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Psychiatry Investig. 2017 Nov;14(6):830-838. doi: 10.4306/pi.2017.14.6.830. Epub 2017 Nov 7.

A Genome-Wide Association Study Identifies UTRN Gene Polymorphism for Restless Legs Syndrome in a Korean Population.

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Department of Psychiatry, Korea University College of Medicine, Seoul, Republic of Korea.
Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.
Department of Psychiatry, School of Medicine, Gachon University, Incheon, Republic of Korea.
Department of Psychiatry, Inje University, Ilsan Paik Hospital, Goyang, Republic of Korea.
Department of Neurology, Seoul University College of Medicine, Seoul, Republic of Korea.
Seoul Sleep Center, Seoul, Republic of Korea.
Kosleep Clinic, Seoul, Republic of Korea.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Neurology, Korea University College of Medicine, Seoul, Republic of Korea.



Restless legs syndrome (RLS) is a highly heritable and common neurological sensorimotor disease disturbing sleep. The objective of study was to investigate significant gene for RLS by performing GWA and replication study in a Korean population.


We performed a GWA study for RLS symptom group (n=325) and non-RLS group (n=2,603) from the Korea Genome Epidemiology Study. We subsequently performed a replication study in RLS and normal controls (227 RLS and 229 controls) to confirm the present GWA study findings as well as previous GWA study results.


In the initial GWA study of RLS, we observed an association of rs11645604 (OR=1.531, p=1.18×10-6) in MPHOSPH6 on chromosome 16q23.3, rs1918752 (OR=0.6582, p=1.93×10-6) and rs9390170 (OR=0.6778, p=7.67×10-6) in UTRN on chromosome 6q24. From the replication samples, we found rs9390170 in UTRN (p=0.036) and rs3923809 and rs9296249 in BTBD9 (p=0.045, p=0.046, respectively) were significantly associated with RLS. Moreover, we found the haplotype polymorphisms of rs9357271, rs3923809, and rs9296249 (overall p=5.69×10-18) in BTBD9 was associated with RLS.


From our sequential GWA and replication study, we could hypothesize rs9390170 polymorphism in UTRN is a novel genetic marker for susceptibility to RLS. Regarding with utrophin, which is encoded by UTRN, is preferentially expressed in the neuromuscular synapse and myotendinous junctions, we speculate that utrophin is involved in RLS, particularly related to the neuromuscular aspects.


Genome-wide association study; Replication study; Restless legs syndrome; UTRN; Utrophin

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