Rare DNA variants in the brain derived neurotrophic factor gene increase risk for attention deficit hyperactivity disorder : a next generation sequencing study
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Attention deficit hyperactivity disorder (ADH D) 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 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.
Hawi , Z , Cummins , T D R , Tong , J , Arcos-Burgos , M , Zhao , Q , Matthews , N , Newman , D P , Johnson , B , Vance , A , Heussler , H S , Levy , F , Easteal , S , Wray , N , Kenny , E , Morris , D , Kent , L , Gill , M & Bellgrove , M 2016 , ' Rare DNA variants in the brain derived neurotrophic factor gene increase risk for attention deficit hyperactivity disorder : a next generation sequencing study ' Molecular Psychiatry , vol Advance online . DOI: 10.1038/mp.2016.117
© 2016, Macmillan Publishers Ltd, part of Springer Nature. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at www.nature.com / https://dx.doi.org/10.1038/mp.2016.117
This work was supported by a grant from the National Health and Medical Research Council of Australia (NHMRC) (APP1065677).
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