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Exploring the genetic link between RLS and ADHD

Item Type:Article
Title:Exploring the genetic link between RLS and ADHD
Creators Name:Schimmelmann, B.G. and Friedel, S. and Nguyen, T.T. and Sauer, S. and Ganz Vogel, C.I. and Konrad, K. and Wilhelm, C. and Sinzig, J. and Renner, T.J. and Romanos, M. and Palmason, H. and Dempfle, A. and Walitza, S. and Freitag, C. and Meyer, J. and Linder, M. and Schäfer, H. and Warnke, A. and Lesch, K.P. and Herpertz-Dahlmann, B. and Hinney, A. and Hebebrand, J.
Abstract: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 (χ2 = 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.
Keywords:Attention Deficit/Hyperactivity Disorder, RLS, Genome-Wide Association Study
Source:Journal of Psychiatric Research
ISSN:0022-3956
Publisher:Elsevier (The Netherlands)
Volume:43
Number:10
Page Range:941-945
Date:July 2009
Official Publication:https://doi.org/10.1016/j.jpsychires.2009.01.003
PubMed:View item in PubMed

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