Risk of Early-Onset Depression Associated With Polygenic Liability, Parental Psychiatric History, and Socioeconomic Status
Risk of Early-Onset Depression Associated With Polygenic Liability, Parental Psychiatric History, and Socioeconomic Status
复制标题
DOI：
10.1001/jamapsychiatry.2020.4172
复制
发表时间：
2021-01-13
期刊：
影响因子：
25.8
通讯作者：
Musliner, Katherine L.
中科院分区：
文献类型：
--
作者：
Agerbo, Esben;Trabjerg, Betina B.;Musliner, Katherine L.
重要性将多基因风险评分（PRS）与其他已知的风险因素结合起来，可能会提高对一般人群抑郁症风险的识别。然而，据我们所知，没有研究估计了PRS与抑郁症的绝对风险的关联，并且很少有研究检查了PRS和其他重要风险因素的组合，包括父母精神疾病史和社会经济地位（SES），在识别抑郁症风险中。设计、设置和参与者该病例队列研究包括来自iPSYCH 2012样本的参与者，iPSYCH 2012样本是1981年5月1日至2005年12月31日期间出生于丹麦的所有单身儿的病例队列样本。采用考克斯比例风险回归分析方法对抑郁症的危险比（HR）和绝对危险度进行了估计。以及父母有精神疾病史（重性抑郁症、双相情感障碍、其他情绪或精神障碍，和其他精神病学诊断）。主要结果和测量方法来自住院病人，门诊病人，结果从基础人群中随机抽取抑郁症患者17098例（女性11748例，占68.7%），男性18582例（9429例，占50.7%）。PRS、父母病史和较低的SES均与抑郁风险增加显著相关，PRS每增加1-SD的HR为1.32（95%CI，1.29-1.35），母亲有情绪或精神障碍病史的HR为2.23（95%CI，1.81-2.64）。完全调整的模型具有相似的效应大小，表明这些风险因素不会相互混淆。30岁时患抑郁症的绝对风险差异很大，这取决于个体的风险因素组合，范围从1.0%到1.0%。（95% CI，0.1%-2.0%）在PRS分布的底部2%中具有高SES的男性中，（95%可信区间，16.6%-30.2%）结论和相关性这项研究表明，目前抑郁症的PRS与重性抑郁症的相关性并不比其他已知的风险更大因素;然而，它们可能有助于结合其他风险因素确定风险。
IMPORTANCE Combining information on polygenic risk scores (PRSs) with other known risk factors could potentially improve the identification of risk of depression in the general population. However, to our knowledge, no study has estimated the association of PRS with the absolute risk of depression, and few have examined combinations of the PRS and other important risk factors, including parental history of psychiatric disorders and socioeconomic status (SES), in the identification of depression risk.OBJECTIVE To assess the individual and joint associations of PRS, parental history, and SES with relative and absolute risk of early-onset depression.DESIGN, SETTING, AND PARTICIPANTS This case-cohort study included participants from the iPSYCH2012 sample, a case-cohort sample of all singletons born in Denmark between May 1, 1981, and December 31, 2005. Hazard ratios (HRs) and absolute risks were estimated using Cox proportional hazards regression for case-cohort designs.EXPOSURES The PRS for depression; SES measured using maternal educational level, maternal marital status, and paternal employment; and parental history of psychiatric disorders (major depression, bipolar disorder, other mood or psychotic disorders, and other psychiatric diagnoses).MAIN OUTCOMES AND MEASURES Hospital-based diagnosis of depression from inpatient, outpatient, or emergency settings.RESULTS Participants included 17 098 patients with depression (11 748 [68.7%] female) and 18 582 (9429 [50.7%] male) individuals randomly selected from the base population. The PRS, parental history, and lower SES were all significantly associated with increased risk of depression, with HRs ranging from 1.32 (95% CI, 1.29-1.35) per 1-SD increase in PRS to 2.23 (95% CI, 1.81-2.64) for maternal history of mood or psychotic disorders. Fully adjusted models had similar effect sizes, suggesting that these risk factors do not confound one another. Absolute risk of depression by the age of 30 years differed substantially, depending on an individual's combination of risk factors, ranging from 1.0% (95% CI, 0.1%-2.0%) among men with high SES in the bottom 2% of the PRS distribution to 23.7% (95% CI, 16.6%-30.2%) among women in the top 2% of PRS distribution with a parental history of psychiatric disorders.CONCLUSIONS AND RELEVANCE This study suggests that current PRSs for depression are not more likely to be associated with major depressive disorder than are other known risk factors; however, they may be useful for the identification of risk in conjunction with other risk factors.