Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for attention-deficit hyperactivity disorder: A next-generation sequencing study

Z. Hawi, T. D.R. Cummins, J. Tong, M. Arcos-Burgos, Q. Zhao, N. Matthews, D. P. Newman, B. Johnson, A. Vance, H. S. Heussler, F. Levy, S. Easteal, N. R. Wray, E. Kenny, D. Morris, L. Kent, M. Gill, M. A. Bellgrove*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    27 Citations (Scopus)

    Abstract

    Attention-deficit hyperactivity disorder (ADHD) is a prevalent and highly heritable disorder of childhood with negative lifetime outcomes. Although candidate gene and genome-wide association studies have identified promising common variant signals, these explain only a fraction of the heritability of ADHD. The observation that rare structural variants confer substantial risk to psychiatric disorders suggests that rare variants might explain a portion of the missing heritability for ADHD. Here we believe we performed the first large-scale next-generation targeted sequencing study of ADHD in 152 child and adolescent cases and 188 controls across an a priori set of 117 genes. A multi-marker gene-level analysis of rare (<1% frequency) single-nucleotide variants (SNVs) revealed that the gene encoding brain-derived neurotrophic factor (BDNF) was associated with ADHD at Bonferroni corrected levels. Sanger sequencing confirmed the existence of all novel rare BDNF variants. Our results implicate BDNF as a genetic risk factor for ADHD, potentially by virtue of its critical role in neurodevelopment and synaptic plasticity.

    Original languageEnglish
    Pages (from-to)580-584
    Number of pages5
    JournalMolecular Psychiatry
    Volume22
    Issue number4
    DOIs
    Publication statusPublished - 1 Apr 2017

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