Association of Genome-Wide Polygenic Scores for Multiple Psychiatric and Common Traits in Preadolescent Youths at Risk of Suicide.
Association of Genome-Wide Polygenic Scores for Multiple Psychiatric and Common Traits in Preadolescent Youths at Risk of Suicide.
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DOI：
10.1001/jamanetworkopen.2021.48585
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发表时间：
2022-02-01
影响因子：
13.8
通讯作者：
Cha J
中科院分区：
文献类型：
--
作者：
Joo YY;Moon SY;Wang HH;Kim H;Lee EJ;Kim JH;Posner J;Ahn WY;Choi I;Kim JW;Cha J
在青春期前青年中，特定精神病和常见特征的全基因组多基因评分与自杀高风险相关吗？在这项对美国11869名青春期前青年的队列研究中，多个全基因组多基因评分与自杀想法和行为（意念或企图）显著相关;与自杀风险相关的特定全基因组多基因评分包括注意力缺陷/多动障碍，总体幸福感和创伤后应激障碍。这些结果表明，基因组方法可能有助于识别自杀想法和行为的高风险儿童。自杀是全世界青年人死亡的第二大原因，但目前还没有办法确定这一人群的自杀风险。评估精神病和常见特征的全基因组多基因评分是否与青春期前儿童的自杀风险相关，并调查早期生活压力（一个主要的环境风险因素）和多基因因素之间的相互作用是否以及在多大程度上与青少年的自杀想法和行为相关。这项队列研究分析了来自青少年大脑和认知发展研究的11869名9至10岁青春期前儿童的基因型-表型数据。数据收集时间为2016年9月1日至2018年10月21日，分析时间为2020年8月1日至2021年1月3日。使用机器学习方法，估计了24个复杂性状的全基因组多基因评分，以研究它们在评估自杀想法和行为（自杀意念[主动，被动和整体]和自杀企图）风险方面的全表型关联和效用。全基因组多基因评分用于测量24个特征，包括精神障碍、认知能力、人格和心理特征。儿童行为量表用于测量早期生活压力，家庭环境量表用于评估家庭环境。自杀意念和自杀企图来自计算机化版本的儿童情感障碍和精神分裂症量表。在美国11869名青春期前儿童中，多种族队列中7140名参与者的表型结局、基因型和协变量的完整数据可用（平均[SD]年龄，9.9 [0.6]岁; 3588名女孩[50.3%]），包括925名有自杀意念的参与者和63名有自杀企图的参与者。在这7140名参与者中，729人有非洲血统（自我报告的种族或民族：569名黑人，71名西班牙裔和89名其他），276名有美国血统（自我报告人种或种族：265名西班牙裔，3名白色，8名其他），150名有东亚血统（自我报告人种或种族：67名亚洲人，18名西班牙人和65名其他人），5718名有欧洲血统（自我报告人种或种族：7名亚洲人、39名黑人、1142名西班牙人、3934名白色人和596名其他人），267名有其他祖先（自我报告人种或种族：70名亚洲人、13名黑人、126名西班牙人、48名白色人和10名其他人）。三个全基因组多基因评分显著相关（错误发现率P < .05）在所有参与者中有自杀想法和行为：注意力缺陷/多动障碍（比值比[OR]，1.12; 95% CI，1.05-1.21; P = .001），精神分裂症（OR，1.50; 95% CI，1.17-1.93; P = .002）和总体幸福感（OR，0.89; 95% CI，0.83-0.96; P = .002）。在包括只有欧洲血统的儿童的分析中，另外3个具有错误发现率显著性的全基因组多基因评分与自杀想法和行为相关：自闭症谱系障碍（OR，1.18; 95% CI，1.06-1.31; P = .002），重度抑郁障碍（OR，1.12; 95%CI，1.04-1.21; P = .003）和创伤后应激障碍（OR，1.12; 95%CI，1.04-1.21; P = .004）。发现全基因组多基因评分与环境之间存在显著的相互作用，自闭症谱系障碍的遗传风险因素和早期生活压力水平与总体自杀意念和总体自杀想法和行为的风险增加相关（OR，1.20; 95%CI，1.07-1.35; P = .002）。使用多性状全基因组多基因评分和额外的自我报告问卷数据的机器学习模型（儿童行为检查表和家庭环境量表）对总体自杀想法和行为进行了中等准确的估计（受试者工作特征曲线下面积[AUROC]，0.77; 95% CI，0.73-0.81;准确度，0.67）和自杀意念（AUROC，0.76; 95% CI，0.72-0.80;准确度，0.66）。在多种族队列的所有儿童中，综合模型在估计总体自杀想法和行为（AUROC，0.71; 95%CI，0.67-0.75;准确性，0.68）和自杀意念（AUROC，0.75; 95%CI，0.71-0.78;准确性，0.67）的风险方面也优于基线模型。在这项针对美国青春期前青少年的队列研究中，精神疾病（如注意力缺陷/多动障碍、自闭症谱系障碍、创伤后应激障碍和精神分裂症）的全基因组多基因评分较高，与自杀意念和自杀企图的风险较高显著相关。这项研究的发现和定量模型可能有助于识别自杀风险高的儿童，可能有助于早期筛查，干预和预防。这项队列研究评估了美国青春期前儿童的精神病和常见特征的全基因组多基因评分与自杀风险之间的关联。
Are genome-wide polygenic scores for specific psychiatric and common traits associated with high risk of suicide among preadolescent youths? In this cohort study of 11 869 preadolescent youths in the US, multiple genome-wide polygenic scores were significantly associated with suicidal thoughts and behaviors (ideation or attempts); specific genome-wide polygenic scores associated with the risk of suicide included attention-deficit/hyperactivity disorder, general happiness, and posttraumatic stress disorder. These results suggest that the genomic approach may be useful for identifying children at high risk for suicidal thoughts and behaviors. Suicide is the second leading cause of death among youths worldwide, but no available means exist to identify the risk of suicide in this population. To assess whether genome-wide polygenic scores for psychiatric and common traits are associated with the risk of suicide among preadolescent children and to investigate whether and to what extent the interaction between early life stress (a major environmental risk factor) and polygenic factors is associated with suicidal thoughts and behaviors among youths. This cohort study analyzed the genotype-phenotype data of 11 869 preadolescent children aged 9 to 10 years from the Adolescent Brain and Cognitive Development study. Data were collected from September 1, 2016, to October 21, 2018, and analyzed from August 1, 2020, to January 3, 2021. Using machine learning approaches, genome-wide polygenic scores of 24 complex traits were estimated to investigate their phenome-wide associations and utility for assessing risk of suicidal thoughts and behaviors (suicidal ideation [active, passive, and overall] and suicide attempt). Genome-wide polygenic scores were used to measure 24 traits, including psychiatric disorders, cognitive capacity, and personality and psychological characteristics. The Child Behavior Checklist was used to measure early life stress, and the Family Environment Scale was used to assess family environment. Suicidal ideation and suicide attempts were derived from the computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia. Among 11 869 preadolescent children in the US, complete data for phenotypic outcomes, genotypes, and covariates were available for 7140 participants in the multiethnic cohort (mean [SD] age, 9.9 [0.6] years; 3588 girls [50.3%]), including 925 participants with suicidal ideation and 63 participants with suicide attempts. Among those 7140 participants, 729 had African ancestry (self-reported race or ethnicity: 569 Black, 71 Hispanic, and 89 other), 276 had admixed American ancestry (self-reported race or ethnicity: 265 Hispanic, 3 White, and 8 other), 150 had East Asian ancestry (self-reported race or ethnicity: 67 Asian, 18 Hispanic, and 65 other), 5718 had European ancestry (self-reported race or ethnicity: 7 Asian, 39 Black, 1142 Hispanic, 3934 White, and 596 other), and 267 had other ancestries (self-reported race or ethnicity: 70 Asian, 13 Black, 126 Hispanic, 48 White, and 10 other). Three genome-wide polygenic scores were significantly associated (false discovery rate P < .05) with suicidal thoughts and behaviors among all participants: attention-deficit/hyperactivity disorder (odds ratio [OR], 1.12; 95% CI, 1.05-1.21; P = .001), schizophrenia (OR, 1.50; 95% CI, 1.17-1.93; P = .002), and general happiness (OR, 0.89; 95% CI, 0.83-0.96; P = .002). In the analysis including only children with European ancestry, 3 additional genome-wide polygenic scores with false discovery rate significance were associated with suicidal thoughts and behaviors: autism spectrum disorder (OR, 1.18; 95% CI, 1.06-1.31; P = .002), major depressive disorder (OR, 1.12; 95% CI, 1.04-1.21; P = .003), and posttraumatic stress disorder (OR, 1.12; 95% CI, 1.04-1.21; P = .004). A significant interaction between genome-wide polygenic scores and environment was found, with genetic risk factors for autism spectrum disorder and the level of early life stress associated with increases in the risk of overall suicidal ideation and overall suicidal thoughts and behaviors (OR, 1.20; 95% CI, 1.07-1.35; P = .002). A machine learning model using multitrait genome-wide polygenic scores and additional self-reported questionnaire data (Child Behavior Checklist and Family Environment Scale) produced a moderately accurate estimate of overall suicidal thoughts and behaviors (area under the receiver operating characteristic curve [AUROC], 0.77; 95% CI, 0.73-0.81; accuracy, 0.67) and suicidal ideation (AUROC, 0.76; 95% CI, 0.72-0.80; accuracy, 0.66) among children with European ancestry only. Among all children in the multiethnic cohort, the integrated model also outperformed the baseline model in estimating the risk of overall suicidal thoughts and behaviors (AUROC, 0.71; 95% CI, 0.67-0.75; accuracy, 0.68) and suicidal ideation (AUROC, 0.75; 95% CI, 0.71-0.78; accuracy, 0.67). In this cohort study of preadolescent youths in the US, higher genome-wide polygenic scores for psychiatric disorders, such as attention-deficit/hyperactivity disorder, autism spectrum disorder, posttraumatic stress disorder, and schizophrenia, were significantly associated with a greater risk of suicidal ideation and suicide attempt. The findings and quantitative models from this study may help to identify children with a high risk of suicide, potentially assisting with early screening, intervention, and prevention. This cohort study assesses the association between genome-wide polygenic scores for psychiatric and common traits and the risk of suicide among preadolescent children in the US.
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影响因子：
7.3
作者：
Anestis, Michael D.;Pennings, Stephanie M.;Gratz, Kim L.
通讯作者：
Gratz, Kim L.
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
DOI：
10.1176/appi.ajp.2020.19101025
发表时间：
2020-10-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Docherty AR;Shabalin AA;DiBlasi E;Monson E;Mullins N;Adkins DE;Bacanu SA;Bakian AV;Crowell S;Chen D;Darlington TM;Callor WB;Christensen ED;Gray D;Keeshin B;Klein M;Anderson JS;Jerominski L;Hayward C;Porteous DJ;McIntosh A;Li Q;Coon H
通讯作者：
Coon H
DOI：
10.3109/15622975.2011.597875
发表时间：
2013-12
期刊：
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
影响因子：
--
作者：
Galfalvy H;Zalsman G;Huang YY;Murphy L;Rosoklija G;Dwork AJ;Haghighi F;Arango V;Mann JJ
通讯作者：
Mann JJ
影响因子：
2.1
作者：
Conomos MP;Miller MB;Thornton TA
通讯作者：
Thornton TA