Choi Maia, Poore Holly E, Brislin Sarah J, Barr Peter B, Aliev Fazil, Zellers Stephanie, Saunders Gretchen R B, Salvatore Jessica E, Vrieze Scott I, Harden K Paige, Palmer Abraham A, Raevuori Anu, Latvala Antti, Dick Danielle M
Rutgers University, Piscataway, New Jersey.
Rutgers University, Piscataway, New Jersey.
J Am Acad Child Adolesc Psychiatry. 2025 Apr 23. doi: 10.1016/j.jaac.2025.04.010.
Understanding how genetic risk unfolds across development will be important for using genetics to inform prevention and early intervention. The current study leverages information from 5 large datasets to characterize behavioral manifestations of a genetic liability toward externalizing from ages 6 months to 26 years.
We used polygenic scores (PGS) derived from a multivariate genome-wide association study (GWAS) of externalizing that identified hundreds of significantly associated genetic variants (EXT) to estimate associations of genetic liability with relevant phenotypes within and across developmental periods, ranging from toddlerhood to early adulthood. We used data from 5 population- and family-based datasets spanning 3 countries.
The EXT was significantly associated with a breadth of externalizing phenotypes from toddlerhood to early adulthood. Higher EXT was consistently associated with measures of impulsivity from early adolescence to early adulthood. Individuals with higher EXT were more likely to experience conduct problems and symptoms of oppositional defiant and attention-deficit/hyperactivity disorders. Furthermore, the EXT was associated with higher levels of substance use and problems beginning in early adolescence through early adulthood, including alcohol and illicit drug use. There was minimal evidence for sex interactions.
A genetic liability toward externalizing is associated a wide array of behaviors and psychiatric/substance use outcomes beginning as early as childhood and through emerging adulthood. The early emergence and breadth of behaviors associated with a genetic liability toward externalizing could inform prevention and intervention.
了解遗传风险在整个发育过程中的表现，对于利用遗传学知识指导预防和早期干预至关重要。当前的研究利用来自5个大型数据集的信息，来描述从6个月到26岁外化行为遗传易感性的行为表现。
我们使用了从一项关于外化行为的多变量全基因组关联研究（GWAS）中得出的多基因分数（PGS），该研究识别出数百个显著相关的遗传变异（EXT），以估计遗传易感性与从幼儿期到成年早期不同发育阶段内及跨阶段的相关表型之间的关联。我们使用了来自3个国家的5个基于人群和家庭的数据集的数据。
EXT与从幼儿期到成年早期的一系列外化表型显著相关。从青春期早期到成年早期，较高的EXT一直与冲动性测量指标相关。EXT较高的个体更有可能出现行为问题以及对立违抗和注意力缺陷/多动障碍的症状。此外，从青春期早期到成年早期，EXT与更高水平的物质使用及问题相关，包括酒精和非法药物使用。几乎没有证据表明存在性别交互作用。
外化行为的遗传易感性与一系列行为以及精神/物质使用结果相关，这些行为最早从童年期开始并贯穿成年早期。与外化行为遗传易感性相关的行为的早期出现和广泛性可为预防和干预提供依据。
