Do polygenic indices capture "direct" effects on child externalizing behavior? Within-family analyses in two longitudinal birth cohorts.
Do polygenic indices capture "direct" effects on child externalizing behavior? Within-family analyses in two longitudinal birth cohorts.
复制标题
多基因指数是否捕获了对儿童外化行为的“直接”影响？
DOI：
10.1101/2023.05.31.23290802
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Tanksley PT
中科院分区：
文献类型：
--
作者：
Tanksley PT
以自我调节困难为特征的行为和障碍，如有问题的物质使用、反社会行为和注意力缺陷/多动障碍（ADHD）症状，给个人、家庭和社区带来高昂的代价。这些外化行为通常出现在生命历程的早期，并可能产生深远的影响。长期以来，研究人员一直对外化行为的遗传风险的直接测量感兴趣，这可以与其他已知的风险因素结合起来，以提高早期识别和干预的努力。在一项预先登记的分析中，我们利用了来自英国的两个纵向队列——环境风险（E-Risk）纵向双胞胎研究（N=862对双胞胎）和千年队列研究（MCS； N= 2824对父母-孩子三胞胎）的数据，利用分子遗传数据和家庭内部设计来测试外化行为的遗传影响，这些影响不受环境干扰的常见来源的影响。结果与以下结论一致：外化多基因指数（PGI）捕获了遗传变异对儿童和青少年外化问题的因果影响，其效应大小与外化行为研究文献中观察到的其他既定风险因素的效应大小相当。此外，我们发现多基因关联在整个发育过程中有所不同（从5-10岁达到峰值），父母遗传（分类和父母特异性效应）和家庭水平的协变量对预测的影响很小，多基因预测中的性别差异是存在的，但只有通过家庭内部比较才能检测到。基于这些发现，我们认为外化行为的PGI是研究儿童破坏性行为发展的一种很有前途的手段。
Behaviors and disorders characterized by difficulties with self-regulation, such as problematic substance use, antisocial behavior, and symptoms of attention-deficit/hyperactivity disorder (ADHD), incur high costs for individuals, families, and communities. These externalizing behaviors often appear early in the life course and can have far-reaching consequences. Researchers have long been interested in direct measurements of genetic risk for externalizing behaviors, which can be incorporated alongside other known risk factors to improve efforts at early identification and intervention. In a preregistered analysis drawing on data from the Environmental Risk (E-Risk) Longitudinal Twin Study (N=862 twins) and the Millennium Cohort Study (MCS; N=2,824 parent-child trios), two longitudinal cohorts from the UK, we leveraged molecular genetic data and within-family designs to test for genetic effects on externalizing behavior that are unbiased by the common sources of environmental confounding. Results are consistent with the conclusion that an externalizing polygenic index (PGI) captures causal effects of genetic variants on externalizing problems in children and adolescents, with an effect size that is comparable to those observed for other established risk factors in the research literature on externalizing behavior. Additionally, we find that polygenic associations vary across development (peaking from age 5–10 years), that parental genetics (assortment and parent-specific effects) and family-level covariates affect prediction little, and that sex differences in polygenic prediction are present but only detectable using within-family comparisons. Based on these findings, we believe that the PGI for externalizing behavior is a promising means for studying the development of disruptive behaviors across child development.