OBJECTIVE Identifying risk factors for major depression and depressive symptoms in youths could have important implications for prevention efforts. This study examined the association of polygenic risk scores (PRSs) for a broad depression phenotype derived from a large-scale genome-wide association study (GWAS) in adults, and its interaction with childhood abuse, with clinically relevant depression outcomes in clinical and epidemiological youth cohorts. METHODS The clinical cohort comprised 279 youths with major depression (mean age=14.76 years [SD=2.00], 68% female) and 187 healthy control subjects (mean age=14.67 years [SD=2.45], 63% female). The first epidemiological cohort included 1,450 youths (mean age=13.99 years [SD=0.92], 63% female). Of those, 694 who were not clinically depressed at baseline underwent follow-ups at 6, 12, and 24 months. The replication epidemiological cohort comprised children assessed at ages 8 (N=184; 49.2% female) and 11 (N=317; 46.7% female) years. All cohorts were genome-wide genotyped and completed measures for major depression, depressive symptoms, and/or childhood abuse. Summary statistics from the largest GWAS to date on depression were used to calculate the depression PRS. RESULTS In the clinical cohort, the depression PRS predicted case-control status (odds ratio=1.560, 95% CI=1.230-1.980), depression severity (β=0.177, SE=0.069), and age at onset (β=-0.375, SE=0.160). In the first epidemiological cohort, the depression PRS predicted baseline depressive symptoms (β=0.557, SE=0.200) and prospectively predicted onset of moderate to severe depressive symptoms (hazard ratio=1.202, 95% CI=1.045-1.383). The associations with depressive symptoms were replicated in the second epidemiological cohort. Evidence was found for an additive, but not an interactive, effect of the depression PRS and childhood abuse on depression outcomes. CONCLUSIONS Depression PRSs derived from adults generalize to depression outcomes in youths and may serve as an early indicator of clinically significant levels of depression.

中文翻译：

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多基因风险：预测青少年临床和流行病学队列中的抑郁结果。

目的识别青年人严重抑郁和抑郁症状的危险因素可能对预防工作具有重要意义。这项研究调查了成人大规模大规模全基因组关联研究（GWAS）产生的广泛抑郁表型的多基因风险评分（PRS）的关联，以及其与儿童期虐待的相互作用，以及在临床和流行病学中与临床相关的抑郁结局青年队列。方法该临床队列包括279名严重抑郁青年（平均年龄= 14.76岁[SD = 2.00]，女性68％）和187名健康对照受试者（平均年龄= 14.67岁[SD = 2.45]，女性63％）。第一个流行病学队列包括1,450名青年（平均年龄= 13.99岁[SD = 0.92]，女性占63％）。在这些患者中，有694名在基线时没有临床抑郁的患者在6、12和24个月时接受了随访。复制流行病学队列包括在8岁（N = 184； 49.2％的女性）和11岁（N = 317； 46.7％的女性）评估的儿童。所有队列均进行了全基因组基因分型，并完成了针对严重抑郁，抑郁症状和/或儿童期虐待的措施。迄今为止最大的GWAS关于抑郁症的摘要统计数据用于计算抑郁症的PRS。结果在临床队列中，抑郁症PRS预测病例控制状态（赔率= 1.560，95％CI = 1.230-1.980），抑郁症严重程度（β= 0.177，SE = 0.069）和发病年龄（β= -0.375） ，SE = 0.160）。在第一个流行病学队列中，抑郁症PRS预测基线抑郁症状（β= 0.557，SE = 0.200），并前瞻性预测中度到重度抑郁症状的发作（危险比= 1.202，95％CI = 1.045-1.383）。与抑郁症状的关联在第二个流行病学队列中重复出现。证据表明，抑郁症PRS和儿童期虐待对抑郁症结局具有累加作用，但不是交互作用。结论成人的抑郁症PRS普遍适用于年轻人的抑郁症结局，并可作为临床上重要的抑郁症水平的早期指标。