Aggression and callous, uncaring, and unemotional (CU) traits are clinically related behavioral constructs caused by genetic and environmental factors. We performed polygenic risk score (PRS) analyses to investigate shared genetic etiology between aggression and these three CU-traits. Furthermore, we studied interactions of PRS with smoking during pregnancy and childhood life events in relation to CU-traits. Summary statistics for the base phenotype were derived from the EAGLE-consortium genome-wide association study of children's aggressive behavior and were used to calculate individual-level genome-wide and gene-set PRS in the NeuroIMAGE target-sample. Target phenotypes were 'callousness', 'uncaring', and 'unemotional' sumscores of the Inventory of Callous-Unemotional traits. A total of 779 subjects and 1,192,414 single-nucleotide polymorphisms were available for PRS-analyses. Gene-sets comprised serotonergic, dopaminergic, glutamatergic, and neuroendocrine signaling pathways. Genome-wide PRS showed evidence of association with uncaring scores (explaining up to 1.59% of variance; self-contained Q = 0.0306, competitive-P = 0.0015). Dopaminergic, glutamatergic, and neuroendocrine PRS showed evidence of association with unemotional scores (explaining up to 1.33, 2.00, and 1.20% of variance respectively; self-contained Q-values 0.037, 0.0115, and 0.0473 respectively, competitive-P-values 0.0029, 0.0002, and 0.0045 respectively). Smoking during pregnancy related to callousness scores while childhood life events related to both callousness and unemotionality. Moreover, dopaminergic PRS appeared to interact with childhood life events in relation to unemotional scores. Our study provides evidence suggesting shared genetic etiology between aggressive behavior and uncaring, and unemotional CU-traits in children. Gene-set PRS confirmed involvement of shared glutamatergic, dopaminergic, and neuroendocrine genetic variation in aggression and CU-traits. Replication of current findings is needed.

中文翻译：

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基于侵略性的全基因组，谷氨酸能，多巴胺能和神经内分泌多基因风险评分可预测call性情绪低落特征。

侵略性和残酷，漠不关心和不情绪化（CU）特质是由遗传和环境因素引起的临床相关行为建构。我们进行了多基因风险评分（PRS）分析，以研究侵略性与这三个CU特性之间的共同遗传病因。此外，我们研究了在怀孕和儿童期生活事件中，与CU特征相关的PRS与吸烟的相互作用。基本表型的摘要统计数据来自EAGLE协会对儿童攻击行为的全基因组关联研究，并用于计算NeuroIMAGE目标样本中的个人水平全基因组和基因组PRS。目标表型是“无情-非情感性状”量表的“无情”，“漠不关心”和“无情”总结。共有779个科目和1,192个，414个单核苷酸多态性可用于PRS分析。基因集包括血清素能，多巴胺能，谷氨酸能和神经内分泌信号通路。全基因组的PRS显示出与无心得分相关的证据（解释方差高达1.59％；独立的Q = 0.0306，竞争性P = 0.0015）。多巴胺能，谷氨酸能和神经内分泌PRS显示出与非情绪评分相关的证据（分别解释高达1.33％，2.00％和1.20％的方差；独立的Q值分别为0.037、0.0115和0.0473，竞争性P值为0.0029，分别为0.0002和0.0045）。怀孕期间吸烟与伤风感分数相关，而儿童时期的生活事件与伤风感和情绪低落相关。此外，多巴胺能性PRS似乎与儿童生活事件有关的情绪低落分数相互作用。我们的研究提供了证据，表明儿童的攻击行为与无理，无情感的CU特征之间存在共同的遗传病因。基因组PRS证实了侵略性和CU性状涉及共同的谷氨酸能，多巴胺能和神经内分泌遗传变异。需要复制当前的发现。