@article{Spieler01042014,
author = {Spieler, Derek and Kaffe, Maria and Knauf, Franziska and Bessa, José and Tena, Juan J. and Giesert, Florian and Schormair, Barbara and Tilch, Erik and Lee, Heekyoung and Horsch, Marion and Czamara, Darina and Karbalai, Nazanin and von Toerne, Christine and Waldenberger, Melanie and Gieger, Christian and Lichtner, Peter and Claussnitzer, Melina and Naumann, Ronald and Müller-Myhsok, Bertram and Torres, Miguel and Garrett, Lillian and Rozman, Jan and Klingenspor, Martin and Gailus-Durner, Valérie and Fuchs, Helmut and Hrabě de Angelis, Martin and Beckers, Johannes and Hölter, Sabine M. and Meitinger, Thomas and Hauck, Stefanie M. and Laumen, Helmut and Wurst, Wolfgang and Casares, Fernando and Gómez-Skarmeta, Jose Luis and Winkelmann, Juliane}, 
title = {Restless Legs Syndrome-associated intronic common variant in Meis1 alters enhancer function in the developing telencephalon},
volume = {24}, 
number = {4}, 
pages = {592-603}, 
year = {2014}, 
doi = {10.1101/gr.166751.113}, 
abstract ={Genome-wide association studies (GWAS) identified the MEIS1 locus for Restless Legs Syndrome (RLS), but causal single nucleotide polymorphisms (SNPs) and their functional relevance remain unknown. This locus contains a large number of highly conserved noncoding regions (HCNRs) potentially functioning as cis-regulatory modules. We analyzed these HCNRs for allele-dependent enhancer activity in zebrafish and mice and found that the risk allele of the lead SNP rs12469063 reduces enhancer activity in the Meis1 expression domain of the murine embryonic ganglionic eminences (GE). CREB1 binds this enhancer and rs12469063 affects its binding in vitro. In addition, MEIS1 target genes suggest a role in the specification of neuronal progenitors in the GE, and heterozygous Meis1-deficient mice exhibit hyperactivity, resembling the RLS phenotype. Thus, in vivo and in vitro analysis of a common SNP with small effect size showed allele-dependent function in the prospective basal ganglia representing the first neurodevelopmental region implicated in RLS.}, 
URL = {http://genome.cshlp.org/content/24/4/592.abstract}, 
eprint = {http://genome.cshlp.org/content/24/4/592.full.pdf+html}, 
journal = {Genome Research} 
}