Jangmo Andreas, Brikell Isabell, Kuja-Halkola Ralf, Feldman Inna, Lundström Sebastian, Almqvist Catarina, Bulik Cynthia M, Larsson Henrik
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden.
Department of Economics and Business Economics National Centre for Register-Based Research Aarhus University Aarhus Denmark.
JCPP Adv. 2021 Sep 8;1(3):e12030. doi: 10.1002/jcv2.12030. eCollection 2021 Oct.
Polygenic scores (PGS) for attention-deficit/hyperactivity disorder (ADHD) negatively predicts educational attainment (EA), but it remains unclear how ADHD symptoms, PGS for EA, and shared familiar factors influence the associations between PGS for ADHD and school performance.
We combined survey data on ADHD symptoms, PGS, and register-based, objective measures of compulsory school performance at age 16 for 6049 twins in the Child and Adolescent Twin Study in Sweden. Linear and instrumental variable (IV) regression models were used to estimate the association between PGS for ADHD and grade point average (GPA), overall and by natural science, humanities, and practically oriented (e.g., sports, arts, music) subject categories. The models were adjusted for parent-rated ADHD symptoms, PGS for EA, and shared familial factors (dizygotic twin comparisons) to examine how these factors influenced the associations between PGS for ADHD and school performance.
PGS for ADHD were negatively associated with school performance; = -0.12, 95% confidence interval = (-0.15, -0.09) for overall GPA with minor differences by subject category. Adjustment for ADHD symptoms attenuated these associations to a small degree compared to PGS for EA, and shared familial factors respectively. Stronger associations were observed using IV regressions compared to linear regression. However, in the IV regression analyses, most associations between PGS for ADHD and GPA in the practically oriented subject category were not significant.
Associations between PGS for ADHD and school performance are to a small degree influenced by ADHD symptoms, compared to PGS for EA and shared familial factors. These results highlight important considerations for research using PGS for ADHD to control for genetic factors, and for future clinical applications aiming to determine genetic liability towards ADHD.
注意缺陷多动障碍(ADHD)的多基因评分(PGS)对教育成就(EA)有负面预测作用,但尚不清楚ADHD症状、EA的PGS以及共同的家庭因素如何影响ADHD的PGS与学业成绩之间的关联。
我们将瑞典儿童和青少年双胞胎研究中6049对双胞胎的ADHD症状、PGS以及基于登记的16岁义务教育成绩的客观测量数据进行了合并。使用线性和工具变量(IV)回归模型来估计ADHD的PGS与平均绩点(GPA)之间的关联,总体以及按自然科学、人文科学和实践导向(如体育、艺术、音乐)学科类别进行分析。模型针对父母评定的ADHD症状、EA的PGS以及共同的家庭因素(异卵双胞胎比较)进行了调整,以研究这些因素如何影响ADHD的PGS与学业成绩之间的关联。
ADHD的PGS与学业成绩呈负相关;总体GPA的β = -0.12,95%置信区间 = (-0.15,-0.09),各学科类别之间存在细微差异。与EA的PGS和共同的家庭因素相比,对ADHD症状进行调整后,这些关联略有减弱。与线性回归相比,使用IV回归观察到更强的关联。然而,在IV回归分析中,ADHD的PGS与实践导向学科类别中的GPA之间的大多数关联并不显著。
与EA的PGS和共同的家庭因素相比,ADHD的PGS与学业成绩之间的关联在一定程度上受到ADHD症状的影响。这些结果突出了在使用ADHD的PGS控制遗传因素的研究以及未来旨在确定ADHD遗传易感性的临床应用中的重要考虑因素。