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.

Evaluating the genetic effects of sex hormone on the development of mental traits: a polygenic score analysis and genome-wide genetic interaction analysis in the UK Biobank cohort

“…To the best of our knowledge, the study involving biological processes of TNR in uid intelligence is still less. Although indirect, our "TNR-Fluid intelligence" GWGIS nding, combined with ndings reported for other psychiatric disorders [37,38,41], supporting the evidence of TNR in the aetiology of psychiatric conditions.…”

“…Interestingly, the TNR gene located within this region (1q25.1-q25.2). Additionally, genome-wide association analysis found a novel association of ADHD and with TNR gene [38]. In another study, researchers found TNR de ciency would cause an early onset and nonprogressive neurodevelopmental disorder [41].…”

Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and genome-wide genetic interaction analysis in UK Biobank cohort

“…To the best of our knowledge, the study involving biological processes of TNR in uid intelligence is still less. Although indirect, the "TNR-fluid intelligence" of GWGIS nding, combined with ndings reported for other psychiatric disorders [37,38,41], supporting the evidence of TNR in the aetiology of psychiatric conditions.…”

LncRNA and transcriptomic analysis of fetal membrane reveal potential targets involved in oligohydramnios

“…It can be inferred that RP11-388P9.2 might affect the CFTR expression by regulating has-miR-114-3p, further affecting the amniotic fluid content of pregnant women. Moreover, TNR can interact with fibronectin 1, which can be involved in cell migration and adhesion biological processes including embryogenesis [ 31 ]. Tenascin is also produced in the extracellular matrix of cultured amnion epithelial cells [ 32 ].…”