicker,Alyson;Fullerton,JaniceM;Mullins,Niamh;Rice,Frances;Hafeman,DanellaM;vanHaren,NeeltjeEM;Setiaman,Nikita;Merranko,JohnA;Goldstein,BenjaminI;Ferrera,AlessandraG;Stapp,EmmaK;delaSerna,Elena;Moreno,Dolores;Sugranye
家族史是精神疾病的既定危险因素。作者试图调查是否多基因评分（PGSs）可以补充家族史，以提高识别风险的主要情绪和精神病disorders.MethodsEight队列合并创建一个样本的1,884名参与者年龄2-36岁，其中包括1,339名子女的父母与情绪或精神病disorders，谁进行了前瞻性评估，诊断访谈平均为5.1年。为抑郁症、双相情感障碍、焦虑症、注意缺陷多动障碍（ADHD）、精神分裂症、神经质、主观幸福感、pfactor和身高（作为阴性对照）构建了PGS。考克斯回归被用来测试PGSs之间的关联，主要精神疾病的家族史，和发病的主要情绪和精神病disorders.ResultsThere是435发病的主要情绪和精神病disorders跨后续。神经质的PGS（风险比=1.23，95% CI=1.12-1.36），精神分裂症（风险比=1.15，95% CI=1.04-1.26），抑郁（风险比=1.11，95% CI=1.01-1.22），ADHD（风险比=1.10，95% CI=1.00-1.21），主观幸福感（危险比=0.90，95% CI=0.82-0.99）和p因子（危险比=1.14，95% CI=1.04-1.26）与发病相关。在控制了家族史后，神经质PGS仍然显著正相关，（风险比=1.19，95%CI =1.08-1.31）和主观幸福感PGS仍显著负相关（风险比=0.89，95%CI =0.81-0.98）。作为PGS捕获独立于家族史的主要情绪和精神病性障碍的风险，而当家族史已知时，PGS对精神疾病的预测能力有限。神经质和主观幸福感的PGS可以补充家族史的早期识别的人在高风险。
ObjectiveFamily history is an established risk factor for mental illness. The authors sought to investigate whether polygenic scores (PGSs) can complement family history to improve identification of risk for major mood and psychotic disorders.MethodsEight cohorts were combined to create a sample of 1,884 participants ages 2–36 years, including 1,339 offspring of parents with mood or psychotic disorders, who were prospectively assessed with diagnostic interviews over an average of 5.1 years. PGSs were constructed for depression, bipolar disorder, anxiety, attention deficit hyperactivity disorder (ADHD), schizophrenia, neuroticism, subjective well-being,pfactor, and height (as a negative control). Cox regression was used to test associations between PGSs, family history of major mental illness, and onsets of major mood and psychotic disorders.ResultsThere were 435 onsets of major mood and psychotic disorders across follow-up. PGSs for neuroticism (hazard ratio=1.23, 95% CI=1.12–1.36), schizophrenia (hazard ratio=1.15, 95% CI=1.04–1.26), depression (hazard ratio=1.11, 95% CI=1.01–1.22), ADHD (hazard ratio=1.10, 95% CI=1.00–1.21), subjective well-being (hazard ratio=0.90, 95% CI=0.82–0.99), andpfactor (hazard ratio=1.14, 95% CI=1.04–1.26) were associated with onsets. After controlling for family history, neuroticism PGS remained significantly positively associated (hazard ratio=1.19, 95% CI=1.08–1.31) and subjective well-being PGS remained significantly negatively associated (hazard ratio=0.89, 95% CI=0.81–0.98) with onsets.ConclusionsNeuroticism and subjective well-being PGSs capture risk of major mood and psychotic disorders that is independent of family history, whereas PGSs for psychiatric illness provide limited predictive power when family history is known. Neuroticism and subjective well-being PGSs may complement family history in the early identification of persons at elevated risk.