Early Manifestations of Neurodevelopmental Copy Number Variants in Children: A Population-Based Investigation

作者：Charlotte A. Dennison, Joanna Martin, Amy Shakeshaft, Lucy Riglin, Victoria E. Powell, George Kirov, Michael John Owen, Michael C. O’Donovan, Anita Thapar · 发表于：Biological Psychiatry · 年份：2025 · DOI：10.1016/j.biopsych.2025.03.004 · 被引用次数：9 · 研究领域：Genomic variations and chromosomal abnormalities、Genetics and Neurodevelopmental Disorders、Genomics and Rare Diseases

BACKGROUND: There is clinical interest in recognizing copy number variants (CNVs) in children because many have immediate and long-term health implications. Neurodevelopmental (ND) CNVs are associated with intellectual disability, autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD), conditions typically diagnosed by medical practitioners. However, ND CNVs may have additional, early developmental impacts that have yet to be examined in unselected populations. METHODS: Carriers of known ND CNVs were identified in 2 UK birth cohorts: ALSPAC (Avon Longitudinal Study of Parents and Children) (carriers = 144, controls = 6217) and MCS (Millennium Cohort Study) (carriers = 151, controls = 6559). In ALSPAC, we assessed associations between CNV carrier status and birth complications; preschool development; cognitive ability; ND conditions (ASD, ADHD, reading, language, and motor difficulties); and psychiatric, social, and educational outcomes. Corresponding phenotypes were identified in MCS and meta-analyzed, where available. RESULTS: In ALSPAC, ND CNVs were associated with low cognitive ability, ADHD, and ASD. ND CNV carriers showed a greater likelihood of preterm birth, fine and gross motor delay, difficulties in motor coordination, language, and reading, and special educational needs (SEND). Meta-analysis with available measures in MCS identified elevated likelihood of ASD, ADHD, low birth weight, reading difficulties, SEND, and peer problems. CONCLUS...