BACKGROUND Low replication rates are a concern in most, if not all, scientific disciplines. In psychiatric genetics specifically, targeting intermediate brain phenotypes, which are more closely associated with putative genetic effects, was touted as a strategy leading to increased power and replicability. In the current study, we attempted to replicate previously published associations between single nucleotide polymorphisms and threat-related amygdala reactivity, which represents a robust brain phenotype not only implicated in the pathophysiology of multiple disorders, but also used as a biomarker of future risk. METHODS We conducted a literature search for published associations between single nucleotide polymorphisms and threat-related amygdala reactivity and found 37 unique findings. Our replication sample consisted of 1117 young adult volunteers (629 women, mean age 19.72 ± 1.25 years) for whom both genetic and functional magnetic resonance imaging data were available. RESULTS Of the 37 unique associations identified, only three replicated as previously reported. When exploratory analyses were conducted with different model parameters compared to the original findings, significant associations were identified for 28 additional studies: eight of these were for a different contrast/laterality; five for a different gender and/or race/ethnicity; and 15 in the opposite direction and for a different contrast, laterality, gender, and/or race/ethnicity. No significant associations, regardless of model parameters, were detected for six studies. Notably, none of the significant associations survived correction for multiple comparisons. CONCLUSIONS We discuss these patterns of poor replication with regard to the general strategy of targeting intermediate brain phenotypes in genetic association studies and the growing importance of advancing the replicability of imaging genetics findings.

中文翻译：

---

成像遗传学的可重复性：与威胁相关的杏仁核反应性案例

背景低复制率在大多数（如果不是全部）科学学科中是一个问题。特别是在精神病遗传学中，针对与推定的遗传效应更密切相关的中间脑表型被吹捧为一种导致增加力量和可复制性的策略。在目前的研究中，我们试图复制先前发表的单核苷酸多态性与威胁相关杏仁核反应性之间的关联，这代表了一种强大的大脑表型，不仅涉及多种疾病的病理生理学，而且还用作未来风险的生物标志物。方法我们对已发表的单核苷酸多态性与威胁相关杏仁核反应性之间的关联进行了文献检索，并发现了 37 项独特的发现。我们的复制样本由 1117 名年轻的成年志愿者（629 名女性，平均年龄 19.72 ± 1.25 岁）组成，他们的遗传和功能磁共振成像数据都是可用的。结果 在确定的 37 个独特关联中，只有 3 个重复，如先前报道的那样。当使用与原始发现相比不同的模型参数进行探索性分析时，发现了 28 项额外研究的显着关联：其中 8 项是针对不同的对比/偏侧性；五个不同的性别和/或种族/民族；和 15 在相反的方向和不同的对比、偏向性、性别和/或种族/民族。无论模型参数如何，六项研究均未检测到显着关联。值得注意的是，没有一个重要的关联在多重比较的校正中幸存下来。