A genome-wide association study identifies UTRN gene polymorphism for restless legs syndrome in a Korean population

Chul Hyun Cho; Ji Hye Choi; Seung Gul Kang; Ho-Kyoung Yoon; Young Min Park; Joung Ho Moon; Ki Young Jung; Jin Kyu Han; Hong Bum Shin; Sshyun Ji Noh; Yong Seo Koo; Leen Kim; Hyun Goo Woo; Heon Jeong Lee

doi:10.4306/pi.2017.14.6.830

A genome-wide association study identifies UTRN gene polymorphism for restless legs syndrome in a Korean population

Chul Hyun Cho, Ji Hye Choi, Seung Gul Kang, Ho-Kyoung Yoon, Young Min Park, Joung Ho Moon, Ki Young Jung, Jin Kyu Han, Hong Bum Shin, Sshyun Ji Noh, Yong Seo Koo, Leen Kim, Hyun Goo Woo, Heon Jeong Lee

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Objective 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. Methods 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. 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. Conclusion 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.

Original language	English
Pages (from-to)	830-838
Number of pages	9
Journal	Psychiatry Investigation
Volume	14
Issue number	6
DOIs	https://doi.org/10.4306/pi.2017.14.6.830
Publication status	Published - 2017 Nov

Bibliographical note

Publisher Copyright:
© 2017 Korean Neuropsychiatric Association.

Keywords

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

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.4306/pi.2017.14.6.830

Cite this

Cho, C. H., Choi, J. H., Kang, S. G., Yoon, H.-K., Park, Y. M., Moon, J. H., Jung, K. Y., Han, J. K., Shin, H. B., Noh, S. J., Koo, Y. S., Kim, L., Woo, H. G., & Lee, H. J. (2017). A genome-wide association study identifies UTRN gene polymorphism for restless legs syndrome in a Korean population. Psychiatry Investigation, 14(6), 830-838. https://doi.org/10.4306/pi.2017.14.6.830

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title = "A genome-wide association study identifies UTRN gene polymorphism for restless legs syndrome in a Korean population",

abstract = "Objective 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. Methods 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. 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. Conclusion 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.",

keywords = "Genome-wide association study, Replication study, Restless legs syndrome, UTRN, Utrophin",

author = "Cho, {Chul Hyun} and Choi, {Ji Hye} and Kang, {Seung Gul} and Ho-Kyoung Yoon and Park, {Young Min} and Moon, {Joung Ho} and Jung, {Ki Young} and Han, {Jin Kyu} and Shin, {Hong Bum} and Noh, {Sshyun Ji} and Koo, {Yong Seo} and Leen Kim and Woo, {Hyun Goo} and Lee, {Heon Jeong}",

note = "Publisher Copyright: {\textcopyright} 2017 Korean Neuropsychiatric Association.",

year = "2017",

month = nov,

doi = "10.4306/pi.2017.14.6.830",

language = "English",

volume = "14",

pages = "830--838",

journal = "Psychiatry Investigation",

issn = "1738-3684",

publisher = "Korean Neuropsychiatric Association",

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T1 - A genome-wide association study identifies UTRN gene polymorphism for restless legs syndrome in a Korean population

AU - Cho, Chul Hyun

AU - Choi, Ji Hye

AU - Kang, Seung Gul

AU - Yoon, Ho-Kyoung

AU - Park, Young Min

AU - Moon, Joung Ho

AU - Jung, Ki Young

AU - Han, Jin Kyu

AU - Shin, Hong Bum

AU - Noh, Sshyun Ji

AU - Koo, Yong Seo

AU - Kim, Leen

AU - Woo, Hyun Goo

AU - Lee, Heon Jeong

PY - 2017/11

Y1 - 2017/11

N2 - Objective 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. Methods 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. 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. Conclusion 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.

AB - Objective 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. Methods 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. 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. Conclusion 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.

KW - Genome-wide association study

KW - Replication study

KW - Restless legs syndrome

KW - UTRN

KW - Utrophin

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ER -

A genome-wide association study identifies UTRN gene polymorphism for restless legs syndrome in a Korean population

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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