Exploring the genetic link between RLS and ADHD

Schimmelmann, B G; Friedel, S; Nguyen, T T; Sauer, S; Ganz Vogel, C I; Konrad, K; Wilhelm, C; Sinzig, J; Renner, T J; Romanos, M; Palmason, H; Dempfle, A; Walitza, S; Freitag, C; Meyer, J; Linder, M; Schäfer, H; Warnke, A; Lesch, K P; Herpertz-Dahlman, B; ... (2009). Exploring the genetic link between RLS and ADHD. Journal of psychiatric research, 43(10), pp. 941-5. Amsterdam: Elsevier 10.1016/j.jpsychires.2009.01.003

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Attention deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder of childhood onset. Clinical and biological evidence points to shared common central nervous system (CNS) pathology of ADHD and restless legs syndrome (RLS). It was hypothesized that variants previously found to be associated with RLS in two large genome-wide association studies (GWA), will also be associated with ADHD. SNPs located in MEIS1 (rs2300478), BTBD9 (rs9296249, rs3923809, rs6923737), and MAP2K5 (rs12593813, rs4489954) as well as three SNPs tagging the identified haplotype in MEIS1 (rs6710341, rs12469063, rs4544423) were genotyped in a well characterized German sample of 224 families comprising one or more affected sibs (386 children) and both parents. We found no evidence for preferential transmission of the hypothesized variants to ADHD. Subsequent analyses elicited nominal significant association with haplotypes consisting of the three SNPs in BTBD9 (chi2 = 14.8, df = 7, nominal p = 0.039). According to exploratory post hoc analyses, the major contribution to this finding came from the A-A-A-haplotype with a haplotype-wise nominal p-value of 0.009. However, this result did not withstand correction for multiple testing. In view of our results, RLS risk alleles may have a lower effect on ADHD than on RLS or may not be involved in ADHD. The negative findings may additionally result from genetic heterogeneity of ADHD, i.e. risk alleles for RLS may only be relevant for certain subtypes of ADHD. Genes relevant to RLS remain interesting candidates for ADHD; particularly BTBD9 needs further study, as it has been related to iron storage, a potential pathophysiological link between RLS and certain subtypes of ADHD.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > University Psychiatric Services > University Hospital of Child and Adolescent Psychiatry and Psychotherapy
UniBE Contributor:	Schimmelmann, Benno Karl Edgar
ISSN:	0022-3956
Publisher:	Elsevier
Language:	English
Submitter:	Myriam Pyrlik
Date Deposited:	04 Oct 2013 15:25
Last Modified:	05 Dec 2022 14:26
Publisher DOI:	10.1016/j.jpsychires.2009.01.003
PubMed ID:	19223043
Web of Science ID:	000267906100009
URI:	https://boris.unibe.ch/id/eprint/38496 (FactScience: 221727)