TY  - JOUR
A1  - Spieler, Derek
A1  - Kaffe, Maria
A1  - Knauf, Franziska
A1  - Bessa, José
A1  - Tena, Juan J.
A1  - Giesert, Florian
A1  - Schormair, Barbara
A1  - Tilch, Erik
A1  - Lee, Heekyoung
A1  - Horsch, Marion
A1  - Czamara, Darina
A1  - Karbalai, Nazanin
A1  - von Toerne, Christine
A1  - Waldenberger, Melanie
A1  - Gieger, Christian
A1  - Lichtner, Peter
A1  - Claussnitzer, Melina
A1  - Naumann, Ronald
A1  - Müller-Myhsok, Bertram
A1  - Torres, Miguel
A1  - Garrett, Lillian
A1  - Rozman, Jan
A1  - Klingenspor, Martin
A1  - Gailus-Durner, Valérie
A1  - Fuchs, Helmut
A1  - Hrabě de Angelis, Martin
A1  - Beckers, Johannes
A1  - Hölter, Sabine M.
A1  - Meitinger, Thomas
A1  - Hauck, Stefanie M.
A1  - Laumen, Helmut
A1  - Wurst, Wolfgang
A1  - Casares, Fernando
A1  - Gómez-Skarmeta, Jose Luis
A1  - Winkelmann, Juliane
T1  - Restless Legs Syndrome-associated intronic common variant in Meis1 alters enhancer function in the developing telencephalon
Y1  - 2014/04/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 592 
EP  - 603 
DO  - 10.1101/gr.166751.113 
VL  - 24 
IS  - 4 
UR  - http://genome.cshlp.org/content/24/4/592.abstract 
N2  - 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. 
ER  -