Association among attention-deficit hyperactivity disorder, restless legs syndrome, and peripheral iron status: a two-sample Mendelian randomization study

Epidemiological evidence indicates a high correlation and comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and Restless Legs Syndrome (RLS). We aimed to investigate the causal relationship and shared genetic architecture between ADHD and RLS, as well as explore potential causal as...

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Published in:	Frontiers in psychiatry Vol. 15; p. 1310259
Main Authors:	Xiao, Guoqiang, Shi, Hongting, Lan, Qiaoyu, Hu, Jiajia, Guan, Jincheng, Liang, Zhuoji, Zhou, Chumeng, Huang, Zitong, Chen, Yongyuan, Zhou, Borong
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 08-05-2024
Subjects:	ADHD attention deficit hyperactivity disorder iron status Psychiatry restless legs syndrome RLS ADHD attention deficit hyperactivity disorder MR restless legs syndrome RLS LDSC iron status
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Summary:	Epidemiological evidence indicates a high correlation and comorbidity between Attention Deficit Hyperactivity Disorder (ADHD) and Restless Legs Syndrome (RLS). We aimed to investigate the causal relationship and shared genetic architecture between ADHD and RLS, as well as explore potential causal associations between both disorders and peripheral iron status. We performed two-sample Mendelian randomization (MR) analyses using summary statistics from genome-wide meta-analyses of ADHD, RLS, and peripheral iron status (serum iron, ferritin, transferrin saturation, and total iron binding capacity). Additionally, we employed linkage disequilibrium score regression (LDSC) to assess genetic correlations between ADHD and RLS using genetic data. Our MR results supports a causal effect from ADHD (as exposure) to RLS (as outcome) (inverse variance weighted OR = 1.20, 95% CI: 1.08-1.34, p = 0.001). Conversely, we found no a causal association from RLS to ADHD (inverse variance weighted OR = 1.04, 95% CI: 0.99-1.09, p = 0.11). LDSC analysis did not detect a significant genetic correlation between RLS and ADHD (Rg = 0.3, SE = 0.16, p = 0.068). Furthermore, no evidence supported a causal relationship between peripheral iron deficiency and the RLS or ADHD onset. However, RLS may have been associated with a genetic predisposition to reduced serum ferritin levels (OR = 1.20, 95% CI: 1.00-1.04, p = 0.047). This study suggests that ADHD is an independent risk factor for RLS, while RLS may confer a genetic predisposition to reduced serum ferritin levels. The GWAS summary data utilized originated from populations of European ancestry, limiting the generalizability of conclusions to other populations. The potential co-occurrence of RLS in individuals with ADHD should be considered during diagnosis and treatment. Moreover, iron supplementation may be beneficial for alleviating RLS symptoms.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Luigi Francesco Saccaro, University of Geneva, Switzerland Edited by: Li Yang, Peking University Sixth Hospital, China These authors share first authorship Maria Giuseppina Petruzzelli, University of Bari Aldo Moro, Italy
ISSN:	1664-0640 1664-0640
DOI:	10.3389/fpsyt.2024.1310259