ImportanceSuicide is the third-leading cause of death among US adolescents. Environmental and lifestyle factors influence suicidal behavior and can inform risk classification, yet quantifying and incorporating them in risk assessment presents a significant challenge for reproducibility and clinical translation.ObjectiveTo quantify the aggregate contribution of environmental and lifestyle factors to youth suicide attempt risk classification.Design, Setting, and ParticipantsThis was a cohort study in 3 youth samples: 2 national longitudinal cohorts from the US and the UK and 1 clinical cohort from a tertiary pediatric US hospital. An exposome-wide association study (ExWAS) approach was used to identify risk and protective factors and compute aggregate exposomic scores. Logistic regression models were applied to test associations and model fit of exposomic scores with suicide attempts in independent data. Youth from the Adolescent Brain Cognitive Development (ABCD) study, the UK Millennium Cohort Study (MCS), and the Children’s Hospital of Philadelphia emergency department (CHOP-ED) were included in the study.ExposuresA single-weighted exposomic score that sums significant risk and protective environmental/lifestyle factors.Main Outcome and MeasureSelf-reported suicide attempt.ResultsA total of 40 364 youth were included in this analysis: 11 564 from the ABCD study (3 waves of assessment; mean [SD] age, 12.0 [0.7] years; 6034 male [52.2%]; 344 attempted suicide [3.0%]; 1154 environmental/lifestyle factors were included in the ABCD study), 9000 from the MCS cohort (mean [SD] age, 17.2 [0.3] years; 4593 female [51.0%]; 661 attempted suicide [7.3%]; 2864 environmental/lifestyle factors were included in the MCS cohort), and 19 800 from the CHOP-ED cohort (mean [SD] age, 15.3 [1.5] years; 12 937 female [65.3%]; 2051 attempted suicide [10.4%]; 36 environmental/lifestyle factors were included in the CHOP-ED cohort). In the ABCD discovery subsample, ExWAS identified 99 risk and protective exposures significantly associated with suicide attempt. A single weighted exposomic score that sums significant risk and protective exposures was associated with suicide attempt in an independent ABCD testing subsample (odds ratio [OR], 2.2; 95% CI, 2.0-2.6; P < .001) and explained 17.6% of the variance (based on regression pseudo-R2) in suicide attempt over and above that explained by age, sex, race, and ethnicity (2.8%) and by family history of suicide (6.3%). Findings were consistent in the MCS and CHOP-ED cohorts (explaining 22.6% and 19.3% of the variance in suicide attempt, respectively) despite clinical, demographic, and exposure differences. In all cohorts, compared with youth at the median quintile of the exposomic score, youth at the top fifth quintile were substantially more likely to have made a suicide attempt (OR, 4.3; 95% CI, 2.6-7.2 in the ABCD study; OR, 3.8; 95% CI, 2.7-5.3 in the MCS cohort; OR, 5.8; 95% CI, 4.7-7.1 in the CHOP-ED cohort).Conclusions and RelevanceResults suggest that exposomic scores of suicide attempt provided a generalizable method for risk classification that can be applied in diverse samples from clinical or population settings.

中文翻译：

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在 3 个大型青年队列中使用环境和生活方式因素对自杀未遂风险进行分类


重要性自杀是美国青少年的第三大死因。环境和生活方式因素会影响自杀行为，可以为风险分类提供信息，但量化和纳入风险评估对可重复性和临床转化提出了重大挑战。目的量化环境和生活方式因素对青少年自杀未遂风险分类的总体贡献。设计、设置和参与者这是一项针对 3 个青年样本的队列研究：来自美国和英国的 2 个国家纵向队列和 1 个来自美国三级儿科医院的临床队列。使用全暴露组关联研究 （ExWAS） 方法确定风险和保护因素并计算总暴露组评分。将 Logistic 回归模型应用于检验暴露组评分与独立数据中自杀未遂的关联和模型拟合。来自青少年脑认知发展 （ABCD） 研究、英国千年队列研究 （MCS） 和费城儿童医院急诊科 （CHOP-ED） 的青少年被纳入该研究。暴露（Exposures）一种单加权暴露综合征评分，用于汇总重大风险和保护性环境/生活方式因素。主要结局和测量自我报告的自杀未遂。结果本分析共纳入 40 364 名青少年： 11 564 名来自 ABCD 研究（3 波评估;平均 [SD] 年龄，12.0 [0.7] 岁;6034 名男性 [52.2%];344 名自杀未遂 [3.0%];1154 个环境/生活方式因素被纳入 ABCD 研究），9000 名来自 MCS 队列（平均 [SD] 年龄，17.2 [0.3] 岁;4593 名女性 [51.0%];661 名自杀未遂 [7.3%];2864 个环境/生活方式因素包含在 MCS 队列中）， 和 19 800 名来自 CHOP-ED 队列（平均 [SD] 年龄，15.3 [1.5] 年;12 937 名女性 [65.3%];2051 人自杀未遂 [10.4%];CHOP-ED 队列包括 36 个环境/生活方式因素）。在 ABCD 发现子样本中，ExWAS 确定了 99 例与自杀未遂显著相关的风险和保护性暴露。在独立的 ABCD 测试子样本中，将重大风险和保护性暴露相加的单一加权暴露组评分与自杀未遂相关（比值比 [OR]，2.2;95% CI，2.0-2.6;P < .001），并解释了自杀未遂中 17.6% 的方差（基于回归伪 R2），超过了由年龄、性别、种族和民族 （2.8%） 和自杀家族史 （6.3%） 解释的方差。尽管临床、人口统计学和暴露存在差异，但在 MCS 和 CHOP-ED 队列中，研究结果是一致的（分别解释了自杀未遂方差的 22.6% 和 19.3%）。在所有队列中，与暴露组评分中位数五分之一的青少年相比，前五分之一的青少年自杀未遂的可能性要高得多（OR，4.3;95% CI，ABCD 研究中为 2.6-7.2;OR，3.8;95% CI，MCS 队列中为 2.7-5.3;或者，5.8;95% CI，CHOP-ED 队列中为 4.7-7.1）。结论和相关性结果表明，自杀未遂的暴露组评分提供了一种可推广的风险分类方法，可应用于来自临床或人群环境的不同样本。