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

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.2158-3188Hawi, Ziarih <br />Yates, Hannah <br />Pinar, Ari <br />Orcid: 0000-0002-0064-4215 <br />Arnatkeviciute, Aurina <br />Johnson, Beth <br />Tong, Janette <br />Orcid: 0000-0002-3269-1438 <br />Pugsley, Kealan <br />Dark, Callum <br />Pauper, Marc <br />Klein, Marieke <br />Orcid: 0000-0001-8784-5679 <br />Heussler, Helen S <br />Hiscock, Harriet <br />Fornito, Alex <br />Tiego, Jeggan <br />Finlay, Amy <br />Vance, Alasdair <br />Gill, Michael <br />Orcid: 0000-0003-0206-5337 <br />Kent, Lindsey <br />Bellgrove, Mark A <br />Journal Article <br />Research Support, Non-U.S. Gov't <br />Transl Psychiatry. 2018 Dec 18;8(1):284. doi: 10.1038/s41398-018-0329-x. <br />