ImportanceLeveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts.ObjectiveTo examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting.Design, Setting, and ParticipantsThis genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024.ExposuresClinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder.Main Outcomes and MeasuresDiagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables.ResultsAcross the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to >89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to >89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to >89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interaction: OR, 0.83 [95% CI, 0.74-0.94]).Conclusions and RelevanceSexual trauma and mental health polygenic scores, while correlated with one another, were independent and joint risk factors for severe mental illness in a large, diverse hospital biobank population. Furthermore, associations of schizophrenia and bipolar disorder polygenic scores with respective diagnoses were greater in those without disclosures, suggesting that genetic predisposition to mental illness as measured by polygenic scores may be less impactful in the presence of this severe environmental risk factor.

中文翻译：

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性创伤、多基因评分和心理健康诊断和结果


重要性利用真实世界的临床生物样本库来调查精神疾病的遗传和环境风险因素之间的关联，可能有助于指导临床筛查工作并评估多基因评分在不同环境背景下的可移植性。目的在临床生物样本库中检查性创伤、对心理健康结果的多基因易感性与精神分裂症、双相情感障碍和重度抑郁症临床诊断之间的关联。设计、设置和参与者这项遗传关联研究是使用位于田纳西州纳什维尔范德堡大学医学中心 （VUMC） 的医院相关生物库中的 96 002 名参与者的临床和基因分型数据进行的（包括 58 262 个个体与 1000 个基因组项目 [1KG] 北欧具有高度遗传相似性的个体，来自犹他州参考人群 [1KG-EU 聚类] 和 11 047 个与 1KG 非洲血统参考人群具有高度遗传相似性的个体尼日利亚伊巴丹的约鲁巴人 [1KG-YRI 聚集]）和马萨诸塞州波士顿的麻省总医院布莱根 （MGB） （26 693 个个体，与欧洲血统的联合超级种群 [1KG-EU 聚集] 具有高度遗传相似性]）。分析的临床数据包括 1976 年至 2023 年的诊断账单代码和临床记录。数据分析于 2022 年至 2024 年进行。主要结局和措施精神分裂症、双相情感障碍和重度抑郁症的诊断，通过汇总相关诊断计费代码确定，是 logistic 回归模型中的因变量，包括性创伤披露状态、多基因评分及其交互作用作为自变量。结果在 VUMC 和 MGB 生物库中，包括 96 002 例个体（VUMC 1KG-EU 聚类：33 011 [56.7%] 女性;中位 [范围] 年龄，56.8 [10.0 至 >89] 年;MGB 1KG-EU 聚集性：14 647 [54.9%] 女性;年龄中位数 [range] 年龄，58.0 [10.0 至 >89] 年;VUMC 1KG-YRI 聚集性：6961 [63.0%] 雌性;年龄中位数 [范围] 为 44.6 [10.1 至 >89] 年）。性创伤史与跨机构的所有心理健康状况相关（VUMC 1KG-YRI 聚集队列中精神分裂症的 ORs 范围为 8.83 [95% CI，5.50-14.18] 到 VUMC 1KG-EU 聚集队列中精神分裂症的 17.65 [95% CI，12.77-24.40]）。性创伤史和多基因评分共同解释了 3.8% 至 8.8% 的心理健康表型方差。精神分裂症和双相情感障碍多基因评分与没有性创伤记录披露的个体的心理健康结果具有更大的相关性（精神分裂症相互作用：OR，0.70 [95% CI，0.56-0.88];双相情感障碍相互作用：OR，0.83 [95% CI，0.74-0.94]）。结论和相关性性创伤和心理健康多基因评分虽然彼此相关，但在大量、多样化的医院生物样本库人群中是严重精神疾病的独立和共同危险因素。 此外，在没有披露的那些人中，精神分裂症和双相情感障碍多基因评分与各自诊断的关联更大，这表明在存在这种严重的环境风险因素的情况下，通过多基因评分衡量的精神疾病的遗传易感性可能较小。