Direct and indirect genetic effects on early neurodevelopmental traits.

IF 6.5 1区 医学 Q1 PSYCHIATRY
Laura Hegemann, Espen Eilertsen, Johanne Hagen Pettersen, Elizabeth C Corfield, Rosa Cheesman, Leonard Frach, Ludvig Daae Bjørndal, Helga Ask, Beate St Pourcain, Alexandra Havdahl, Laurie J Hannigan
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引用次数: 0

Abstract

Background: Neurodevelopmental conditions are highly heritable. Recent studies have shown that genomic heritability estimates can be confounded by genetic effects mediated via the environment (indirect genetic effects). However, the relative importance of direct versus indirect genetic effects on early variability in traits related to neurodevelopmental conditions is unknown.

Methods: The sample included up to 24,692 parent-offspring trios from the Norwegian MoBa cohort. We use Trio-GCTA to estimate latent direct and indirect genetic effects on mother-reported neurodevelopmental traits at age of 3 years (restricted and repetitive behaviors and interests, inattention, hyperactivity, language, social, and motor development). Further, we investigate to what extent direct and indirect effects are attributable to common genetic variants associated with autism, ADHD, developmental dyslexia, educational attainment, and cognitive ability using polygenic scores (PGS) in regression modeling.

Results: We find evidence for contributions of direct and indirect latent common genetic effects to inattention (direct: explaining 4.8% of variance, indirect: 6.7%) hyperactivity (direct: 1.3%, indirect: 9.6%), and restricted and repetitive behaviors (direct: 0.8%, indirect: 7.3%). Direct effects best explained variation in social and communication, language, and motor development (5.1%-5.7%). Direct genetic effects on inattention were captured by PGS for ADHD, educational attainment, and cognitive ability, whereas direct genetic effects on language development were captured by cognitive ability, educational attainment, and autism PGS. Indirect genetic effects on neurodevelopmental traits were primarily captured by educational attainment and/or cognitive ability PGS.

Conclusions: Results were consistent with differential contributions to neurodevelopmental traits in early childhood from direct and indirect genetic effects. Indirect effects were particularly important for hyperactivity and restricted and repetitive behaviors and interests and may be linked to genetic variation associated with cognition and educational attainment. Our findings illustrate the importance of within-family methods for disentangling genetic processes that influence early neurodevelopmental traits, even when identifiable associations are small.

遗传对早期神经发育特征的直接和间接影响。
背景:神经发育疾病具有高度遗传性。最近的研究表明,通过环境介导的遗传效应(间接遗传效应)可能会混淆基因组遗传力的估计。然而,直接与间接遗传效应对神经发育相关性状早期变异的相对重要性尚不清楚。方法:样本包括来自挪威MoBa队列的多达24,692个父母-后代三人组。我们使用Trio-GCTA来估计3岁时母亲报告的神经发育特征(限制和重复行为和兴趣,注意力不集中,多动,语言,社交和运动发育)的潜在直接和间接遗传影响。此外,我们使用回归模型中的多基因评分(PGS)研究了与自闭症、多动症、发育性阅读障碍、教育程度和认知能力相关的常见遗传变异在多大程度上可归因于直接和间接影响。结果:我们发现了直接和间接的潜在共同遗传效应对注意力不集中(直接:解释方差的4.8%,间接:6.7%)多动(直接:1.3%,间接:9.6%)和限制和重复行为(直接:0.8%,间接:7.3%)的贡献的证据。直接影响最好地解释了社会和沟通、语言和运动发展方面的差异(5.1%-5.7%)。ADHD、受教育程度和认知能力的PGS捕获了注意力不集中的直接遗传影响,而认知能力、受教育程度和自闭症的PGS捕获了语言发展的直接遗传影响。遗传对神经发育性状的间接影响主要体现在受教育程度和/或认知能力PGS上。结论:结果与直接和间接遗传效应对儿童早期神经发育特征的差异贡献一致。间接影响对多动、受限和重复的行为和兴趣尤其重要,可能与认知和教育程度相关的遗传变异有关。我们的研究结果说明了家庭内部方法对于解开影响早期神经发育特征的遗传过程的重要性,即使可识别的关联很小。
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来源期刊
CiteScore
13.80
自引率
5.30%
发文量
169
审稿时长
1 months
期刊介绍: The Journal of Child Psychology and Psychiatry (JCPP) is a highly regarded international publication that focuses on the fields of child and adolescent psychology and psychiatry. It is recognized for publishing top-tier, clinically relevant research across various disciplines related to these areas. JCPP has a broad global readership and covers a diverse range of topics, including: Epidemiology: Studies on the prevalence and distribution of mental health issues in children and adolescents. Diagnosis: Research on the identification and classification of childhood disorders. Treatments: Psychotherapeutic and psychopharmacological interventions for child and adolescent mental health. Behavior and Cognition: Studies on the behavioral and cognitive aspects of childhood disorders. Neuroscience and Neurobiology: Research on the neural and biological underpinnings of child mental health. Genetics: Genetic factors contributing to the development of childhood disorders. JCPP serves as a platform for integrating empirical research, clinical studies, and high-quality reviews from diverse perspectives, theoretical viewpoints, and disciplines. This interdisciplinary approach is a key feature of the journal, as it fosters a comprehensive understanding of child and adolescent mental health. The Journal of Child Psychology and Psychiatry is published 12 times a year and is affiliated with the Association for Child and Adolescent Mental Health (ACAMH), which supports the journal's mission to advance knowledge and practice in the field of child and adolescent mental health.
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