A potential association of RNF219‐AS1 with ADHD: Evidence from categorical analysis of clinical phenotypes and from quantitative exploration of executive function and white matter microstructure endophenotypes

Abstract

Aims Attention‐deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder of substantial heritability, yet emerging evidence suggests that key risk variants might reside in the noncoding regions of the genome. Our study explored the association of lncRNAs (long noncoding RNAs) with ADHD as represented at three different phenotypic levels guided by the Research Domain Criteria (RDoC) framework: (i) ADHD caseness and symptom dimension, (ii) executive functions as functional endophenotype, and (iii) potential genetic influence on white matter architecture as brain structural endophenotype. Methods Genotype data of 107 tag single nucleotide polymorphisms (SNP) from 10 candidate lncRNAs were analyzed in 1040 children with ADHD and 630 controls of Chinese Han descent. Executive functions including inhibition and set‐shifting were assessed by STROOP and trail making tests, respectively. Imaging genetic analyses were performed in a subgroup of 33 children with ADHD and 55 controls using fractional anisotropy (FA). Results One SNP rs3908461 polymorphism in RNF219‐AS1 was found to be significantly associated with ADHD caseness: with C‐allele detected as the risk genotype in the allelic model (P = 8.607E‐05) and dominant genotypic model (P = 9.628E‐05). Nominal genotypic effects on inhibition (p = 0.020) and set‐shifting (p = 0.046) were detected. While no direct effect on ADHD core symptoms was detected, mediation analysis suggested that SNP rs3908461 potentially exerted an indirect effect through inhibition function [B = 0.21 (SE = 0.12), 95% CI = 0.02‐0.49]. Imaging genetic analyses detected significant associations between rs3908461 genotypes and FA values in corpus callosum, left superior longitudinal fasciculus, left posterior limb of internal capsule, left posterior thalamic radiate (include optic radiation), and the left anterior corona radiate (P FWE corrected < 0.05). Conclusion Our present study examined the potential roles of lncRNA in genetic etiological of ADHD and provided preliminary evidence in support of the potential RNF219‐AS1 involvement in the pathophysiology of ADHD in line with the RDoC framework.

CircGNB1 drives osteoarthritis pathogenesis by inducing oxidative stress in chondrocytes

“…Importantly, circGNB1 overexpression increased OA severity in the DMM mouse model, whereas circGNB1 silencing had the opposite effect. RNF219 (also known as C13orf7) plays a role in prostate tumors, 47 attention-deficit/hyperactivity disorder 48 and other diseases, 49 although its role in OA remains unclear. In this article, our results indicated that RNF219 expression was up-regulated in the cartilage of the medial tibial plateaus in older patients.…”

Evaluation of the Regulatory Role of Circadian Rhythm Related Long Non-Coding RNAs in ADHD Etiogenesis

“…Studies examining the potential roles of lncRNA in the genetic etiology of ADHD have shown the relationship of the SNP in BC200RNA, RNF219-AS1, STXBP5-AS1 with ADHD. (Arias-Vásquez et al, 2019; Fu, Chen et al, 2021; Kahaei et al, 2020).…”