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A case-control genome-wide association study of ADHD discovers a novel association with the tenascin R (TNR) gene

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Hawi_2018_A_case_controlled_TP_284_CC.pdf (1.013Mb)
Date
18/12/2018
Author
Hawi, Ziarih
Yates, Hannah
Pinar, Ari
Johnson, Beth
Tong, Janette
Pugsley, Kealan
Dark, Callum
Pauper, Mark
Klein, Marieke
Heussler, Helen S
Hiscock, Harriet
Fornito, Alex
Tiego, Jeggan
Finlay, Amy
Vance, Alasdair
Gill, Michael
Kent, Lindsey Sian
Bellgrove, Mark A.
Keywords
QH426 Genetics
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
NDAS
BDC
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Abstract
It is well-established that there is a strong genetic contribution to the aetiology of attention deficit hyperactivity disorder (ADHD). Here, we employed a hypothesis-free genome-wide association study (GWAS) design in a sample of 480 clinical childhood ADHD cases and 1208 controls to search for novel genetic risk loci for ADHD. DNA was genotyped using Illumina’s Human Infinium PsychArray-24v1.2., and the data were subsequently imputed to the 1000 Genomes reference panel. Rigorous quality control and pruning of genotypes at both individual subject and single nucleotide polymorphism (SNP) levels was performed. Polygenic risk score (PGRS) analysis revealed that ADHD case–control status was explained by genetic risk for ADHD, but no other major psychiatric disorders. Logistic regression analysis was performed genome-wide to test the association between SNPs and ADHD case–control status. We observed a genome-wide significant association (p = 3.15E−08) between ADHD and rs6686722, mapped to the Tenascin R (TNR) gene. Members of this gene family are extracellular matrix glycoproteins that play a role in neural cell adhesion and neurite outgrowth. Suggestive evidence of associations with ADHD was observed for an additional 111 SNPs (⩽9.91E−05). Although intriguing, the association between DNA variation in the TNR gene and ADHD should be viewed as preliminary given the small sample size of this discovery dataset.
Citation
Hawi , Z , Yates , H , Pinar , A , Johnson , B , Tong , J , Pugsley , K , Dark , C , Pauper , M , Klein , M , Heussler , H S , Hiscock , H , Fornito , A , Tiego , J , Finlay , A , Vance , A , Gill , M , Kent , L S & Bellgrove , M A 2018 , ' A case-control genome-wide association study of ADHD discovers a novel association with the tenascin R ( TNR ) gene ' , Translational Psychiatry , vol. 8 , 284 . https://doi.org/10.1038/s41398-018-0329-x
Publication
Translational Psychiatry
Status
Peer reviewed
DOI
https://doi.org/10.1038/s41398-018-0329-x
ISSN
2158-3188
Type
Journal article
Rights
Copyright the Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Description
This work has been supported by Project Grant funding from the National Health and Medical Research Council (NHMRC) of Australia to Z.H. (1006573, 1002458 and 1065677) and M.A.B. (569636, 1065677, 1045354, 1002458 and 1006573).
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/16732

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