Risk of Psychiatric Disorders Among Individuals With the 22q11.2 Deletion or Duplication A Danish Nationwide, Register-Based Study
Risk of Psychiatric Disorders Among Individuals With the 22q11.2 Deletion or Duplication A Danish Nationwide, Register-Based Study
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DOI：
10.1001/jamapsychiatry.2016.3939
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发表时间：
2017-03-01
期刊：
影响因子：
25.8
通讯作者：
Werge, Thomas
中科院分区：
文献类型：
--
作者：
Hoeffding, Louise K.;Trabjerg, Betina B.;Werge, Thomas
在22q11.2位点已经描述了微缺失和重复。然而，很少有人知道的临床和流行病学后果在population. ObjectiveTo水平确定指标的缺失或重复在22q11.2基因座和估计发病率比（IRR）和绝对风险的精神疾病在临床确定的个人与22q11.2缺失或重复。和参与者进行了一项丹麦全国登记研究，包括丹麦细胞遗传学中心登记处记录的所有22q11.2缺失或重复的个体。在研究期间，共对1955年至2012年出生于丹麦的3 768 943人进行了随访（总随访，5710万人年）。使用巢式病例对照设计（包括来自基于人群队列的个体）估计22q11.2缺失或重复和累积发生率指标。生存分析用于比较有和没有22q11.2缺失或重复的个体的疾病风险。本研究于2015年5月7日至2016年8月14日进行。暴露22 q11. 2缺失或重复。主要结局和指标携带22 q11. 2缺失或重复的指标、IRR和精神病诊断的累积发生率（《疾病和相关健康问题国际统计分类》，第10次修订，代码F00-F99），包括精神分裂症谱系障碍、情绪障碍、结果在3768943名参与者中，244名（124名[50.8%]男性）和58名（29名[50.0%]男性）个体分别被临床鉴定为22q11.2缺失或重复。诊断任何精神疾病的平均（SD）年龄为12.5（8.3）岁的个体与删除和6.1（0.9）岁的重复运营商。父母诊断为精神分裂症，而不是其他精神病诊断与22q11.2缺失相关，父母的精神病诊断与重复携带者状态相关。22q11.2缺失（IRR，4.24; 95%CI，3.07-5.67）和重复（IRR，4.99; 95%CI，1.79-10.72）均与任何精神疾病的风险增加相关。此外，发现缺失（IRR，34.08; 95% CI，22.39-49.27）和重复（IRR，33.86; 95% CI，8.42-87.87）的智力残疾风险高度增加。此外，22q11.2缺失的个体患几种正在研究的精神疾病的风险增加，例如，广泛性发育障碍（IRR，9.45; 95% CI，5.64-14.69）和儿童自闭症（IRR，8.94; 95%CI，3.21-19.23）.结论和相关性具有22q11.2缺失或重复的个体具有显著增加的发展为精神障碍的风险。携带22q11.2缺失或重复的人的生存分析提供了直接临床相关性的估计，有助于临床确定，遗传咨询，症状监测指导和早期临床干预。
IMPORTANCE Microdeletions and duplications have been described at the 22q11.2 locus. However, little is known about the clinical and epidemiologic consequences at the population level.OBJECTIVE To identify indicators of deletions or duplications at the 22q11.2 locus and estimate the incidence rate ratios (IRRs) and absolute risk for psychiatric disorders in clinically identified individuals with 22q11.2 deletion or duplication.DESIGN, SETTING, AND PARTICIPANTS A Danish nationwide register study including all individuals recorded in the Danish Cytogenetic Central Register with a 22q11.2 deletion or duplication was performed. A total of 3 768 943 individuals born in Denmark from 1955 to 2012 were followed up during the study period (total follow-up, 57.1 million person-years). Indicators of 22q11.2 deletion or duplication and cumulative incidences were estimated using a nested case-control design that included individuals from the population-based cohort. Survival analysis was used to compare risk of disease in individuals with and without the 22q11.2 deletion or duplication. The study was conducted from May 7, 2015, to August 14, 2016.EXPOSURE The 22q11.2 deletion or duplication.MAIN OUTCOMES AND MEASURES Indicators for carrying a 22q11.2 deletion or duplication, IRR, and cumulative incidences for psychiatric diagnoses (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, codes F00-F99), including schizophrenia-spectrum disorders, mood disorders, neurotic stress-related and somatoform disorders, and a range of developmental and childhood disorders.RESULTS Among the 3 768 943 participants, 244 (124 [50.8%] male) and 58 (29 [50.0%] male) individuals were clinically identified with a 22q11.2 deletion or duplication, respectively. Mean (SD) age at diagnosis of any psychiatric disorder was 12.5 (8.3) years for individuals with deletions and 6.1 (0.9) years for duplication carriers. A parental diagnosis of schizophrenia-but not of other psychiatric diagnoses-was associated with a 22q11.2 deletion, and parental psychiatric diagnoses other than schizophrenia were associated with duplication carrier status. Both the 22q11.2 deletion (IRR, 4.24; 95% CI, 3.07-5.67) and duplication (IRR, 4.99; 95% CI, 1.79-10.72) was associated with increased risk of any psychiatric disorders. Furthermore, a highly increased risk of intellectual disability was found for the deletion (IRR, 34.08; 95% CI, 22.39-49.27) and duplication (IRR, 33.86; 95% CI, 8.42-87.87). Furthermore, individuals with the 22q11.2 deletion had an increased risk of several psychiatric disorders under study, for example, pervasive developmental disorders (IRR, 9.45; 95% CI, 5.64-14.69) and childhood autism (IRR, 8.94; 95% CI, 3.21-19.23).CONCLUSIONS AND RELEVANCE Individuals with the 22q11.2 deletion or duplication have a significantly increased risk of developing psychiatric disorders. Survival analysis of persons carrying either the 22q11.2 deletion or duplication provides estimates of direct clinical relevance useful to assist clinical ascertainment, genetic counseling, guidance of symptomatic monitoring, and early clinical intervention.