The field of genomics is the principal avenue in the ongoing development of precision/personalised medicine for a variety of health conditions. However, relating genes to outcomes is notoriously complex, especially when considering that other variables can change, or moderate, gene-outcome associations. Here, we comprehensively discuss moderation of gene-outcome associations in the context of traumatic brain injury (TBI), a common, chronically debilitating, and costly neurological condition that is under complex polygenic influence. We focus our narrative review on single nucleotide polymorphisms (SNPs) of three of the most studied genes (apolipoprotein E, brain-derived neurotrophic factor, and catechol-O-methyltransferase) and on three demographic variables believed to moderate associations between these SNPs and TBI outcomes (age, biological sex, and ethnicity). We speculate on the mechanisms which may underlie these moderating effects, drawing widely from biomolecular and behavioural research (n = 175 scientific reports) within the TBI population (n = 72) and other neurological, healthy, ageing, and psychiatric populations (n = 103). We conclude with methodological recommendations for improved exploration of moderators in future genetics research in TBI and other populations.

基因组学领域是针对各种健康状况持续开发精准/个性化医学的主要途径。然而，众所周知，将基因与结果相关联是非常复杂的，尤其是在考虑到其他变量可能会改变或缓和基因与结果的关联时。在这里，我们全面讨论了外伤性脑损伤 (TBI) 背景下基因-结果关联的调节，这是一种常见的、慢性衰弱且代价高昂的神经系统疾病，受复杂的多基因影响。我们将叙述性回顾集中在三个研究最多的基因（载脂蛋白 E、脑源性神经营养因子和儿茶酚-O-甲基转移酶）的单核苷酸多态性 (SNP) 上）和三个人口统计学变量，这些变量被认为可以调节这些 SNP 和 TBI 结果（年龄、生理性别和种族）之间的关联。我们从TBI 人群 ( n = 72) 和其他神经系统、健康、老龄化和精神病人群 ( n = 103 ) 中的生物分子和行为研究 ( n = 175 科学报告) 中推测可能构成这些调节作用的机制。）。最后，我们提出了方法学建议，以在 TBI 和其他人群的未来遗传学研究中改进对调节剂的探索。