PMID- 27457811
OWN - NLM
STAT- MEDLINE
DCOM- 20171010
LR  - 20181113
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Linking)
VI  - 22
IP  - 4
DP  - 2017 Apr
TI  - Rare DNA variants in the brain-derived neurotrophic factor gene increase risk for 
      attention-deficit hyperactivity disorder: a next-generation sequencing study.
PG  - 580-584
LID - 10.1038/mp.2016.117 [doi]
AB  - 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.
FAU - Hawi, Z
AU  - Hawi Z
AD  - School of Psychological Sciences and Monash Institute for Cognitive and Clinical 
      Neurosciences (MICCN), Monash University, Melbourne, VIC, Australia.
FAU - Cummins, T D R
AU  - Cummins TD
AD  - School of Psychological Sciences and Monash Institute for Cognitive and Clinical 
      Neurosciences (MICCN), Monash University, Melbourne, VIC, Australia.
FAU - Tong, J
AU  - Tong J
AUID- ORCID: 0000-0002-3269-1438
AD  - School of Psychological Sciences and Monash Institute for Cognitive and Clinical 
      Neurosciences (MICCN), Monash University, Melbourne, VIC, Australia.
FAU - Arcos-Burgos, M
AU  - Arcos-Burgos M
AD  - John Curtin School of Medical Research, Australian National University, Canberra, 
      ACT, Australia.
FAU - Zhao, Q
AU  - Zhao Q
AUID- ORCID: 0000-0002-6341-0416
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 
      Australia.
FAU - Matthews, N
AU  - Matthews N
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 
      Australia.
FAU - Newman, D P
AU  - Newman DP
AD  - School of Psychological Sciences and Monash Institute for Cognitive and Clinical 
      Neurosciences (MICCN), Monash University, Melbourne, VIC, Australia.
FAU - Johnson, B
AU  - Johnson B
AD  - School of Psychological Sciences and Monash Institute for Cognitive and Clinical 
      Neurosciences (MICCN), Monash University, Melbourne, VIC, Australia.
FAU - Vance, A
AU  - Vance A
AD  - Academic Child Psychiatry Unit, Department of Paediatrics, University of 
      Melbourne, Royal Children's Hospital, Melbourne, VIC, Australia.
FAU - Heussler, H S
AU  - Heussler HS
AD  - Mater Research Institute, University of Queensland, Brisbane, QLD, Australia.
FAU - Levy, F
AU  - Levy F
AD  - School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
AD  - Child and Family East, Prince of Wales Hospital, Randwick, NSW, Australia.
FAU - Easteal, S
AU  - Easteal S
AD  - John Curtin School of Medical Research, Australian National University, Canberra, 
      ACT, Australia.
FAU - Wray, N R
AU  - Wray NR
AUID- ORCID: 0000-0001-7421-3357
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 
      Australia.
FAU - Kenny, E
AU  - Kenny E
AD  - Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute 
      of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
FAU - Morris, D
AU  - Morris D
AUID- ORCID: 0000-0002-3413-570X
AD  - Department of Biochemistry, National University of Ireland Galway, Galway, 
      Ireland.
FAU - Kent, L
AU  - Kent L
AD  - School of Medicine, University of St Andrews, St Andrews, Scotland, UK.
FAU - Gill, M
AU  - Gill M
AUID- ORCID: 0000-0003-0206-5337
AD  - Neuropsychiatric Genetics Research Group, Department of Psychiatry and Institute 
      of Molecular Medicine, Trinity College Dublin, Dublin, Ireland.
FAU - Bellgrove, M A
AU  - Bellgrove MA
AD  - School of Psychological Sciences and Monash Institute for Cognitive and Clinical 
      Neurosciences (MICCN), Monash University, Melbourne, VIC, Australia.
AD  - Queensland Brain Institute, The University of Queensland, Brisbane, QLD, 
      Australia.
LA  - eng
PT  - Journal Article
DEP - 20160726
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adolescent
MH  - Attention Deficit Disorder with Hyperactivity/*genetics
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Case-Control Studies
MH  - Child
MH  - DNA
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genetic Variation/genetics
MH  - Genome-Wide Association Study
MH  - Genotype
MH  - High-Throughput Nucleotide Sequencing/methods
MH  - Humans
MH  - Ireland
MH  - Male
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Risk Factors
MH  - Sequence Analysis, DNA/methods
EDAT- 2016/07/28 06:00
MHDA- 2017/10/11 06:00
CRDT- 2016/07/27 06:00
PHST- 2015/10/27 00:00 [received]
PHST- 2016/04/14 00:00 [revised]
PHST- 2016/05/06 00:00 [accepted]
PHST- 2016/07/28 06:00 [pubmed]
PHST- 2017/10/11 06:00 [medline]
PHST- 2016/07/27 06:00 [entrez]
AID - mp2016117 [pii]
AID - 10.1038/mp.2016.117 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2017 Apr;22(4):580-584. doi: 10.1038/mp.2016.117. Epub 2016 Jul 
      26.