Bright Joanna K, Rayner Christopher, Freeman Ze, Zavos Helena M S, Ahmadzadeh Yasmin I, Viding Essi, McAdams Tom A
Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.
Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.
Mol Psychiatry. 2025 Feb 19. doi: 10.1038/s41380-025-02920-6.
Prediction from polygenic scores may be confounded by sources of passive gene-environment correlation (rGE; e.g. population stratification, assortative mating, and environmentally mediated effects of parental genotype on child phenotype). Using genomic data from 10 000 twin pairs, we asked whether polygenic scores from the most recent externalising genome-wide association study predict conduct problems, ADHD symptomology and callous-unemotional traits, and whether these predictions are biased by rGE. We ran regression models including within-family and between-family polygenic scores, to separate the direct genetic influence on a trait from environmental influences that correlate with genes (indirect genetic effects). Findings suggested that this externalising polygenic score is a good index of direct genetic influence on conduct and ADHD-related symptoms across development, with minimal bias from rGE, although the polygenic score predicted less variance in CU traits. Post-hoc analyses showed some indirect genetic effects acting on a common factor indexing stability of conduct problems across time and contexts.
多基因评分的预测可能会受到被动基因-环境相关性（rGE；例如群体分层、选型交配以及父母基因型对儿童表型的环境介导效应）来源的混淆。利用来自10000对双胞胎的基因组数据，我们探究了最新的外化全基因组关联研究中的多基因评分是否能预测行为问题、注意力缺陷多动障碍（ADHD）症状以及冷酷无情特质，以及这些预测是否受到rGE的偏差影响。我们运行了回归模型，包括家庭内部和家庭之间的多基因评分，以将对某一特质的直接遗传影响与与基因相关的环境影响（间接遗传效应）区分开来。研究结果表明，这种外化多基因评分是对整个发育过程中行为和ADHD相关症状的直接遗传影响的良好指标，rGE造成的偏差最小，尽管该多基因评分预测冷酷无情特质的方差较小。事后分析显示，一些间接遗传效应作用于一个共同因素，该因素反映了行为问题在不同时间和情境下的稳定性。
